Ajog april june 2015 by IJCP

Volume 1, Number 4, 2015

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Asian Journal of

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Volume 1, Number 4, 2015

An IJCP Group Publication Corporate Panel Dr Sanjiv Chopra Prof. of Medicine and Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor Padma Shri, Dr BC Roy & National Science Communication Awardee Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal MD, Group Executive Editor AJOG Specialty Panel

Dr Alka Kriplani Editor Consultant Editor Dr Urmil Sharma Assistant Editors Dr Nutan Agarwal (Delhi) Dr Neera Aggarwal (Delhi) Dr A Biswas (Singapore) Dr CS Dawn (Kolkata) Dr Gauri (Delhi) Dr Suneeta Mittal (Delhi) Dr S Mehra (Delhi) Dr Prashant Mangeshikar (Mumbai) Dr Prakash Trivedi (Mumbai) Dr Gita Ganguly Mukherjee (Kolkata)

Dr (Mrs) Prabha Arora (Delhi) Dr Hema Divakar (Bangalore) Dr Kamini A Rao (Bangalore) Dr Deepti Goswami (Delhi) Dr Neerja Bhatla (Delhi) Dr Bhawna Malhotra (Delhi) Dr Biswas Nicholas (Australia) Dr Sudhaa Sharma (Jammu) Dr Jaibhagwan Sharma (Delhi) Dr Veena Mathur (Agra) Dr Garima Kachhawa

CONTENTS FROM THE ISSUE EDITOR

xxxxxxx 5 Dr Alka Kriplani

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

xxxxxx 6 Dr KK Aggarwal

REVIEW ARTICLE

Prevalence of Microalbuminuria in Patients of HIV/ AIDS and Its Correlation with CD4 Cell Count and the Duration of Illness 7 S Santheev, Lubna Zafar, Anjum Parvez, HS Khan

CASE REPORT

A 28 Weeks Pregnancy with Huge Ovarian Cyst a Rare Case Report 12 Monica Verma, Laxmi Maru, Devyani Tiwari

Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma Dr Kamala Selvaraj

ENT Dr Jasveer Singh

Cardiology Dr Praveen Chandra Dr SK Parashar

Gastroenterology Dr Ajay Kumar

Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses Dr Sidhartha Das Dr A Ramachandran Dr Samith A Shetty

Dentistry Dr KMK Masthan Dr Rajesh Chandna

Dermatology Dr Hasmukh J Shroff Neurology Dr V Nagarajan Journal of Applied Medicine and Surgery Dr SM Rajendran Dr Jayakar Thomas

Anand Gopal Bhatnagar Editorial Anchor Advisory Body Heart Care Foundation of India Non-Resident Indians Chamber of Commerce and Industry World Fellowship of Religions

CLINICAL STUDY

Clinicopathological Study of Ovarian Tumors in A Referral Tertiary Hospital in West Bengal 14 Tamal Kumar Mandal, Barunoday Chakraborty

CASE REPORT

A Rare Case of Ovarian Pregnancy Following Intracytoplasmic Sperm Injection and Embryo Transfer 19 Punhani Ritu, Shankar Kundavi, Thankam R Varma

Programed Labor and Its Effect on Labor Outcome 23 Ruchika Garg, Saroj Singh, Shuchi Rani Agrawal, Meenal Jain

Asian Journal of Volume 1, Number 4, 2015

CONTENTS

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E-219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

CASE REPORT

Rapunzels Syndrome in a Six-Year-Old Child: A Case Report 27

Printed at Crystal Offset, Chennai

Shivanand Reddy KV, Ramesh H

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CASE REPORT

Thyroid and Pregnancy: A Systematic Review

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FROM THE ISSUE EDITOR

Wxxxxxxxxxxxxxx

Dr Alka Kriplani Professor and Head of Unit II Dept. of Obstetrics and Gynecology AIIMS, New Delhi

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Wxxxxxxxxxxxxxxxx

Prof. Dr KK Aggarwal

Padma Shri, Dr BC Roy & National Science Communication Awardee Sr. Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

REVIEW ARTICLE

Prevalence of Microalbuminuria in Patients of HIV/AIDS and Its Correlation with CD4 Cell Count and the Duration of Illness S Santheev*, Lubna Zafar†, Anjum Parvez‡, HS Khan#

ABSTRACT Nephropathy in the form of microalbuminuria and macroalbuminuria is an important cause of morbidity and mortality in HIV/AIDS and is a harbinger of many cardiovascular problems. Present study was conducted over a period of 2 years with the objective to evaluate the prevalence of microalbuminuria in HIV/AIDS patients and its correlation with cluster of differentiation (CD) 4 cell count and the duration of illness. A total of 100 HIV/AIDS patients, attending the antiretroviral therapy (ART) Center of Jawaharlal Nehru Medical College and Hospital (JNMCH), were enrolled. Out of 100 patients 58(58%) were males and 42(42%) were females. Microalbuminuria was observed in 39(39%) patients and significant correlation was found between CD4 cell count (less than 200/mm3) and prevalence of microalbuminuria (p < 0.001). Similarly, statistically significant correlation was observed between the duration of disease and the nephropathy (p < 0.001). Use of microalbuminuria in HIV/ AIDS as a screening test may benefit the patient by early recognition and appropriate intervention. Keywords: Microalbuminuria, HIV/AIDS, CD4 cell count

uman immunodeficiency virus (HIV) is a member of the genus Lentivirus, part of the family of Retroviridae. These are transmitted as single-stranded, positive sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co factors. Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system. Alternatively, the virus may be transcribed, producing new RNA genomes and viral protein that are packaged and released from the cell as new virus particles that begin the replication cycle. Two types of HIV have been characterized: (1) HIV-1 and (2) HIV-2. HIV-1 is the virus that was *Junior Resident - III † Assistant Professor ‡ Assoc. Professor # Professor, Dept. of Medicine, JN Medical College, Aligarh Muslim University, Aligarh. Address for correspondence Dr Anjum Parvez Flat No. 2, II Floor, Royal Apartment, Kela Nagar Civil Lines, Aligarh - 202 001, Uttar Pradesh E-mail: anjumparvez66@yahoo.com

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus type-III (HTLV-III). It is more virulent, more infective and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 compared to HIV-1 implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.1 Presently in India, more than 5 million people are infected with HIV and have the second largest pool of HIV in the world.2 Infection with HIV-1 is associated with a progressive decline in CD4 cell count and an increase in the level of HIV in the blood. The stage of infection can be determined by measuring the patients CD4 cell count and viral load. The stages of HIV infection are acute infection (also known as primary infection), stage of latency and AIDS. Acute Infection

It lasts for several weeks and may include symptoms such as fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, oral and esophageal sores. Stage of Latency

It involves few or no symptoms and can last from 2 weeks to 20 years or more depending on the individual. 7

REVIEW ARTICLE AIDS

Inclusion Criteria

The final stage of HIV infection, is defined by low CD4 cell count (<200/mL), various opportunistic infections, cancers and other conditions.3

HIV patients confirmed by rapid kit enzyme-linked immunosorbent assay (ELISA) and enrolled in ART center, JNMCH, AMU, Aligarh.

Broad spectrum of renal diseases have been reported in patients with HIV/AIDS and ranges from acidbase disorders to acute renal failure, to glomerular diseases such as immunoglobulin (Ig) A nephropathy, membranous nephropathy, membranoproliferative, mesangioproliferative, diffuse proliferative or crescentic glomerulonephritis. Apart from these, a distinctive form of sclerosing glomerulopathy called HIVAN (HIV associated nephropathy) is seen in 5-10% of HIV patients. It may be the most common cause of end-stage renal disease (ESRD) in HIV patients. It is associated with proteinuria, which may be the first manifestation of this condition.4 Among HIV infected patients the presence of proteinuria has been linked to chronic kidney disease, ESRD and new AIDS defining illness and mortality.5 Use of microalbuminuria as a routine screening test is recommended in HIV patients, its use in the screening phase itself can help detection of renal involvement in HIV in early stages and thus reduce patient morbidity and prolong patient survival in a better way. There is scarcity of Indian studies as far as renal spectrum of HIV is concerned and very little data is available on microalbuminuria and proteinuria in HIV patients.

Exclusion Criteria

Aims and Objectives • To study the prevalence of microalbuminuria in HIV/AIDS. • To evaluate the correlation between microalbuminuria and CD4 cell count. • To evaluate the correlation between the microalbuminuria and the duration of disease. Materials and Methods The study was an observational, single center, crosssectional study. It was conducted in 100 HIV/AIDS patients attending the medicine OPD and ART Center, JNMCH, Aligarh Muslim Unversity (AMU), Aligarh. The sampling method used in our study was simple random sampling and the patients entered the study after an informed consent. 8

Patients with fever in past 2 weeks, previous renal disease, acute/chronic urinary tract infection (UTI), diabetes mellitus/hypertension, any history of cardiac ailment, and pregnant females were excluded from the study. Patients with more than 1+ protein in dipstick test were also excluded from the study. Apart from the routine laboratory investigations like haemogram, blood urea, serum creatinine, liver function tests, serum lipid profile, CD4 cell counts, all patients were first screened for proteinuria using urine dipstick method and only those with either nil or trace proteins were selected for further quantification using spot urine Albumin creatinine ratio (ACR) test (modified Jaffe’s reaction). On the basis of spot urine ACR test, patients with 30-300 mg/gm were categorized under microalbuminuria and those with more than 300 mg/gm were labeled as having macroalbuminuria. Study subjects were also categorized on the bases of CD4 cell count into three groups (<200, 200-500 and >500 cells/mm3) as well as on the bases of the duration of illness (<1, 1-5 and >5 years). Statistical Method The data of all the 100 patients enrolled in the study was entered into the SPSS software. Catagoric variables in the study were compared using Pearson's chisquared test (χ2). P value of <0.05 was considered to be significant. Results Out of total 100 patients, 58% were males and 42% females (Table 1). Male to female ratio was 1.4:1. The most common route of transmission was sexual, seen in 56% patients followed by blood transfusion (24%), maternal-fetal transmission (8%) and intravenous (IV) drug abuse (2%) (Table 2). All 100 patients were subjected to urinalysis by spot urine abumin-cratinine ratio (ACR) method for quantification of albuminuria. Thirty-nine percent patients had urine albumin in the range of 30-300 mg/g Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

REVIEW ARTICLE Table 1. Gender-wise Distribution of Patients in Study Group. Sex

No. of patients (n = 100)

Percentage

Male

Female

Total

100

Table 2. Routes of Transmission of HIV in Study Group.

Table 4. Correlation of Microalbuminuria and Macroalbuminuria with CD4 Cell Count. CD4 count

CD4 correlation 30-300 microalbuminuria (%)

>300 macroalbuminuria (%)

Total (%)

<200

4 (10.3)

28 (45.9)

32 (32.0)

200– 500

27 (69.7)

27 (44.3)

54 (54.0)

>500

8 (20.5)

6 (9.8)

14 (14.0)

Total

39 (100)

61 (100)

100 (100)

No. of patients (n = 100)

Percentage

Sexual

Blood transfusion

Mother to child

IV drug abuse

Duration of illness (years)

Others

Route of transmission

Table 3. Prevalence of Microalbuminuria and Macroalbuminuria in Study Group. ACR (albumin-

No. of patients

χ2 = 14.13; df = 2; p = 0.001.

Table 5. Correlation of Microalbuminuria with Duration of Illness.

Percentage

(n = 100)

30-300 (microalbuminuria)

>300 (macroalbuminuria)

Total

100

(microalbuminuria) and rest 61% had urine albumin more than 300 mg/g (macroalbuminuria) (Table 3). Therefore, the prevalence of microalbuminuria in our study was 39%. Microalbuminuria was present in all three groups of CD4 cell count but with varying proportions. It was observed in 4(10.3%), 27(69.7%) and 8(20.5%) patients with CD4 count <200, 200-500 and >500, respectively. Out of 14 (14%) patients of those having CD4 cell counts more than 500, only 6(42.8%) had macroalbuminuria while 8(57.1%) had microalbuminuria. Similarly, out of total 32 patients (32%) who had CD4 cell count less than 200, only 4(12.5%) patients had microalbuminuria and 28(87.5%) had macroalbuminuria (Table 4). Macroalbuminuria indicating more severe degree of renal impairment was seen more in the group with CD4 cell count less than 200/mm3 i.e. more advanced stage of HIV/AIDS and the correlation was found to be statistically significant (p < 0.05). Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Total (%)

30-300 (%)

>300 (%)

7 (17.9)

0 (0.0)

7 (7.0)

1–5

30 (76.9)

52 (85.2)

82 (82.0)

2 (5.1)

9 (14.8)

11 (11.0)

39 (100)

61 (100)

100 (100)

Total

creatinine ratio (mg/gm)

ACR Group

χ2 = 13.154; df = 2; p = 0.001.

Out of 7 patients with duration of illness less than 1 year, all (100%) had microalbuminuria and none had macroalbuminuria. Whereas out of 11 patients who were having disease duration more than 5 years, only 2(18.1%) had microalbuminuria whereas rest 9 (81.8%) had macroalbuminuria, indicating more severe degree of nephropathy in this group (Table 5). This implies that with increase in the duration of disease, severity of nephropathy increases and this correlation was found to be statistically significant (p = <0.05). Discussion The study population comprised of 100 patients, 58(58%) were males and 42(42%) were females. Male to female ratio was 1.4: In a study done by Janakiraman et al6 in Chennai, there were more males than females and male to female ratio was 1.8:1, which is comparable to our study. The routes of transmission in our study population was sexual (56%), followed by blood transfusion (24%). Eight percent got infected by maternal-fetal route, 2% via IV drug abuse and rest 10% got infected through supposedly miscellaneous routes (like tattooing, trauma and surgery). Janakiraman et al also reported heterosexual route to be the commonest mode of transmission. 9

REVIEW ARTICLE

Male Female

20 10

10 Sexual

Blood transfusion

Mother to child

IV drug abuse

Others

20 0

Microalbuminuria

Macroalbuminuria

Figure 3. Prevalence of microalbuminuria in study group.

The patients in our study were evaluated for albuminuria by spot urinary ACR method. Out of total 100 patients 39 patients had ACR in the range of 30-300 mg/ gm, hence the prevalence of microalbuminuria in our study was 39%. There were wide variations observed in the prevalence of microalbuminuria in other studies, ranging from 10% to 33% reported from Port Harcourt (Eke et al)7, Nigeria, Africa and India (Shah, Gupta et al)8. Luke et al9 in a study conducted on 72 HIV positive patients found microalbuminuria in 19.4%. Busch et al10 found a prevalence of 13% among 90 HIV positive patients. Monje et al11 found 19% prevalence of microalbuminuria in 48 HIV seropositive patients in different clinical stages. However, Han T.M et al12 10

200-500

>500

52 30 7

Macroalbuminuria

Microalbuminuria

1 to 5

Figure 5. Correlation of microalbuminuria and macroalbuminuria with duration of illness..

Figure 2. Routes of transmission of HIV.

<200

Figure 4. Correlation of microalbuminuria and macroalbuminuria with CD4 cell count.

Microalbuminuria Macroalbuminuria

Figure 1. Gender-wise distribution of patients in study group.

27 27

found a prevalence of 36% in a cross-sectional study conducted on HIV positive patients in South Africa. This is comparable to our study, the reason may be the similar patient profile in their study like older population, lower CD4 counts, advanced HIV disease and patients not been on any antiretroviral therapy. The reason for wide variation in the prevalence data might be because of varying sample sizes, differing cut off values for the definition of microalbuminuria, differing assay techniques, widely varying study population and selection criteria specifically related to diabetes mellitus and hypertension. The higher prevalence observed in our study group may be attributed to lower CD4 cell counts in majority of patients in our study, thereby reflecting advanced HIV disease, like in the study by Han et al. The patients in our study were divided into three groups according to the CD4 cell counts (<200, 200-500 and >500/mm3), with the purpose of correlating the CD4 status with the presence of microalbuminuria. Out of the 39 patients who had microalbuminuria in our study, 4(10.3%), 27(69.2%) and 8(20.5%) were in less than 200, 200-500 and more than 500 CD4 count groups, respectively. So, it is evident that majority of patients (89.7%) with microalbuminuria belonged to moderate to severe immunosuppression group (CD4 count <500/mm3). Out of total 32 patients with CD4 cell count less than 200, 28(87.5%) had macroalbuminuria and only 4(12.5%) had microalbuminuria. Macroalbuminuria indicating Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

REVIEW ARTICLE more severe degree of renal impairement, was observed more, in less than 200 CD4 count group, i.e., more advanced stage of disease. Thus, nephropathy was seen more at lower CD4 cell counts and late clinical stage of HIV/AIDS and this association was found to be statistically significant. Similar observations were made by Szczech et al 200713 and Janakiraman et al in their respective studies. In our study, patients were divided into three groups on the basis of duration of illness: (1) less than 1 year, (2) 1-5 year and (3) more than 5 year. Out of 7(7%) patients with duration of illness less than 1 year, all had microalbuminuria and none had macroalbuminuria. There were 11(11%) patients with duration of symptoms for more than 5 years, among them only 2(18.2%) had microalbuminuria whereas 9(81.8%) had macroalbuminuria, indicating more severe degree of nephropathy in this group. This indicates that with increasing duration of illness, severity of nephropathy increases and the correlation was found to be statistically significant. Similar observations were made in studies conducted in Port Harcourt, Nigeria by Eke et al and in Tanzania by Fredrick et al.14 Conclusion Nephropathy is an important cause of morbidity and mortality in HIV/AIDS patients. We observed that nephropathy in the form of microalbuminuria and macroalbuminuria was associated with lower CD4 cell count, more advanced stage of HIV/AIDS and increased duration of illness. Use of microalbuminuria as a routine screening test in those who are HIV/AIDS positive will help in uncovering those cases which are heading toward advanced renal impairment. This may help in instituting intensive management strategies to decrease the progression of disease. Further studies need to be done to see for the benefit of angiotensin-converting-enzyme (ACE)-inhibitors and steroids on the progression of microalbuminuria in HIV/AIDS patients. Further studies defining the prognostic significance of microalbuminuria among HIV/AIDS infected patients are also required.

2. Selik RM, Byers RH Jr, Dworkin MS. Trends in diseases reported on US death certificates that mention HIV infection 1987–1999. J Acquir Immune Defic Syndr. 2002; 29(4):378-87. 3. Centre for Disease Control and Prevention. HIV/AIDS Surveillance Report 2005, vol. 17, Atlanta, US. Department of Health and Human Services, Centre for disease Control and Prevention 2007. [online] Available at: http://www. cdc.gov/hiv/topics/surveillance/reports. [Accessed on June, 2015]. 4. Seney FD Jr, Burns DK, Silva FG. Acquired immunodeficiency syndrome and the kidney. Am J Kidney Dis. 1990;16(1):1-13. 5. Szczech LA, Gupta SK, Habash R, Guasch A, Kalayjian R, Appel R, et al. The clinical epidemiological and course of the spectrum of renal diseases associated with HIV infection. Kidney Int. 2004;66(3):1145-52. 6. Janakiraman H, Abraham G, Matthew M, kuruvilla S, Panikar V, Solomon S, et al. Correlation of CD4 counts with renal disease in HIV positive patients. Saudi J Kidney Dis Transpl. 2008;19(4):603-7. 7. Eke FU, Anochie IC, Okpere AN, Eneh AU, Ugwu RO, Ejilemele AA, et al. Microalbuminuria in children with human immunodeficiency virus (HIV) infection in Port Harcourt, Nigeria. Niger J Med. 2010;19(3):298-301. 8. Shah I, Gupta S, Shah DM, Dhabe H, Lala M. Renal manifestations in HIV infected highly active antiretroviral therapy naïve children in India. World J Pediatr. 2012;8(3):252-5. 9. Luke DR, Sarnoski TP, Dennis S. Incidence of microalbuminuria in ambulatory patients with acquired immunodeficiency syndrome. Clin Nephrol. 1992;38(2):69-74. 10. Busch HW, Riechmann S, Heyen P, Heidenreich S, Kaufmann CC, Rahn KH, et al. Albuminuria in HIV infected patients. AIDS Res Hum Retroviruses. 1994;10(6):717-20. 11. Monge AL, Bortolozzi R, Sosa V. Microalbuminuria in patients of HIV (positive) and its relationship with immunologic and viral markers. Presented at the XI International Conference on AIDS. British Columbia: Vancouver; 1996. pp. 394-9. 12. Han TM, Naicker S, Ramdial PK, Assounga AG. A cross sectional study of HIV–seropositive patients with varying degrees of proteinuria in South Africa. Kidney Int. 2006;69(12):2243-50.

References

13. Szczech LA, Grunfeld C, Scherzer R, Canchola JA, van der Horst C, Sidney S, et al. Microalbuminuria in HIV infection. AIDS. 2007;21(8):1003-9.

1. Gilbert PB, McKeague IW, Eisen G, Mullins C, GuéyeNDiaye A, Mboup S, et al. Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal. Stat Med. 2003;22(4):573-93.

14. Fredrick F, Ruggajo P, Maro EE, Iversen BM, Basu G. Renal manifestations and associated factors among HIV infected children at Muhimbili National Hospital, Dares Salaam, Tanzania. BMC Infect Dis. 2012;12(Suppl 1):011. Sexual

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT

A 28 Weeks Pregnancy with Huge Ovarian Cyst a Rare Case Report Monica Verma*, Laxmi Maru†, Devyani Tiwari‡

ABSTRACT The xxxxxxxxxxx

Keywords: Hxxxxxxxxxxxxxx

he presence of ovarian cyst in pregnancy is unusual with prevalence of around 1-2% and the incidence of malignancy being 1-3%. Such masses rarely grow beyond 5 cm and by the second trimester are also not commonly found. Such ovarian tumors are left for conservative management unless they show signs of malignancy or grow to sizes as big as to prevent the growth of the baby. We present a case of a healthy 28 week pregnancy with a huge 15 kg ovarian cyst which was managed by a laprotomy followed by tocolytics.

Case Report A 30-year-old women third gravida with previous one section with one vaginal birth after cesarean (VBAC) presented to us in the emergency. Being third gravida she knew that her abdomen was growing very fast. She presumed to have been carrying two babies. She went for her first antenatal visit in her fifth month *Assistant professor † Professor and HOD ‡ Resident doctor Dept. of Obstetrics and Gynaecology MGMMC & MYH, Indore Address for correspondence Dr Monica Verma Department of Obstetrics and Gynaecology MGMMC & MYH, Indore - 452 001 E-mail: mv27sep@gmail.com

of pregnancy in the periphery where an ultrasound was done and an ovarian cyst was diagnosed. She was refered to us with this finding. She was very apprehensive toward the diagnosis and fear associated of it being a malignancy. The patient reported to us only at 7th month. She presented with overdistended abdomen of 36 week size and a cystic mass felt. Uterus was not felt and no fetal parts or fetal heart sounds were heard. A sonography was repeated and it showed a huge mass of the ovary with solid and cystic components and strong possibility of neoplasia. The baby was though healthy of 28 weeks with no abnormality. After correcting the anemia patient was taken up for laprotomy under gestational age (GA). Huge ovarian cyst of 40* 40* 15 cm was present on the right side with a normal uterus. The left ovary also appeared polycystic. The right ovary appeared to be benign on gross inspection. It was removed completely without rupturing it. On weighing, it was found to be of around 15 kg. The left ovary was aspirated and clear fluid of around 100 mL was removed. It was left in situ. The specimen ruptured spontaneously because of the thin and papery wall and the material inside it was sticky and slimy like a mucinous one. The patient was managed with duvadilan and progesterone to prevent preterm labor. The postoperative period of the patient went uneventful with both mother and baby in good health. The uterine fundal height was now corresponding to that of 28 weeks. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT The histopath showed serous cystadenoma of the ovary. The patient delivered at 40 wk vaginally. She had spontaneous labor and delivered a healthy but intrauterine growth rustriction (IUGR) child weighing 2 kg. Discussion Finding ovarian cyst in pregnancy is not an extreme rarity. After 16 weeks frequency of ovarian cyst is reported between 0.5% and 3.0%.1 Such cysts do increase with pregnancy but cysts taking such large sizes is very unusual. Functional cysts are the most common ovarian tumors diagnosed in pregnancy. These ovarian cysts carry the risk of torsion, hemorrhage, malignancy, early pregnancy losses, intrauterine growth restriction and also preterm labor. An ultrasound is quite accurate for the detection and assessment of risk of malignancy. Morphological criteria are more accurate for identification of benign cyst than malignant mass. It should be the first imaging modality of investigation for ovarian mass in pregnant or nonpregnant women.2 Expectant management is recommended for most pregnant patients with asymptomatic, nonsuspicious cystic masses. Surgical intervention during pregnancy is indicated for large or symptomatic tumors and those that appear highly suspicious for malignancy on imaging.3 Large cyst like our patient can prevent growth of the baby and give discomfort to the mother in the form of respiratory and heart function compromise. If it ruptured inside the abdomen could also cause pseudomyxoma peritonei. A timely laprotomy multiplied the chances of a good fetal outcome and also prevented from the risk of prematurity. The extent of surgery depends on the intraoperative diagnosis

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

of a benign versus malignant tumor. We opted for a conservative approach in the form of oopherectomy as it clearly appeared a benign ovarian tumor. The other ovary also showed polycystic appearance which explained the condition and tendency. There have not been many case reports of such advanced pregnancy with an ovarian cyst of 15 kg. There have been case reports from Haldwani Uttrakhand4 and Pakistan5 Both patients were multigravidas and had healthy pregnancies. Conclusion Ovarian cysts in pregnancy must be managed conservatively unless an ultrasound suggests malignancy. Majority of ovarian cysts are functional and resolve spontaneously by the second trimester. Finding huge ovarian cyst like in our patient is a rarity. It affected the growth of the ongoing pregnancy causing intrauterine growth restriction. But, the surgical intervention prevented many more foreseen complications to both the mother and the baby. References 1. Goffinet F. Ovarian cysts and pregnancy. J Gynecol Obstet Biol Reprod (Paris). 2001;30(1 Suppl):S100-8. 2. Valentine L. Use of morphology to characterise and manage common adnexal masses. Best Pract Res Clin Obstet Gynaecol. 2004;18(1)71-89. 3. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol. 2007;110(1):201-14. 4. Pandey N, Chauhan P, Rawat U, Jain G. Huge mucinous cystadenoma complicating third trimester with previous two caesarean. Acta Medica International. 2014;1(1):43-5. 5. Noreen H, Syed S, Chaudhri R, Kahloon LE. A large unilocular mucinous cystadenoma in third trimester. J Coll Physicians Surg Pak. 2011;21(7):426-8.

CLINICAL STUDY

Clinicopathological Study of Ovarian Tumors in a Referral Tertiary Hospital in West Bengal Tamal Kumar Mandal*, Barunoday Chakrabortyâ&#x20AC;

ABSTRACT Introduction: Ovarian tumors account for fifth most common cause of cancer-related deaths in women worldwide. It accounts for 6% of all cancers among women. Though it is one of the treatable cancers due to its sensitivity to different modalities of anticancer therapy, it frequently does not result in symptoms until it becomes an advanced disease. Objectives: To study the incidence, histopathological spectrum and clinical correlates of ovarian tumors at a tertiary care teaching hospital. Methods: A study was undertaken during a period of 1 year (1st Jan 2014 to 31st Dec 2014). The tumors were classified according to World Health Organization (WHO) classification after thorough examination of hematoxylin and eosin (H&E) slides. Data on clinical presentation were recorded in each case. Results: There were a total of 107 cases. Surface epithelial tumors (SET) emerged as the commonest variety accounting for 57.01%, followed by germ cell tumors (GCT) (23.36%). Sex cord stromal tumors (SCST) (0.93%) and metastatic tumors accounted for 1.87%. The age range was 8-70 years. Metastatic tumors involved younger age groups. Abdominal mass was the commonest clinical presentation followed by pain abdomen. Conclusion: Ovarian tumor were found to occur in wide range of ages (8-70 years) with abdominal mass and pain abdomen being the commonest clinical presentation. SET and GCT together constitute the majority of the cases (80.37%). An accurate histological diagnosis and staging are the factors therapeutically and prognostically important. Keywords: Surface epithelial tumors, germ cell tumors, sex-cord stromal tumors, borderline tumor, functional cysts

varian tumors include wide spectrum of neoplasms involving epithelial tissue, connective tissue, specialized hormone secreting cells, germinal and embroyonal cells.1 These are treatable tumors because of sensitivity to anticancer therapies.2 It accounts for 6% of total cancers among women and is the 5th most common form of cancerrelated deaths among women worldwide and almost half of the deaths due to gynecological cancers. The disease has highest fatality-to-case ratio among all the gynecologic cancers.2 The risk of developing ovarian cancer is highest around the age of 55 years. The benign tumors mostly occur in young women between ages of 20 and 45 whereas the malignant tumors are common in older women between ages of 40 and 65. The incidence is high in postmenopausal women, unmarried women

*RMO cum Clinical Tutor â&#x20AC; Associate Professor Dept. of Gynaecology and Obstetrics Bankura Sammilani Medical College, Bankura, West Bengal, India Address for correspondence Dxxxxxxxxxxxxx

or in married women with low parity.3 It is estimated that about 1 in every 70 women have a life-time risk of developing ovarian cancer. Unfortunately, the survival rate is <50% because of a lack of sensitive and specific screening test and asymptomatic presentation of the cases till an advanced stage.4 It is important to determine the histopathological pattern of ovarian tumors from a diagnostic as well as prognostic point of view. The aim of this study was to study the incidence, histopathological spectrum and clinical correlates of ovarian tumors. Materials and Methods This is a retrospective study done in the Department of Obstetrics and Gynecology of Bankura Sammilani Medical College, Bankura, West Bengal from 1st January 2014 to 31st December 2014. All the cases of ovarian tumors operated during that period were included in this study. Data including age, clinical presentation, related history, involvement (unilateral or bilateral) were obtained from the butylated hydroxytoluene (BHT). Gross findings of all cases were also noted from the operation theater (OT) note and biopsy report. Histopathology reports of all the cases were recorded from the data base. hematoxylin Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CLINICAL STUDY and eosin (H & E) stained slides of each case were studied. The tumors were classified according to the WHO classification of ovarian tumors.5 Results A total of 107 ovarian tumors were operated in the study period. Amongst them, 83(77.57%) were benign, 1(0.93%) was borderline while 23(21.50%) were malignant (Table 2 and Fig. 2). Surface epithelial tumor was the most common class of tumor and seen in 61(57.01%) cases, followed by germ cell tumors seen in 25(23.36%) cases (Table 1 and Fig. 1). Of the 83 benign tumors, 42(50.60%) were surface epithelial tumors while 22(26.51%) were germ cell tumors. Out of the 23 malignant tumors, 18(78.26%) were surface epithelial tumors while 3(13.04%) were of germ cell origin (Table 2). Out of the 61 surface epithelial tumors, 42(68.85%) were benign, 1(1.64%) was borderline whereas 18(29.51%)

Table 2. Histological Pattern of Ovarian Tumors Diagnosis

Benign Borderline Malignant

Total

Surface epithelial tumor (SET)

Serous tumor

Mucinous tumor

Clear cell carcinoma

Endometrioid tumor

Malignant Brenner tumor

Germ cell tumor (GCT)

Mature cystic teratoma/dermoid cyst

Mixed germ cell tumor (dysgerminoma + yolk sac)

Mixed germ cell tumor (dermoid + mucinous cystadenoma)

Dysgerminoma

Yolk sac tumor

Table 1. Frequency of Different Classes of Ovarian Tumors

Sex cord-stromal tumor (SCST)

Classes of tumor

Fibroma

Secondary (metastatic) tumor

No. of cases

Surface epithelial tumor (SET)

57.01

Germ cell tumor (GCT)

23.36

Sex cord-stromal tumor (SCST)

0.93

Secondary (metastatic) tumor

1.87

Functional cysts

16.82

Total

107

100

Function cysts

Follicular cyst

Corpus luteal cyst

Chocolate cyst

Grand total

107

Krukenberg tumor

SET GCT SCST Secondary Functional cyst

were malignant. Most of these tumors were of serous and mucinous in origin and were seen in 43(70.49%) and 15(24.59%) cases, respectively (Table 2). Out of the 25 germ cell tumors, 22(88%) were benign, most being mature cystic teratoma (95.45%). Dysgerminoma and yolk sac tumor were the common germ cell malignancy.

Figure 1. Frequency of different classes of ovarian tumors

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Fibroma was the only SCST in our study which was benign. 15

REVIEW ARTICLE Approximately, 59(55.14%) tumors were seen in the 20-40 year age group (Table 3 and Fig. 3). Benign tumors were more common than malignancies in all age groups. Most benign tumors 50/83 (60.24%) were diagnosed in the 3rd and 4th decades of life, whereas most malignant tumors 21/23(91.30%) were seen in 3rd decade onward, with the exception of malignant germ cell tumors which were mostly seen below the age of 20. The only borderline tumor was seen at the age of 14 (Table 3).

Benign Borderline Malignant

Commonest clinical presentation was distension of abdomen and lower abdominal mass followed by pain abdomen. Irregular bleeding per vagina was seen in 12 cases. Ascites and urinary symptoms were seen in 3 malignant cases. Loss of weight was a common presentation of malignant tumors comprising of 8 cases. Symptoms related to torsion were seen in 17 cases and one incidental finding of ovarian tumor in patient who presented with subacute intestinal obstruction and surgical help was called for during laparotomy. Pregnancy was associated with 4 cases among which 2 were of serous cyst adenoma and 2 of mature cystic teratoma.

Figure 2. Frequency of different categories of ovarian tumors

Overall, serous cyst adenoma was the most common benign type and was seen in 33/83(39.76%) cases. Only one case of borderline tumor was found in our study which was mucinous in type. Serous carcinoma was the most common malignancy and seen in 10/23(43.48%) patients (Table 2). Metastatic tumor constituted 2 cases (1.87%), all of them were Krukenberg tumors.

Gross examination of the specimens revealed that majority of the tumors were cystic (44.5%) followed by solid (13.2%) and mixed (42%). In the benign group, majority of the cases (42.1%) were cystic, 4.8% solid and 32.5% were mixed. The borderline tumor was cystic grossly. In malignant group both solid and mixed, tumors were almost equal. Unilateral tumors were observed in 84(78.5%) cases. Involvement of left ovary (65%) was more common than the right (35%). Bilaterality was seen in 23 cases (21.50%).

Out of the 107 cases of ovarian tumors, 18(20.56%) cases were functional cysts (hemorrhagic corpus luteal cyst, follicular cyst, endometriotic cysts). The age distribution of the cases ranged from 8 to 70 years with a median age of 35.39 year. The youngest patient (8-year-old girl) presented with benign cystic teratoma and the oldest patient (70-year-old woman) with benign serous cyst adenoma.

Table 3. Frequency of Different Classes of Ovarian Tumors in Different Age Group Classes of tumor Surface epithelial (n = 61)

Total

Types

<20

20-29

30-39

40-49

50-59

â&#x2030;Ľ60

Total

Benign

Borderline

Malignant

Benign

Germ cell (n = 25)

Malignant

Sex-cord stromal (n = 1)

Benign

Secondary (n = 2)

Malignant

Functional cyst (n = 18)

Benign

Total (n = 107)

107

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

REVIEW ARTICLE 35

No. of tumors

30 25 20 15 10 5 0

<20

20-29

30-39

40-49

50-59

Age

In agreement with other studies, most ovarian tumors were seen in the reproductive age group, between 20 and 40 years.17,18 Benign tumors were found in all age groups. Malignant surface epithelial tumors occurred mostly in the 4th decade onward. Similar observations were also made in other studies.19,20 In patients under the age of 30 years, approximately 21/46(45.65%) of the ovarian tumors are of germ cell origin and accounting for two-thirds of ovarian cancers (3 out of 5).21

Discussion

Unilateral (78.5%) involvement was more common than bilateral (21.5%) coinciding with the findings of other studies.12,22

Ovarian tumors has become increasingly important because of its large variety of histomorphological patterns and a high mortality rate.1 The incidence, clinical appearance and the behavior is extremely variable. It is impossible to diagnose the nature of the ovarian tumor preoperatively just by clinical examination, ultrasound and even by an fine-needle aspiration cytology (FNAC) and hence an early exploration followed by staging and optimal debulking and biopsy of the excised tissue is the gold standard of management.6

Majority were grossly cystic 44.5% followed by solid and mixed tumors. Majority of benign groups, were cystic 42.1%. In malignant group, solid and mixed tumors were common. This goes in agreement with findings of Fusey et al who reported that most of the cystic swellings were either benign or nonneoplastic while almost all solid and mixed tumors were malignant.23 Chhanda et al in a 10 years study of ovarian tumors revealed that in the benign group majority of the cases were cystic (86.7%). While in malignant group majority cases (69.2%) were solid.24

A total of 107 cases were documented, out of which 77.57% were benign tumors, 0.93% was borderline and 21.50% were malignant tumors. Similar results were seen in studies by Pilli et al and Nowak et al where incidence of benign, borderline and malignant ovarian tumor comprised of 75.2, 2.8, 21.9 and 79.5, 2.1, 18.4%, respectively.7,8

The most common presentation was abdominal mass with or without distension and pain. This is in agreement with majority of studies.6,23,25,26

Figure 3. Frequency of ovarian tumors in different age group.

Epithelial tumors were predominant (50.60%) among the benign group followed by germ cell tumors (26.51%). Serous cyst adenoma were found to be more common than mucinous cyst adenoma in our study. This compares well with studies by Swamy and Prabhakar et al.9,10 In our study, mature cystic teratoma (95.45%) was the commonest type of germ cell tumour. In a study by Yasmin et al, mature cystic teratomas were the 2nd commonest after serous cystadenoma.11 The commonest malignant tumor in this series were of surface epithelial tumor (78.26%). This finding is similar to findings of Shy et al and Di et al.12,13 In this study, serous cystadenocarcinoma constituted the most common malignant variety (43.48%) as shown by various other studies.14-16 Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Conclusion Though ovarian cyst and tumor can be diagnosed clinically, origin and nature of the tumors cannot be determined clinically. Histopathological examination of the ovarian tumor is a must to find out the origin and the nature of the tumor. Benign tumors can be safely removed by surgery and malignant tumors are managed according to the type, grading and stage of the tumor. Clinical evaluation, radiological evaluation and histopathological examination are important in the management of the ovarian tumors. The combined efforts of gynecologist, radiologist, oncologist and pathologist will not only hit the right diagnosis but also track the patient to the right path of management. This study has shown occurrence of younger age groups in the primary malignant ovarian tumors and the metastatic tumors also. Hence, this study emphasizes that in a young women with ovarian mass, possibility 17

REVIEW ARTICLE of malignancy and metastatic tumors should not be underestimated. References 1. Padubidri VG. Howkins and Bourne Shaw's textbook of gynaecology. Textbook of Gynaecology, 13th Edition. New Delhi: Elsevier; 2008. 2. Berek JS, Thomas GM. Ovarian cancer. Practical Gynaecologic Oncology, 3rd Edition. Lippincott Williams & Wilkins; 2000. 3. Crum CP. The Female Genital Tract. In: Cotran RS, Kumar V, Collins (Eds.). Pathologic Basis of Disease, 7th Edition. Philadelphia: Elsevier; 2004. pp. 1092-104. 4. Rosai J. Ovary. In: Rosai and Ackerman’s 9th Edition. Missouri: Elsevier; 2004. 5. WHO Classification of Tumors. Pathology and genetics. In: Tavasolli FA, Devilee P (Eds.). Tumors of Breast and Female Genital Organs, 7th Edition. Lyon: IARC Press; 2003. p. 114. 6. Bhattacharya M, Shinde SD, Purandare VN. A clinicopathological analysis of 270 ovarian tumors. J Postgrad Med. 1980;26(2):103-7. 7. Pilli GS, Suneeta KP, Dhaded AV, Yenni VV. Ovarian tumors: a study of 282 cases. J Indian Med Assoc. 2002;100(7):420, 423-4, 447. 8. Nowak M, Szpakowski M, Malinowski A, Romanowicz H, Wieczorek A, Szpakowski A, et al. Ovarian tumors in the reproductive age group. Ginekol Pol. 2002;73(4):354-8. 9. Swamy GG, Satyanarayana N. Clinicopathogical analysis of ovarian tumors – a study on five years samples. Nepal Med Coll J. 2010;12 (4):221-23. 10. Prabhakar BR, Maingi K. Ovarian tumors – prevalence in Punjab. Indian J Pathol Microbiol. 1989;32(4):276-81. 11. Yasmin S, Yasmin A, Mohammad Asif. Clinicohistological pattern of ovarian tumors in Peshawar region. J Ayub Med Coll Abbottabad. 2008;20(4):11-13.

12. Shy Y. Histological classification in 10,288 cases of ovarian malignant tumors in China. Zhinghua Fu Chan Ke Za Zhi. 2002;37(2):97-100. 13. Di Bonito L, Patriarca S, Ovarian tumors. Eur J Gynaecol Oncol. 1988;9(4):324-30. 14. Sarkar R. Ovarian neoplasm: a 14 years study. Journal of O&G. 1996;156-9. 15. Ahmad Z, Kayani N, Hasan. Histological pattern of ovarian neoplasm. J Pak Med Assoc. 2000;50(12):416-9. 16. Levi F, Franceschi S, Epidemiologic pathology of ovarian cancer. Ann Oncol. 1993;4(4):289-94. 17. Jha R, Karki S. Histological pattern of ovarian tumors and their age distribution. Nepal Med Coll J. 2008;10:81-5. 18. Khan AA, Luqman M, Jamal S, Mamoon N, Mushtaq S. Clinicopathological analysis of ovarian tumors. Pak J Pathol. 2005;16:28-32. 19. Scully RE, Young RH, Clement PB (Eds.). Tumors of the ovary, maldeveloped gonads, fallopian tube and broad ligament. Atlas of Tumor Pathology, 3rd series. Washington, D.C: Fascicle 23, Armed Forces Institute of Pathology; 1999. 20. Amatya S, Gurung G, Rana A. Annual clinicopathological analysis of ovarian tumors at TUTH. NJOG. 2010;4:18-24. 21. Lack EE, Goldstein DP. Primary ovarian tumors in childhood and adolescence. Current Prob Obstet Gynecol. 1984;7:8. 22. Kaku T, Ogawa S, Kawano Y, Ohishi Y, Kobayashi H, Hirakawa T, et al. Histological classification of ovarian cancer. Med Electon Microsc. 2003;36(1):9-17. 23. Fusey SS, Wairagade SR. Ovarian tumors in teenage. JOGI. 1992;118-21. 24. Chhanda M, Dasgupta A, Ghosh RN, Sengupta J. Ovarian tumors: a ten year study. JOGI. 1990:691-5. 25. Tyagi SP, Maheswari V, Tyagi N, Solid tumors of the ovary. J Indian Med Assoc. 1993;91(9):227-30. 26. Oumachigui A, Narasimhan KL. Ovarian tumors in children. JOGI. 1989;441-5.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT

A Rare Case of Ovarian Pregnancy Following Intracytoplasmic Sperm Injection and Embryo Transfer Punhani Ritu, Shankar Kundavi, Thankam R Varma

ABSTRACT Ovarian pregnancy after in vitro fertilization (IVF) is rare and can be easily missed unless there is a high index of suspicion. Preservation of ovarian tissue during surgery is of utmost importance especially in subfertility patients, where the goal is to preserve the fertility. We present a case of ovarian pregnancy who had a successful intracytoplasmic sperm injection (ICSI) conception after preserving the ovary. Keywords: Hxxxxxxxxxxxxxx

varian pregnancy is a rare form of the nontubal ectopic pregnancy.1 It ends with rupture before the end of the first trimester.2 The incidence of primary ovarian pregnancy is 3.3% of all ectopic pregnancies,3 and the incidence reported following IVF-embryo transfer (IVF-ET) is 0.27% per clinical pregnancy.4

We report a case of primary ovarian pregnancy following ICSI for primary infertility treatment. The case reported here is interesting because of its rarity and the successful outcome of ICSI after preserving the ovary.

An increased incidence of ectopic pregnancies up to 5% after IVF and ET is a well-known phenomenon.5,6 Hence, the first pregnancy achieved by IVF-resulted in an ectopic pregnancy in 1976.7 However, primary ovarian pregnancy is a rare phenomenon following natural conception or IVF-ET; twin ovarian pregnancy is extremely rare.

She was 31 years primary subfertility patient, married since 3 years, and had regular cycles. She was diagnosed to have stage 4 endometriosis 1 year back and was referred to our institute for IVF. She also had a septal resection prior to coming to our unit.

In spite of advances in clinical sciences, diagnosis of ovarian ectopic is rarely made before the surgery. With few exceptions, the initial diagnosis is made on the operating table and the final diagnosis only on histopathology on the basis of the four Spiegelbergâ&#x20AC;&#x2122;s criteria, establishing that the pregnancy is limited to the ovary and does not involve the tube.8 Because initial diagnosis in ovarian pregnancy is difficult, many of these cases will be diagnosed as possible tubal pregnancies only.9 *Sxxxxxxxxxxxxxx

Address for correspondence Institute of Reproductive Medicine and Womens Health Madras Medical Mission, Chennai - 600 037, India.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

Case Report

After her basic evaluation, she underwent controlled ovarian stimulation with ultra long protocol for controlled ovarian stimulation, for total 10 days, and triggered her with injection human chorionic gonadotropin (HCG) 10,000 units, 35 hrs following which oocyte retrieval was done, and 4 mature M2 oocytes were collected. Four grade A embryos were transferred on day 3, under ultrasound guidance. She was given full luteal support, and the b-HCG done on the 16th day following ET, was 839 mIU/mL. The subsequent b-HCG value which was done 1 week later, was found to be about 15,099 mIU/mL. The ultrasound done on the same day, at 5 weeks and 6 days of gestation showed? Ectopic gestation of the left adnexa, with normal sized uterus and normal appearing right adnexa. Second expert opinion for ultrasound was taken and the reported was suggestive of a left adnexal mass, with a yolk sac, but no fetal pole. As the patient was hemodynamically stable, a plan for medical management was made. 19

CASE REPORT Inj. methotrexate 75 mg IM (intramuscular) was given and after 4 days the repeat b-HCG was 19,900. We repeated the ultrasound on that day, and to our surprise we found a live twin ectopic gestation. Thus, patient was taken up for emergency operative laparoscopy. Three port laparoscopy was done, uterus appeared normal, right ovary was adherent to the back of the uterus, right tube appeared dilated and unhealthy. Omental adhesions were also found and adhesiolysis was done. Left ovary was only partially seen and was adherent to the lateral pelvic wall. As ectopic gestation could not be clearly visualized, we proceeded with the laparotomy after taking the consent. Both the ovaries were dissected free. Bleeding from the left ovary seen and hemorrhagic material was removed and sent for his to pathological examination (HPE). Right ovary was apparently normal. Few hemostatic sutures were taken on the left ovary. B/L salpingectomy was done as both the tubes appeared unhealthy.

Figure 1. H&E-40X chorionic villi surrounded by ovarian tissue

His topathology report was consistent with left ovarian ectopic, both the tubes did not show any evidence of chorionic villi (Figs. 1 to 3). She had ICSI twice later and oocytes were retrieved only from the left ovary, due to inaccessibility of the right ovary. She conceived in the second attempt and delivered a healthy girl baby.

Figure 2. H&E-100X chorionic villi

Discussion Ovarian pregnancy is an uncommon form of ectopic pregnancy. The first case of ovarian pregnancy was reported by St. Maurice in 1689. Marcus and Brinsden reported an incidence of 6% following IVF-ET following 135 ectopic.10 But, the incidence following natural conception is much lower, ranging from 1/16,000 to 1/1,500 deliveries accounting for 3.3% of all ectopic pregnancies. Rarely ovarian pregnancy can be a part of heterotopic or of a twin ovarian pregnancy. The four Spiegelberg's criteria for ovarian ectopic gestation are: (1) fallopian tubes including fimbria must be intact and separate from the ovary; (2) the pregnancy must occupy the normal position of the ovary; (3) the ovary must be attached to the uterus through the utero-ovarian ligament and (4) there must be ovarian tissue attached to the pregnancy in the specimen.11 Our case met all the diagnostic criteria for ovarian pregnancy. 20

Figure 3. H&E-100X ovarian tissue showing decidualization

Ovarian pregnancy following IVF is a rare entity. With intensive review of literature, very few case reports were found.12-14 The cause for development of an ovarian pregnancy is a result of secondary implantation or failure of follicular extrusion. In the case, we have Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT described, the exact mechanisms of ovarian pregnancy after ICSI are not very clear. The presence of tubal pathology and pelvic inflammatory disease could be predisposing factors as with tubal pregnancies. One of the predisposing factors for ectopic pregnancy in this case could be endometriosis, and second factor could be transfer of four embryos. One of the most likely probabilities is reverse migration of one of these embryos toward the fallopian tube and implantation in the ovary.15 This unusual event could also be the result of the volume and pressure of culture medium injected during ET. Another contributory factor in the pathogenesis could be head tilted down position after the ET, which was not done in our case. Knutzen introduced the reverse migration concept and demonstrated the fate of embryos “in utero” by observing that radiopaque dye could enter the fallopian tubes in 38.2% of the patients easily after a mock ET.16 When an ectopic pregnancy occurs after assisted reproductive technology (ART), it is mostly a result of uterine contractions, which cause the carefully placed embryos to be ejected into the fallopian tube. Various strategies to reduce the risk of this occurring are typically employed. The use of ultrasound guidance to place embryos and the use of minimal fluid to transfer them helps. There is some evidence that transferring blastocysts that are ready to implant instead of earlier embryos may also reduce the incidence. Sometimes, however, despite the best-laid plans, ectopic pregnancies do occur.17 Difficult embryo transfer may be another possible factor due to resulting in additional stimulation of junctional zone contractions which increases the risk of ectopic pregnancy. Lesny et al showed that a difficult ET stimulates junctional zone contractions and that strong endometrial waves in the fundal area of uterus could move mock embryos into the fallopian tubes. They also noted that manipulation with tissue forceps, for the purpose of facilitating ET, could affect uterine contractility18 but such events were not encountered at the time of embryo replacement in our patient. Reverse migration of an embryo also could be due to high estrogen levels after ovarian stimulation.19 In our case, serum estradiol concentration was 1,656 pg/mL on the day of HCG injection. 20 μL of the media was used and the ET was smooth and it was done under ultrasound guidance. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

There are very few reports of an accurate preoperative diagnosis, utilizing sonography. Ovarian pregnancy on ultrasound is typically described as a wide echogenic ring with a small internal echolucent area on the surface or within the substance of the ovary, the echogenicity of the ring usually being greater than the ovary.20 A high degree of suspicion is needed, particularly in stimulated ovaries, wherein it can easily be mistaken for hemorrhagic corpora lutea. Doppler ultrasonography (USG) seems to offer little additional diagnostic value due to the high vascularity of the ovary.20 In our case, we could identify the ovarian pregnancy only after the histopathology report. The correct diagnosis is mostly made at the surgery and requires histopathological confirmation. Diagnosis of ovarian pregnancy should be suspected from elevated b-HCG, lack of intrauterine gestation, a complex ovarian mass on USG, patient’s risk factors, in addition to the Spiegelberg criteria. Patients most often undergo surgery for suspected tubal ectopic pregnancy or hemorrhagic corpus luteum. Diagnosis of primary ovarian pregnancy is very difficult because of the rarity and the asymptomatic nature before rupture. Although the combination of serum β-HCG and transvaginal sonography increases the diagnostic accuracy of ectopic pregnancy, the diagnosis of ovarian pregnancy depends on the physicians suspicion and experience. Treatment of almost all known ovarian ectopic pregnancies has been surgical. Also case reports have described successful medical management with methotrexate.21 The most common surgical treatment for unruptured ovarian pregnancy is either ovarian wedge resection or oophorectomy,22,23 either laparoscopic or via minilaparotomy. The outcome of subsequent pregnancy is successful, with a low incidence of subsequent ectopic pregnancy after the ovarian pregnancy is treated be surgery.24 Our patient was taken for ovarian wedge resection by laparoscopy proceed to laparatomy due to poor accessibility because of dense adhesions caused by endometriosis. Although like other ectopic pregnancies, ovarian pregnancy can be treated with methotrexate, it is not known whether same criteria would apply. Kudo et al25 first reported the successful use of methotrexate 21

CASE REPORT to treat an ovarian pregnancy. Because of the limited literature available, unlike in tubal pregnancies, the factors predicting success with systemic methotrexate in ovarian pregnancy are not well-defined.

8. Spiegelberg O. Zur kasuistik der ovarialschwangerschaft. Arch Gynaecol. 1878;13:73-9.

Fertility after conservative surgical procedure does not appear to be affected, and ovarian wedge resection is the treatment of choice.9 Patients with ovarian pregnancy have a good prognosis for future fertility and, therefore, conservative surgical management is advocated.

10. Marcus SF, Brinsden PR. Primary ovarian pregnancy after in vitro fertilization and embryo transfer: report of seven cases. Fertil Steril. 1993;60(1):167-9.

Conclusion Ovarian pregnancy after ICSI is rare and can be easily missed unless there is a high index of suspicion. Underlying pathophysiological mechanism of Ovarian ectopic pregnancy after ICSI-ET are unclear. Indeed, gynecologists should be aware about the development of the ovarian ectopic pregnancy after ICSI-ET. Early diagnosis will give the opportunity to use conservative management for infertile patients. The therapy of early diagnosed ovarian pregnancy is surgical in the first place, and in the event that the patient desires a future pregnancy, the conservation of ovarian tissue is the clinical goal of our treatment. In our case, we preserved the ovaries and thus she could conceive later (delivered a healthy girl child). References 1. Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and infertility, 8th Edition. Philadelphia: 2011. p. 1409. 2. Shrestha A, Chawla CD, Shrestha RM. Ruptured primary ovarian pregnancy: a rare case report. Kathmandu Univ Med J (KUMJ). 2012;10(39):76-7. 3. Oliveira FG, Abdelmassih V, Costa ALE, Balmaceda JP, Abdelmassih S, Abdelmassih R. Rare association of ovarian implantation site for patients with heterotopic and with primary ectopic pregnancies after ICSI and blastocyst transfer Hum Reprod. 2001;16(10):2227-9. 4. Han M, Kim J, Kim H, Je G, Hwang T. Bilateral ovarian pregnancy after in vitro fertilization and embryo transfer in a patient with tubal factor infertility. J Assist Reprod Genet. 2004;21(5):181-3. 5. Ferland RJ, Chadwick DA, Oâ&#x20AC;&#x2DC;Brien JA, Granai CO 3rd. An ectopic pregnancy in the upper retroperitoneum following in vitro fertilization and embryo transfer. Obstet Gynecol. 1991;78(3 Pt 2):544-6.

9. Bagga R, Suri V, Verma P, Chopra S, Kalra J. Failed medical management. In ovarian pregnancy despite favourable prognostic factors â&#x20AC;&#x201C; a case report. Med Gen Med. 2006;8(2):35.

11. Spiegelberg O. Zur kasuistik der ovarialschwangerschaft. Arch Gynaecol. 1878;13:73-9. 12. Marcus SF, Brinsden PR. Analysis of the incidence and risk factors associated with ectopic pregnancy following in-vitro fertilization an embryo transfer. Hum Reprod. 1995;10(1):199-203. 13. Carter JE, Jacobson A. Reimplantation of a human embryo with subsequent ovarian pregnancy. Am J Obstet Gynecol. 1986;155(2):282-3. 14. Narvekar SA, Vijay Kumar PK, Shetty N, Gupta N, Ashwini GB, Rao KA. Unruptured ovarian pregnancy following in vitro fertilization: missed diagnosis followed by successful laparoscopic management. J Hum Repro Sci. 2008;1:3941. 15. Pope CS, Cook EK, Arny M, Novak A, Grow DR. Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes. Fertil Steril. 2004;81(1):51-8. 16. Knutzen V, Stratton CJ, Sher G, McNamee PI, Huang TT, Soto-Albors C. Mock embryo transfer in early luteal phase, the cycle before in vitro fertilization and embryo transfer: a descriptive study. Fertil Steril. 1992;57(1):156-62. 17. Geoffrey Sher. Ectopic pregnancy: causes, diagnosis and treatment. [online] Available from http://www.ivfauthority. com/2009/11/ectopicpregnancy-causes-diagnosis-and.html. [Accessed on June, 2015]. 18. Lesny P, Killick SR, Robinson J, Raven G, Maguiness SD. Junctional zone contractions and embryo transfer: is it safe to use a tenaculum? Hum Reprod. 1999;14(9):2367-70. 19. Atabekoglu CS, Berker B, Dunder I. Ovarian ectopic pregnancy after intracytoplasmic sperm injection. Eur J Obstet Gynecol Reprod Biol. 2004;112(1):104-6. 20. Comstock C1, Huston K, Lee W. The Ultrasonographic appearance of ovarian ectopic pregnancies. Obstet Gynecol. 2005;105(1):42-5. 21. Fritz MA, Speroff L. Female infertility. In Clinical Gynecologic Endocrinology and Infertility, 8th Edition. Philadelphia: Lippincott Williams and Wilkins; 2011. pp. 1137-90. 22. Patel Y, Wanyonyi SZ, Rana FS. Laparoscopic management of an ovarian ectopic pregnancy: case report. East Afr Med J. 2008;85(4):201-4. 23. Marret H, Hamamah S, Alonso AM, Pierre F. Case report and review of the literature: primary twin ovarian pregnancy. Hum Reprod. 1997;12(8):1813-5.

6. Marcus SF, Brinsden PR. Primary ovarian pregnancy after in vitro Fertilization and embryo transfer: a report of seven cases. Fertil Steril. 1993;60(1):167-9.

24. Koo YJ, Choi HJ, Im KS, Jung HJ, Kwon YS. Pregnancy outcomes after surgical treatment of ovarian pregnancy. Int J Gynaecol Obstet. 2011;114(2):97-100.

7. Steptoe PC, Edwards RG. Reimplantation of a human embryo with subsequent tubal pregnancy. Lancet. 1976; 1(7965):880-2.

25. Kudo M, Tanaka T, Fujimoto S. A successful treatment of left ovarian pregnancy with methotrexate. Nihon Sanka Fujinka Gakkai Zasshi. 1988;40(6):811-3.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

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Programed Labor and Its Effect on Labor Outcome Ruchika Garg*, Saroj Singht, Shuchi Rani Agrawal‡, Meenal Jain#

ABSTRACT Ovarian pregnancy after in vitro fertilization is rare and can be easily missed unless there is a high index of suspicion. Preservation of ovarian tissue during surgery is of utmost importance especially in subfertility patients, where the goal is to preserve the fertility. We present a case of ovarian pregnancy who had a successful intracytoplasmic sperm injection (ICSI) conception after preserving the ovary. Keywords: Hxxxxxxxxxxxxxx

rogramed labor is a protocol developed by the researchers over a period of a decade. It is based on the incorportion of the three principles of "active management of labor", synergistic application of analgesic and antispasmodic during active phase of labor and plotting of the patient's partogram to monitor events during labor, so as to detect early any dysfunctional labor and adopt timely corrective measures to optimize labor outcome. The use of alert and action lines in the management of labor is a major advancement in the obstetrical field and has helped immensely to decide how long to passively wait and watch for the progress of labor and when to interfere. Thus, it has helped to control the duration of labor and the complications associated with prolonged labor. Viewed in this context this present piece of prospective study of programed labor had been taken up to determine the influence of the programed labor protocol on the events of labor and obstetric outcome. The term active management of labor was coined by an obstetrician, O'Driscoll, to describe a process which was aimed at preventing prolonged labor (O'Driscoll et al., 1969). *Assistant Professor t Professor and Head ‡ Senior Resident # Proffessor Dept of Obstetrics and Gynaecology, SN Medical College Agra, Uttar Pradesh Address for correspondence Ruchika Garg Dept of Obstetrics and Gynaecology, SN Medical College Agra - 282 002, Uttar Pradesh E-mail: ruchikagargagra@gmail.com Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

American Congress of Obstetricians and Gynecologists (ACOG) (2003) has concluded that active management may shorten labor although it has not consistently been shown to reduce rates of cesarean delivery. Materials and Methods Place of Study

This study has been undertaken in the department of obstetrics and gynecology in SN Medical College, Agra. Aim of the Study

A study on programed labor with three principles: • Active management of labor • Synergistic application of analgesic and antispasmodic and plotting of the patient's partogram • Adopt timely corrective measures to optimize labor outcome. The aim of the study was to determine the influence of the programed labor protocol on the events of labor and obstetric outcome. Selection of Patients

• Normal primigravida/multigravida at term (confirmed by date/ultrasonography). • High-risk pregnancies are avoided. • Anesthesiologist and neonatologist should be present to evaluate the mother and baby, respectively. • Consent obtained from the patient after proper counseling about the procedure. • The patient enters the study when she is in the "active phase of labor". When cervical dilation is 23

CLINICAL STUDY more than 3 cm and effacement >50%. Show is present and cephalopelivic disproportion (CPD) has been excluded. Material

Two hundred-fifty patients who satisfied the above criteria formed the subject of our study. Method

A detailed history of each case was taken as described in the proforma with special reference to labor, i.e. duration since labor pain had started and time of rupture of membrane. A detailed personal profile regarding socioeconomic status, literacy rural/urban, booked/unbooked, referred/direct were recorded her pastobstetric history about tvpe, duration and place of delivery were inquired. History of current pregnancy, whether she had regular antenatal checkup, about immunization and type of care she had received. A thorough clinical examination of each case was carried out along with thorough obstetric examination. Analgesics and antispasmodics are given. Two milligram intravenous (IV) bolus diazepam is given at the initiation of active phase. Pentazocine 6 mg IV bolus single dose and 50-100 mg of tramadol deep intramuscular is given. Ketamine 0.25-0.5 mg/kg was given. In these doses, it does not cause respiratory depression. Antispasmodics anafortin and drotaverine were given for cervical dilatation. Early artificial rupture of the membrance was done. Partograph was maintained. Discussion In the study by Daftary and Desai (2003), out of 200 cases subjected for programed labor all patients except 2 cases of persistent occipito-posterior position were delivered within 8 hours. The mean duration of active phase of labor was 3.5 hours. Second and third stage was 32 minutes. In a study by Meena et al (2006), mean duration of 1st stage of labor was 5 hours and 45 minutes in the subjects comparet to 8 hours, 39 minutes and 3 hours, 54 minutes, respectively in the controls. The mean duration of 2nd stage was 17.46 minutes in subjects and 31 minutes in controls. The mean duration of third stage was 4.94 minutes in subject and 7.66 minutes in controls. 24

Table 1. Distribution of Cases According to Gestational Age GA in weeks

Primigravida (%)

Multigravida (%)

Total (%)

37-38

38-39

39-40

124

>40, <42

Total

149

101

250

11.6% primigravidae came in labor at 37-38 weeks of GA, 13.2% primigravidae at 38-39 a weeks of GA, 26.4% primigravida at 39-40 weeks GA and 8.4% primigravida at >40, <42 weeks of GA. Where as out of 101 cases, in multigravidae 4.4% were admitted at 37-38 weeks of GA, 80 cases at 38-39 weeks of GA, 23.2% cases at 39-40 weeks and 4.8% cases of multigravidae at >40, <42 weeks of GA.

Table 2. Rate of Cervical Dilatation Gravida

Mean rate of cervical dilation

Primigravida

1.75 cm/hr

Multigravida

2.15 cm/hr

Table 9 shows that in primigravidae cervical dilatation with oxytocin was 1.75 cm/hr and where as in multigravidae, cervical dilatation was 2.2 cm/ hr with oxytocin.

Table 3. Duration of Labor Mean duration

Primi (hr)

Multi (hr)

1st stage

4.5

2.5

2nd stage

3rd stage

2.6 min

3 min

Mean duration of labor in primi was 6.5 hrs whereas in multi it was 3.5 hrs.

In our present study, 40.42% cases were delivered within 8 hours and 47.65% cases delivered between 8 and 12 hours. Only 11.2% cases delivered after 12 hours. Daftary and associates concluded that 72% of patients had complete and satisfactory pain relief. It was also found to be safe, as all the babies had APGAR score more than 8 at the end of 5 minutes. Only 54% of the patients experienced some degree of hallucination, which were easily well controlled with diazepam, 98% of patients delivered within 5 hours. Meena et al (2006) stated that the mean time of onset of analgesia was 17 minutes. Fifty-four percentage of the subjects achieved good pain relief and 32% moderate pain relief. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CLINICAL STUDY Daftary and associate had shown that out of 200 low-risk primegravida 97% cases delivered vaginally, instrumental assisted in 6.5% of the cases and lower segment cesarean section (LSCS) rate was 3%.

Table 4. Pain Score at Initiaiton of Labor Pain score

No. of cases

Percentage

No. appreciation of pain

Meena et al (2006) stated that 98% of subjects and 94% of the controls delivered normally vaginally. Two percent of the subjects and 2% of the controls needed forceps application and 4% of the controls have ventouse extraction.

Appreciation of pain which is bearable

3.6

Presence of severe pain, desire for pain relief

16.8

Meena et al (2006) concluded that the mean Apgar score was above 7 in both the groups at 1 and 5 minutes.

Presence of severe pain, demand for pain relief

199

79.6

250

100

In our study, 79.58% of the new born babies weighted between 2.5 kg and 3.5 kg. There was only one case of neonatal death. The baby had 3 rounds of cord around the neck. Following vaginal delivery there was fetal heart sound but no respiratory movement, resuscitation was done but we were unable to revive the baby. In Daftary study group, administration of analgesic and stotispasmodic drugs are known to cause nausea, vomiting, techycardia and alteration of blood pressure. In this study, morbidity like tachycardia (82%) cases, rise of blood pressure (13% cases), fall of blood pressure (2%), nausea and vomiting (5%), pyrexia (3.5%), vaginal tear (14%), hallucination (6.5%) and anemia (12%). However, postpartum hemorrhage (PPH) and postpartum psychosis were not seen in this study. Mena et al (2006) observed tachycardia >100/minute in 4% cases, nausea (4%), vomiting (6%), diarrhea (6%), drowsiness (4%) and cervical/vaginal tears (10%).

Total

Majority cases had pain score '3', 16.8% cases with pain score '2' and 3.6% cases had bearable pain.

Table 5. Pain Relief Score with Ketamine Analgesia Pain score

No. of cases

Percentage

No relief of pain

Some relief of pain

Substantial relief of pain

Complete relief of pain

197

Analgesia not given

Total

250

It was observed that ketamine induced a frame degree of pain relief in majority of the cases.

Table 6. Mode of Delivery Mode of delivery Normal delivery

No. of cases

Percentage

218

87.2

Ventous application

3.6

Forcep application

3.2

LSCS

Total

250

100

Conclusion

Out of 250 cases undergoing programed labor in our study, 87.2% cases delivered vaginally. In 6% cases, cesarean section was done.

Active management of labor has been gaining acceptance ever since 'O' Driscoll introduced it in 1969.

• Acceleration of labor with intravenous oxytocin when ever uterine contraction was less effective.

The essence of the programed labor for active management of labor was: • Maintaining of partograms for the events of labor in each patients. So, as to intervene as and when necessary. • Judicious and synergistic administration of analgesics and antispasmodics. Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

• Most of the patients were satisfied with the protocol at the end of the deliveries. The ease of administration, the need for minimal patient monitoring with systemic analgesia has made programed labor protocol highly acceptable. The optimizing labor protocol shortens the duration of labor and the duration of 3rd stage. It improves the 25

CLINICAL STUDY Table 7. Indication for LSCS Indication

No. of cases

Foetal distress

Deep transverse arrest: failed ventouse

Persistent occipitoposterior presentation

Total

"Motherhood" a women's most cherished moment remains as natural as normal labor without any bad feelings.

In majority LSCS was done because of foetal distress in 1 stage of labor.

Table 8. Birth Weight of Babies Delivered Vaginally Weight in kg

maternal and neonatal outcome and need for obstetric interventions. Analgesia is quite effective and side effects of drugs are minimal and safe for the fetus as well.

No. of cases

Percentage

<2.5 kg

7.23

2.5-3.5 kg

187

79.58

>3.5 kg

13.19

Total

235

100

Therefore, this protocol should be tried in each and every laboring patient so that childbirth becomes an event of joy and satisfaction. Programed labor protocol seems to be a logical answer to improving our management practices.

Majority of the babies were between the birth weight 2.5 and 3.5 kg.

Table 9. Neonatal out Come Outcome

Mode of delivery VD

LSCS

Total

Live birth

234

249

Deeply asphyxiated baby

Only a single deeply asphyxiated baby, who had only heart beat at the time of delivery but could not be revived and died after 5 minutes of birth was born. This baby had three rounds of cord around the neck and did not show any sign of distress until the end of 2nd stage of labor.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT

Rapunzels Syndrome in a Six-Year-Old Child: A Case Report Shivanand Reddy KV*, Ramesh Hâ&#x20AC;

ABSTRACT Rapunzels syndrome is a rare presentation of trichobezoar with extension of hair into small bowel. Trichobezoar is a tuft of undigested hair mass commonly found in young females with psychiatric disorders.1 Rapunzels syndrome is a rare condition and occurs when gastric trichobezoar extends beyond the pylorus into the small bowel. Twenty-eight cases have been reported in English literature till 2012.2 The diagnosis of trichobezoar may be difficult due to nonspecific presentation. We present a case in a 6-year-old child who came with history of pain abdomen and features of intermittent gastric outlet obstruction. She was successfully managed by laparotomy which revealed trichobezoar with a tail measuring 48 cm in length extending till the proximal ileum. Child also had transient jejunojejunal intussusception. Keywords: Rapunzels syndrome, trichobezoar, bezoar

ezoars are collection of undigested materials that accumulate to form a mass in the gastrointestinal tract most commonly found in stomach. Various types of bezoars like trichobezoar, phytobezoar, lactobezoar, pharmacobezoar have been reported depending on their compositions. Trichobezoar is a tuft of undigested hair mass commonly found in young females with psychiatric disorders.1 Rapunzels syndrome is a rare condition and occurs when gastric trichobezoar extends beyond the pylorus into the small bowel. Twenty-eight cases have been reported in English literature till 2012.2

vomiting. Fullness and pain used to subside after vomiting. Examination revealed a palpable mass in the epigastrium. There was no definite history of trichophagia on questioning and child had no alopecia. Earlier ultrasonography done elsewhere was reported as intussusception. Computed tomography (CT) abdomen (Fig. 1) showed a hypoechoic mass lesion in the body of stomach measuring about 8*7 cm. Barium meal (Fig. 2) revealed a filling defect in the

Case Presentation A 6-years-old female child presented with pain abdomen since 1 month for which she approached a family physician and was treated as a case of worm infestation. However, the pain in the epigastric region progressively increased from past 15 days which was more after having food. Mother noticed fullness in the epigastric region after taking food from past 10 days which was followed by pain abdomen and *Postgraduate â&#x20AC; Senior Resident Dept. of General Surgery, JSSMH, Mysore Address for correspondence Dxxxxxxxxxxxxx Figure 1. xxxxxxxxxxx

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT

Figure 2. xxxxxxxxxxx

Figure 4. xxxxxxxxxxx

With these findings and repeated questioning childâ&#x20AC;&#x2122;s mother admitted that she had a habit of plucking and eating hair with frontal hair loss when she was 2 years old. Endoscopic extraction using a snare was attempted but failed. A laparotomy was performed which showed a transmural ulcer adherent to the anterior abdominal wall. Gastrotomy was done and a gastric trichobezoar of 12*5 cm which had taken the shape of the stomach was extracted along with 48 cm tail in continuity (Fig. 4). A small segment of tail which was left in the jejunum was removed by enterotomy. Postoperative course was uneventful. Child was started orally on postoperative day 3 and discharged on postoperative day 7 after psychiatric counseling. Discussion

Figure 3. xxxxxxxxxxx

lumen of stomach extending into the deuodenum with linear streaks of barium within the filling defect suggestive of a trichobezoar. Endoscopy (Fig. 3) was done to confirm the diagnosis which showed a trichobezoar with its tail extending into the pylorus. 28

Trichobezoar is a tuft of hair mass in the digestive tract which is a complication of trichotillomania (plucking of hair) and trichophagia (eating hair). Although about 1 of 2,000 children suffer from trichotillomania, trichophagia is rarely seen and a bezoar does not occur in all children with trichophagia.3 Stomach is the most common site for a trichobezoar as it is not able to exteriorize hair and other substances out of its lumen because the friction surface is not sufficient for propulsion by peristalisis. Rarely these bezoars can Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT extend beyond dueodenum upto ileocecal junction, a condition termed as rapunzels syndrome.1 It can present with the symptoms of pain abdomen, vomiting, perforation, mass per abdomen, intestinal obstruction, intussusception, pancreatitis and ulceration.1 In our case, the child presented with the symptoms after a period of 4 years from the time of ingestion of hair. The tail of the gastric trichobezoar was about 58 cm in length extending till the terminal jejunum with transient intussusception. Imaging modalities like CT and barium meal helps in establishing diagnosis. Magnetic resonance imaging (MRI) is less useful compared to a CT as the signal density is low in MRI and is confused with air.4 Endoscopy can be used as a mode of diagnosing and also as a method of management. Endoscopic removal of trichobezoar have been tried in 40 patients and only 2 were successful according to the literature.5 In case of rapunzels syndrome, endoscopic removal should not be tried as it is not possible to remove the entire length of the tail which can lead to left over segments in smallbowel. Surgery is the preferred treatment in most of the cases where a gastrotomy and the enterotomy can be performed for the complete removal of the trichobezoar along with the tail. In our case, a gastrotomy was done and the gastric trichobezoar was removed in continuity with its tail of about 48 cm and a small leftover segment was removed by a separate enterotomy. The complications of rapunzel syndrome ranges from attacks of incomplete pyloric obstruction to complete obstruction of the bowel, ulceration, perforation, pancreatitis, peritonitis and mortality.6 DeBakey and Oschner reported a surgical mortality of 10.4%.7 It is mandatory to perform a thorough exploration of all the small intestine and stomach searching for retained bezoars. Underlying psychological causes have to be

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

treated as a part of management to prevent recurrences.1 Few cases of recurrences have been reported even after successful surgery. Conclusion Trichobezoar should be considered as a differential diagnosis in a female patient presenting with nonspecific abdominal complaints. Endoscopy as a preoperative management should be done to visualize extension of trichobezoar into the small bowel. In case of rapunzels syndrome, extraction of the mass by endoscopy can be incomplete because of fragmentation so laparotomy is considered as the preferred choice of treatment modality for complete extraction of the trichobezoar along with its tail. References 1. Chana RS, Aviral, Kumar R. Gastrointestinal bezoars in children with special reference to recurrent trichobezoar. JIAPS. 2004;9:25-9. 2. Naik S, Gupta V, Naik S, Rangole A, Chaudhary AK, Jain P, Sharma AK. Rapunzel syndrome reviewed and redefined. Dig Surg. 2007;24(3):157-61. 3. Pul N, Pul M. The rapunzel syndrome (trichobezoar) causing gastric perforation in a child: a case report. Eur J Pediatr. 1996;155(1):18-9. 4. O'Sullivan MJ, McGreal G, Walsh JG, Redmond HP. Trichobezoar. J R Soc Med. 2001;94(2):68-70. 5. Gorter RR, Kneepkens CM, Mattens EC, Aronson DC, Heij HA. Management of trichobezoar: case report and literature review. Pediatr Surg Int. 2010;26(5):457-63. 6. Al Wadan AH, Al Kaff H, Al Senabani J, Al Saadi AS. 'Rapunzel syndrome' trichobezoar in a 7-year-old girl: a case report. Cases J. 2008;1(1):205. 7. De Bakey M, Oschner A. Bezoars and concretions. Surgery. 1938;4:934-63

CASE REPORT

Thyroid and Pregnancy: A Systematic Review xxxxxxxxxxxxxxxxx

ABSTRACT Pregnancy acts like a stress test for the thyroid gland and results in hypothyroidism is women who are iodine deficient or have limited thyroid reserve, and postpartum thyroiditis in previously euthyroid women with underlying Hashimotoâ&#x20AC;&#x2122;s thyroiditis. However, there is inconclusive evidence to recommend for or against the universal serum TSH screening at the 1st trimester visit of a pregnant woman and trimester specific cutoff values should be used for monitoring the thyroid function (whenever performed). Nonspecific complaints like irritability or anxiety in a postpartum lady should be investigated to rule out postpartum thyroiditis and not merely considered as maladjustment on the part of the lady. Thyroid nodules can grow in size during pregnancy but usually are well tolerated and can be operated postpartum. If deemed necessary during pregnancy, surgery should be carried out in the 2nd trimester for the same. Keywords: Pregnancy, TSH, anti-TPO antibodies, L-thyroxine

regnancy impacts the functioning of the thyroid gland profoundly and is associated with a 10-40% increase in the size of the gland (iodinereplete areas show greater increase), 50% increase in the production of T4 and T3 along with a 50% increase in the daily requirement of iodine. These physiological changes can render a pregnant, iodine-deficient, euthyroid woman in the 1st trimester, hypothyroid during the later stages of pregnancy.

Human chorionic gonadotropin (hCG), secreted by the placenta, also impacts thyroid function as it simulates thyroid stimulating hormone (TSH) activity in vivo, thereby suppressing its secretion.1,2 Evidence suggests that throughout pregnancy, the TSH values are lower than the prepregnant state, and may even be below the classical lower limit of 0.4 mIU/L.3, 4 hCG concentrations are increased to a greater extent in multiple pregnancies, therefore the downward shift is even more significant in them. Since the levels of hCG decrease as the pregnancy increases, those of TSH follow *Sxxxxxxxxxxxxxx

Address for correspondence Dxxxxxxxxxxxxx

the reverse trend. Therefore, trimester specific cut-off values of TSH should be used for diagnosing hyper- or hypothyroidism during pregnancy (and not the usual ones for nonpregnant individuals). The recommended reference ranges are: 1st trimester-0.1-2.5 mIU/L, 2nd trimester- 0.2-3.0 mIU/L and 3rd trimester- 0.3-3.0 mIU/L.5 Studies also report a significant decrease in the fT4 levels with the progression of pregnancy.3,6,7 Its measurements are complicated by the increased levels of thyroid binding globulin (TBG) and decreased levels of albumin during pregnancy, which make the immunoassays unreliable.8,9 The best method to assess fT4 during pregnancy is to measure T4 in the dialysate/ultrafiltrate of the serum samples employing online extraction/liquid chromatography or tandem mass spectrometry.5 However, if these are unavailable, the clinician can use whichever method is available, with the knowledge of its shortcomings. It must be emphasized here that serum TSH is a superior indicator of thyroid function in pregnancy.5 Primary maternal hypothyroidism is defined as the increase in serum TSH levels during pregnancy. Depending upon the fT4 levels, it is further classified as Overt (OH- fT4 levels decreased) or subclinical (SCHnormal fT4 levels). This distinction is important, as studies show a more consistent relationship between adverse maternal and fetal outcomes and OH than SCH. OH is associated with an increased risk of Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CASE REPORT premature birth, low birth weight and miscarriage. Some studies found a 22% increase in the risk of gestational hypertension10 while others have found detrimental effects on neurocognitive development of the fetus.11 SCH can also be associated with similar adverse effects but the data regarding the same are inconclusive.12 Thus, all patients found to have OH should be treated with oral L-thyroxine (other preparations are not recommended). The decision whether to treat SCH remains debatable. Both OH and SCH patients should be followed up with serum TSH levels every 4 weeks up to 16-20 weeks period of gestation and then at least once between 26 and 32 weeks. Euthyroid women (not receiving L-thyroxine) who are thyroid autoantibody positive (TAb+) also require the same monitoring during pregnancy as they have increased propensity to develop hypothyroidism during the same. No treatment is required by them for TAb+ status. Negro et al13 demonstrated a significant decrease in the number of patients with postpartum thyroid depression when treated with Selenium 200 µg/day, but the increased risk of developing type 2 diabetes mellitus in this group14 made this recommendation unacceptable. Several studies conducted in USA reported a 2-3% incidence of hypothyroidism amongst healthy, nonpregnant females of child-bearing age group.15,16 Around 0.3-0.5% of these are classified in the OH group, and the rest in the SCH category. These values are likely to higher in countries with iodine deficiency. Pregnancy is a state with increased thyroid hormone requirements. As a result, around 50-85% of previously hypothyroid women (on treatment) need to increase their dose of L-thyroxine, postconception.17,19 This adjustment should be made as soon as possible after the pregnancy is confirmed and usually an increment in dose by 25-30% is required. This can either be achieved by increasing the dosage as a whole or by taking 2 extra tablets of the previous treatment per week. They are followed up the same way as newly diagnosed OH or SCH cases during pregnancy. Following delivery, the dose of L-thyroxine should be decreased to the preconception dose and serum TSH levels checked around 6 weeks postpartum. Although untreated overt hypothyroidism is associated with adverse maternal and fetal outcomes, there are no data to suggest that adequately treated patients have Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

any increased morbidity or mortality from the same. Therefore, there is no indication for additional testing or surveillance in such patients. Hyperthyroidism can also complicate pregnancies, although its incidence is lesser than hypothyroidism. Gestational hyperthyroidism is the commonest cause accounting for 1-3% cases and is characterized by “transient hyperthyroidism, limited to the first half of pregnancy characterized by elevated fT4 or adjusted T4 and suppressed or undetectable serum TSH, in the absence of serum markers of thyroid autoimmunity”.20 It is thought to occur because of high hCG levels and may be associated with hyperemesis gravidarum, multiple gestation, hydatidiform mole or choriocarcinoma.21,22 Grave’s disease is the 2nd most common cause, accounting for 0.1-1% cases23,24 and can either be diagnosed for the 1st time during pregnancy or present as a recurrent episode. Other causes include toxic multinodular goitre, toxic adenoma and factitious thyrotoxicosis. The differentiation between gestational hyperthyroidism and Grave’s disease can be made on the basis of clinical signs of Grave’s disease like goiter and endocrine ophthalmopathy. If in doubt, the determination of TSH receptor antibody (TRAb) is indicated as it will be absent in the former and present in the latter. There is inconclusive evidence for the use of thyroid ultrasound for the same in pregnancy whereas the use of radioactive iodine uptake/scanning is contraindicated.5 The management of gestational hyperthyroidism depends upon the severity of symptoms that it produces. Hyperemesis gravidarum should be treated with fluids to prevent dehydration and antiemetics. Antithyroid drugs (ATDs) are not warranted since the serum T4 levels return to normal in 14-18 weeks period of gestation and studies found that the obstetrical outcome was not improved in cases that were treated with antithyroid drugs for the same.25 Unlike gestational hyperthyroidism, those due to Grave’s disease needs treatment with ATDs and the obstetrical and medical complications are directly related to the control of hyperthyroidism and the duration of euthyroidism during pregnancy.26-29 Poor control is associated with an increased incidence of miscarriages, pre-eclampsia, prematurity, low birth weight, intrauterine growth restriction, still birth, thyroid storm and maternal congestive heart failure.30 Propylthiouracial (PTU) is preferred for treatment in 31

CLINICAL STUDY the 1st trimester and then switched to carbimazole/ methimazole for the subsequent trimesters. This is because PTU has not been associated with teratogenic effects that have been associated with the use of Carbimazole/Methimazole, but it is associated with the risk of hepatotoxicity, which may occur any time during the treatment with PTU. Beta-blockers like propranolol are used for controlling the hypermetabolic symptoms, the dose titration according to the clinical symptoms. They can usually be safely withdrawn in 2-6 weeks as prolonged use has been associated with intrauterine growth restriction, fetal bradycardia and fetal hypoglycemia.31 All antithyroid drugs cross the placenta and therefore the aim is to maintain the fT4 values at or just above the upper limit normal values using the smallest possible dose, in order to avoid harmful effects on the foetus. The fT4 values should be monitored every 2-6 weeks. Thyroidectomies are rarely indicated (allergy/ contra-indication to ATDs, non-compliance, large dose required) and should be performed in the 2nd trimester, if needed. In all hyperthyroid cases, a determination of serum TRAb around 24-28 weeks is advised as it is helpful in detecting the pregnancies at risk of fetal hyperthyroidism. A value above three times the upper limit of normal is an indication for the close follow up of the foetus. Follow up of the foetus with serial ultrasounds can be performed in such cases. However, cordocentesis should not be performed unless fetal goiter is detected in women on ATDs, to determine whether the foetus is hyper- or hypothyroid. This is because cordocentesis is associated with both fetal morbidity and mortality.32,33 Breastfeeding is safe in mothers taking ATDs in moderated doses. Methimizole can be given in doses up to 20-30 mg/day while PTU is safe upto doses of 300 mg/day. They should be administered following the feed in divided doses. Iodine requirement is increased during pregnancy because of increased thyroid hormone production, increased renal iodine excretion and fetal iodine requirements.34 Women who had adequate iodine intake before and during pregnancy have adequate iodine stores and therefore have no difficulty in adapting to the increased demands. However, individuals with inadequate stores gradually burn them out during pregnancy and may become deficient. This may lead 32

to fetal and maternal goiter and with increased rates of miscarriage, stillbirth, perinatal and infant mortality. The cognitive function of the infant is affected37-38 as normal levels of thyroid hormone are required for the neuronal migration and myelination of the fetal brain. Children born to severely iodine deficient mothers during pregnancy exhibited cretinism, characterized by profound mental retardation, motor rigidity and deaf mutism. It is the leading cause of preventable mental retardation worldwide. Lactation is also associated with increased demands.35,36 Spot urinary iodine samples are generally used for the determination of iodine status in the general population with levels <150 ug/L considered as deficient. Therefore, women with iodine deficiency should receive iodine supplementation as it decreases the chances of the aforementioned adverse outcomes. This should be instituted early because majority of the fetal development occurs in the 1st trimester. As per the WHO, the recommended total dietary intake of iodine is 250 ug/day.39 At the same time, excessive consumption of iodine is also to be avoided for the fear of fetal hypothyroidism (Wolff-Chaikoff effect) and guidelines suggest against exceeding an intake of 500-1100 Âľg/day.5 Postpartum thyroiditis (PPT) is defined as the occurrence of thyroid dysfunction in previously euthyroid women prior to pregnancy, in the 1st postpartum year.40 It is found in about 8.1% women and this prevalence varies from one region to another.41 Classically, it is characterized by transient thyrotoxicosis followed by transient hypothyroidism, finally followed by return to euthyroid state by the end of the 1st postpartum year.42 The initial thyrotoxic phase usually occurs 3 months after the delivery and is characterized by nervousness, irritability and palpitations. These symptoms, however, most of the times are not attended to and attributed falsely to anxiety neurosis occurring especially after the birth of a female child. This phase is controlled with beta blockers like propranolol and does not require antithyroid treatment. Hypothyroid phase follows this and lasts for approximately 2-6 months. It is characterized by impaired concentration, poor memory and decreased energy and these again are falsely attributed to depression on account of maladjustment in the family after the arrival of the baby. This phase should be treated with thyroxine, which can usually be withdrawn in a year. 10-20% patients with PPT become permanently hypothyroid. Therefore, yearly Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

CLINICAL STUDY screening with serum TSH is recommended in women with a prior history of PPT. PPT is considered as an exacerbation of an underlying autoimmune thyroiditis, aggravated by the immunological rebound that follows the partial immunosuppression of pregnancy.43,44 It is associated with the presence of antithyroid antibodies in the 1st trimester, with increased titers conferring an increased likelihood of the same.45 Women suffering from other auto immune disorders like type 1 diabetes mellitus46,47 and systemic lupus erythematosus48 also have an increased risk. There is a 70% recurrence rate of PPT in subsequent pregnancies amongst individuals who recover from it.49 Spontaneous pregnancy losses and miscarriages are known to occur in around 17-31% pregnancies50 and are a significant burden to the parents both emotionally and because of its propensity to cause bleeding, infections and pain. Poorly controlled diabetes mellitus and thyroid dysfunction can result in increased risk of pregnancy losses. Some studies have shown an association between the presence of thyroid antibodies (TPO and Tg) and an increased risk of pregnancy loss,51,52 even amongst euthyroid women, while some did not agree with this relation.53 A meta-analysis was conducted which found a clear association between thyroid antibodies and spontaneous abortion but did not prove causality. Therefore, there is insufficient evidence to decide whether or not to screen all pregnant women for the presence of thyroid antibodies in the 1st trimester. This holds true even for women with a history of recurrent abortions and to the question whether or not to treat such women with L-thyroxine. Thyroid nodules and thyroid cancer can present in pregnancy posing many added challenges both to the clinician and the mother. Their prevalence was found to be roughly between 3% and 21%52,54,55 and was found to increase with increasing parity. They were found to usually increase in size as the pregnancy progressed, returning to their prepregnant state postpartum54,56 while sometimes a new nodule may develop during the course of the pregnancy. Any patient discovered to have a thyroid nodule should be asked about any positive family history for the occurrence of a benign/ malignant thyroid disease. A history of any irradiation to the head and neck region during childhood should also be sought. A thorough history about the occurrence of the nodule, its rate of growth should also Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

be sought and noted down. Ultrasound of the thyroid nodule is the investigation of choice as it helps in determining its features, thereby distinguishing benign from malignant, and also evaluates the cervical lymph nodes. Thyroid function tests should also be carried out in such patients, but they are usually normal. In addition, all nodules showing progressive increase in size should be investigated by an fine-needle aspiration cytology (FNAC) (safe in all trimesters of pregnancy). Radio-iodine uptake studies are contra-indicated in pregnancy57-59 and should never be carried out. Surgery in such patients should be deferred until postpartum in all patients with benign disease or well-differentiated malignant ones unless the nodules show rapid growth, severe compressive symptoms develop or a large primary tumour or extensive lymph node metastasis is present.5 This is because several studies conducted to find any adverse impacts of pregnancy on the prognosis of benign and well-differentiated thyroid cancer did not any association.60-66 However, if surgery is deferred, these women should undergo follow-up ultrasounds every trimester to assess for the tumour growth and any need for intervention. If required, surgery should be performed during the second trimester as it is safe and not associated with any increased fetal or maternal risk.5 To conclude, pregnancy acts like a stress test for the thyroid gland and results in hypothyroidism is women who are iodine deficient or have limited thyroid reserve, and postpartum thyroiditis in previously euthyroid women with underlying Hashimotoâ&#x20AC;&#x2122;s thyroiditis. However still, there is inconclusive evidence to recommend for or against the universal serum TSH screening at the 1st trimester visit of a pregnant woman. References 1. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18(3):404-33. 2. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, FeldtRasmussen U, Henry JF, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13(1):3-126. 3. Soldin OP, Tractenberg RE, Hollowell JG, Jonklaas J, Janicic N, Soldin SJ. Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency. Thyroid. 2004;14(12): 1084-90.

CLINICAL STUDY 4. Negro R. Significance and management of low TSH in pregnancy. In: Lazarus J, Pirags V, Butz S (Eds.). The Thyroid and Reproduction. New York: Georg Thieme Verlag; 2009. pp. 84-95. 5. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-125. 6. Kahric-Janicic N, Soldin SJ, Soldin OP, West T, Gu J, Jonklaas J. Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy. Thyroid. 2007;17(4):303-11. 7. Soldin OP, Hilakivi-Clarke L, Weiderpass E, Soldin SJ. Trimester-specific reference intervals for thyroxine and triiodothyronine in pregnancy in iodine-sufficient women using isotope dilution tandem mass spectrometry and immunoassays. Clin Chim Acta. 2004;349(1-2):181-9. 8. Roti E, Gardini E, Minelli R, Bianconi L, Flisi M. Thyroid function evaluation by different commercially available free thyroid hormone measurement kits in term pregnant women and their newborns. J Endocrinol Invest. 1991;14(1):1-9. 9. Sapin R, D’Herbomez M, Schlienger JL. Free thyroxine measured with equilibrium dialysis and nine immunoassays decreases in late pregnancy. Clin Lab. 2004;50(9-10):581-4. 10. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993;81(3):349-53.

17. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid. 2002;12(1):63-8. 18. Mandel SJ, Larsen PR, Seely EW, Brent GA. Increased need for thyroxine during pregnancy in women with primary hypothyroidism. N Engl J Med. 1990;323(2):91-6. 19. Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004;351(3):241-9. 20. Goodwin TM, Montoro M, Mestman JH. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am J Obstet Gynecol. 1992;167(3):648-52. 21. Hershman JM. Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Thyroid. 1999;9(7):653-7. 22. Grün JP, Meuris S, De Nayer P, Glinoer D. The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies. Clin Endocrinol (Oxf ). 1997;46(6):719-25. 23. Patil-Sisodia K, Mestman JH. Graves hyperthyroidism and pregnancy: a clinical update. Endocr Pract. 2010;16(1): 118-29. 24. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702-55.

11. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. 1999 Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341(8):549-55.

25. Bouillon R, Naesens M, Van Assche FA, De Keyser L, De Moor P, Renaer M, et al. Thyroid function in patients with hyperemesis gravidarum. Am J Obstet Gynecol. 1982;143(8):922-6.

12. Casey BM, Dashe JS, Wells CE, McIntire DD, Leveno KJ, Cunningham FG. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol. 2006;107 (2 Pt1):337-41.

26. Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol. 1989;160(1):63-70.

13. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92(4):1263-8. 14. Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147(4):217-23. 15. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105(2):239-45. 16. Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ, et al. Maternal thyroid deficiency

and pregnancy complications: implications for population screening. J Med Screen. 2000;7(3):127-30.

27. Millar LK, Wing DA, Leung AS, Koonings PP, Montoro MN, Mestman JH. Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. Obstet Gynecol. 1994;84(6):946-9. 28. Papendieck P, Chiesa A, Prieto L, Gruñeiro-Papendieck L. Thyroid disorders of neonates born to mothers with Graves’ disease. J Pediatr Endocrinol Metab. 2009;22(6):547-53. 29. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, Vannasaeng S, Nitiyanant W, Boonnamsiri V, et al. Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol (Oxf ). 2001;54(3):365-70. 30. Sheffield JS, Cunningham FG. Thyrotoxicosis and heart failure that complicate pregnancy. Am J Obstet Gynecol. 2004;190(1):211-7.

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CLINICAL STUDY 31. Rubin PC. Current concepts: beta-blockers in pregnancy. N Engl J Med. 1981;305(22):1323-6. 32. Porreco RP, Bloch CA. Fetal blood sampling in the management of intrauterine thyrotoxicosis. Obstet Gynecol. 1990;76(3 Pt 2):509-12. 33. Daffos F, Capella-Pavlovsky M, Forestier F. Fetal blood sampling during pregnancy with use of a needle guided by ultrasound: a study of 606 consecutive cases. Am J Obstet Gynecol. 1985;153(6):655-60. 34. Glinoer D. The importance of iodine nutrition during pregnancy. Public Health Nutr. 2007;10(12A):1542-6. 35. Azizi F, Smyth P. Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf ). 2009;70(5):803-9. 36. Andersen S, Karmisholt J, Pedersen KM, Laurberg P. Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals. Br J Nutr. 2008;99(4):813-8. 37. World Health Organization/International Council for the Control of the Iodine Deficiency Disorders/United Nations Childrenâ&#x20AC;&#x2122;s Fund (WHO/ICCIDD/UNICEF) 2007 Assessment of the iodine deficiency disorders and monitoring their elimination. World Health Organization, Geneva. 38. Vermiglio F, Lo Presti VP, Castagna MG, Violi MA, Moleti M, Finocchiaro MD, et al. Increased risk of maternal thyroid failure with pregnancy progression in an iodine deficient area with major iodine deficiency disorders. Thyroid. 1999;9(1):19-24. 39. Berghout A, Wiersinga W. Thyroid size and thyroid function during pregnancy: an analysis. Eur J Endocrinol. 1998;138(5):536-42. 40. Amino N, Mori H, Iwatani Y, Tanizawa O, Kawashima M, Tsuge I, et al. High prevalence of transient postpartum thyrotoxicosis and hypothyroidism. N Engl J Med. 1982;306(14):849-52. 41. Nicholson WK, Robinson KA, Smallridge RC, Ladenson PW, Powe NR. Prevalence of postpartum thyroid dysfunction: a quantitative review. Thyroid. 2006;16(6):573-82.

46. Gerstein HC. Incidence of postpartum thyroid dysfunction in patients with type I diabetes mellitus. Ann Intern Med. 1993;118(6):419-23. 47. Alvarez-Marfany M, Roman SH, Drexler AJ, Robertson C, Stagnaro-Green A. Long-term prospective study of postpartum thyroid dysfunction in women with insulin dependent diabetes mellitus. J Clin Endocrinol Metab. 1994;79(1):10-6. 48. Stagnaro-Green A, Akhter E, Yim C, Davies TF, Magder L, Petri M. Thyroid disease in pregnant women with systemic lupus erythematosus: increased preterm delivery. Lupus. 2011;20(7):690-9. 49. Lazarus JH, Ammari F, Oretti R, Parkes AB, Richards CJ, Harris B. Clinical aspects of recurrent postpartum thyroiditis. Br J Gen Pract. 1997;47(418):305-8. 50. Ellish NJ, Saboda K, Oâ&#x20AC;&#x2122;Connor J, Nasca PC, Stanek EJ, Boyle C. A prospective study of early pregnancy loss. Hum Reprod. 1996;11(2):406-12. 51. Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990;264(11):1422-5. 52. Glinoer D, Soto MF, Bourdoux P, Lejeune B, Delange F, Lemone M, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab. 1991;73(2):421-7. 53. Sezer K, Kamel N, Unlu C, Celik HK. Impact of first trimester and postpartum period thyroid autoantibodies on abortus incidence in Turkish pregnant women. Gynecol Endocrinol. 2009;25(6):387-91. 54. Struve CW, Haupt S, Ohlen S. Influence of frequency of previous pregnancies on the prevalence of thyroid nodules in women without clinical evidence of thyroid disease. Thyroid. 1993;3(1):7-9. 55. Kung AW, Chau MT, Lao TT, Tam SC, Low LC. The effect of pregnancy on thyroid nodule formation. J Clin Endocrinol Metab. 2002;87(3):1010-4.

43. Marqusee E, Hill JA, Mandel SJ. Thyroiditis after pregnancy loss. J Clin Endocrinol Metab. 1997;82(8):2455-7.

56. Pauwels EK, Thomson WH, Blokland JA, Schmidt ME, Bourguignon M, El-Maghraby TA, et al. Aspects of fetal thyroid dose following iodine-131 administration during early stages of pregnancy in patients suffering from benign thyroid disorders. Eur J Nucl Med. 1999;26(11):1453-7.

44. Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr Rev. 2001;22(5): 605-30.

57. Berg GE, Nystrom EH, Jacobsson L, Lindberg S, Lindstedt RG, Mattsson S, et al. Iodine treatment of hyperthyroidism in a pregnant women. J Nucl Med. 1998;39(2):357-61. 58. Zanzonico PB. Radiation dose to patients and relatives incident to 131 therapy. Thyroid. 1997;7(2):199-204.

45. Smallridge RC. Postpartum thyroid disease: a model of immunologic dysfunction. Clin Appl Immunol Rev. 2000;1:89-103.

59. Herzon FS, Morris DM, Segal MN, Rauch G, Parnell T. Coexistent thyroid cancer and pregnancy. Arch Otolaryngol Head Neck Surg. 1994;120(11):1191-3.

42. Stagnaro-Green A. Postpartum thyroiditis. Best Pract Res Clin Endocrinol Metab. 2004;18(2):303-16.

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CLINICAL STUDY 60. Moosa M, Mazzaferri EL. Outcome of differentiated thyroid cancer diagnosed in pregnant women. J Clin Endocrinol Metab. 1997;82(9):2862-6. 61. Vini L, Hyer S, Pratt B, Harmer C. Good prognosis in thyroid cancer found incidentally at surgery for thyrotoxicosis. Postgrad Med J. 1999;75(881):169-70. 62. Monroy-Lozano BE, Hurtado-Lopez LM, Zaldivar-Ramirez FR, Basurto-Kuba E. Clinical behavior of thyroid papillary cancer in pregnancy: optimal time for its treatment. Ginecol Obstet Mex. 2001;69:359-62. 63. Yasmeen S, Cress R, Romano PS, Xing G, Berger-Chen S, Danielsen B, et al. Thyroid cancer in pregnancy. Int J Gynaecol Obstet. 2005;91(1):15-20.

64. Nam KH, Yoon JH, Chang HS, Park CS. Optimal timing of surgery in well-differentiated thyroid carcinoma detected during pregnancy. J Surg Oncol. 2005;91(3): 199-203. 65. Vannucchi G, Perrino M, Rossi S, Colombo C, Vicentini L, Dazzi D, et al. Clinical and molecular features of differentiated thyroid cancer diagnosed during pregnancy. Eur J Endocrinol. 2010;162(1):145-51. 66. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167-214.

Asian Journal of Obstetrics and Gynecology Practice, Vol. 1, No. 4, 2015

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