Fertility Flash - Issue 4 by VASU

ISSUE

F e Flash

HIGHLIGHTS

Fertility Flash is an academic initiative from Corona to update, medical fraternity with the latest practice changing information in infertility management. This is a bimonthly series. Through this scientiﬁc information service to the Infertility specialists, we wish to make our contribution towards fulﬁlling the dream of motherhood.

CASE STUDY Infertility due to Endometrial Osseous Metaplasia resolved by Hysteroscopy

EVIDENCE UPDATE

CONTENTS

PREFACE

Fertility decline is perhaps the most important social change that occurred in India in recent years. Infertility, though not life threatening, can cause intense agony and trauma to the infertile couples. Beyond the complexity of the subject, gynecologists/reproductive endocrinologists are facing many challenges dealing with a wide variety of clinical fertility problems. Ironically, despite of expedited investigations for better diagnosis of infertility and accelerated drug discovery, the world is still facing the outcome of infertility. This publication provides an extensive coverage of the late breakers with a goal to improve patient care by communicating the most timely and signiﬁcant advances in basic, clinical, translational and population health research, spanning the full spectrum of fertility disorders.

Association between Live Births and Statistically Signiﬁcantly Lower Initial Serum hCG Values

hCG Priming in vitro Maturation Feasible in women with PCOS Resulting in Live Birth Rates

IMAGE OF THE MONTH DIAGNOSTIC UPDATE Investigating the Cause of Early Miscarriage: Using SNP-array Analysis and Karyotyping

7 9

CONFERENCE UPDATE Prediction of SVD in Women with Prolonged Second Stage of Labor Undergoing TOLAC: Useful to Clinicians Facing Decisions Regarding Delivery Myo-Inositol: New Treatment Option for Patients with PCOS and Infertility

Metformin Viable Alternative to Insulin for the Management of Gestational Diabetes Mellitus

MEDICO LEGAL UPDATE Medico-legal Update in Obstetrics and Gynecology: Indian Scenario

CONFERENCE CALENDER

January 2019–March 2019

TREASURE HUNT

QUIZ

F e Flash CASE STUDY Infertility due to Endometrial Osseous Metaplasia resolved by Hysteroscopy Contributed by:

Dr Jaideep Malhotra President | FOGSI-2018 (Federation of Obstetric and Gynecological Societies of India) Director | Rainbow IVF, Delhi, Agra President Elect | ISPAT (Indian Society of Prenatal Diagnosis & Therapy) President Elect | SAFOMS (South Asian Federation of Menopause Societies) (2019–21) President Elect | ISAR ( Indian Society For Assisted Reproduction) (2019) Professor | Dubrovnik International University Imm. Past President | IMS (Indian Menopause Society) (2016–2017) Past President | ASPIRE (Asia Paciﬁc initiative on Reproduction)(2014–2016) Chief of Editorial Board | SAFOMS Journal (South Asian Federation of Menopause Societies) Editor in Chief | SAFOG Journal (South Asian Federation of Obstetrics & Gynecologists) Past Vice Chairperson | ICOG (Indian College of Obstetricians & Gynecologists) Member | FIGO Committee of Reproductive Medicine Member | FIGO Working Group on RDEH (Reproductive & Developmental Environmental Health)

Case Presentation Mrs. R. S. a 33 year-old female, presented to the clinical facility with complaint of primary infertility since last 13 years.

Medical History ! The patient had regular menstrual cycles every 28 to 30 days with menstrual ﬂow less than average using 1–2 pads/day.

! She was a known case of hypothyroidism since past 6 years and was taking tab Eltroxine 50 mcg once daily for the same.

! Upon further evaluation, Mrs. R. S. gave a history of second trimester evacuation done by surgical method 14 years back.

! According to couple, she had undergone a HSG ﬁve years back which showed irregular uterine cavity and restricted spill in tubes but the ﬁlms had been misplaced.

! There was no signiﬁcant history of her partner and his semen parameters were well within normal limits. 1

F e Flash

Radiological Investigations

Figure 1: Transvaginal ultrasonography of the patient showing bony calciďŹ cations in the endometrial cavity.

The baseline scanning revealed echogenic focii in endometrial cavity, suggestive of bony calciďŹ cation. The endometrial lining was thin and the rest of myometrium was normal. Bilateral adnexa and ovaries were normal.

Hysteroscopic Procedure Diagnostic and operative hysteroscopy was performed which showed stenosis in cervical OS for which dilation was carried out. The uterus wall showed 3 bony pieces inside which were removed using hysteroscopic grasper. The rest of the endometrial cavity and endometrium appeared normal and bilateral ostia were visualized. Figure 2: Hysteroscopy observations(a) presence of bony material in the endometrial cavity, (b) removal of bony pieces, (c) cleared endometrial cavity, (d) Bony pieces

Histopathological Outcomes Histopathology of the endometrial material showed osseous metaplasia.

Gynecological Follow-up The patient was advised to report in the follicular phase of next cycle to plan for endometrial evaluation. However 2

F e Flash

she reported with 6 week amenorrhoea in the next visit. On transvaginal sonography, early pregnancy with good cardiac activity was conﬁrmed.

Discussion Osseous Metaplasia is a rare clinical entity often leading to infertility. It is characterised by abnormal bone formation in the uterine endometrium. In most of the cases, the osseous change is preceded by single or recurrent 1,2

abortions. Two theories have been proposed to explain the phenomenon of bone formation in the endometrial cavity. According to the ﬁrst, embryonic bones keep developing after a previous abortion leading to osseous metaplasia. The second hypothesis states that osseous metaplasia arises from activation of multipotent stromal cells of the endometrium into osteoblastic cells that mature to produce bone.1–3 The diagnostic modalities used for the initial detection of the presence of endometrial bone or osseous materials may include Ultrasound, D&C, Radiography, Hysterosalpingogram or Hysteroscopy.3 Once detected, evacuation of bony spicules is carried out using hysteroscopic based excision. Hysteroscopy is considered as the safest approach for removal of bony pieces as it conﬁrms the complete removal under direct visualization.2,3 Infertility in women due to osseous metaplasia is attributed to the probable role of bony pieces acting as intrauterine device by preventing blastocyst implantation.2 However, in such cases, infertility has shown good prognosis after resection. Patients regain fertility and have positive pregnancy outcomes after successful and complete removal of the bony fragments.1,2

Practice Pearls ! ! ! ! !

Endometrial Osseous metaplasia is a rare, asymptomatic cause of infertility. It is recognized by the presence of bony fragments in the uterine cavity. This condition is often followed by a previous history of abortion. Hysteroscopic or ultrasonographic detection of the bony materials aids in diagnosis. Complete hysteroscopic evacuation of bony fragments embedded in the myometrium helps to regain the fertility.

References 1. Garg D, Bekker G, Akselrod F, Narasimhulu DM. Endometrial osseous metaplasia: an unusual cause of infertility. BMJ Case Reports. 2015; 2015:bcr2015209523. 2. Madaan M, Suman S, Sharma R, Kapoor N, Garg P, Raj SS. Osseous metaplasia of the endometrium and successful hysteroscopic resection: a report of two cases and a review of the literature. Asian Journal of Endoscopic Surgery. 2015 Feb; 8(1):63–66. 3. Khan SN, Modi M, Hoyos LR, Imudia AN, Awonuga AO. Bone in The Endometrium: A Review. International Journal of Fertility & Sterility. 2016; 10(2):154–161.

F e Flash

Older age, Higher FSH values and iNOA status Associated with PreDM Status A study was conducted to assess the prevalence and the risk associated with prediabetes (PreDM) in primary infertile men. A total of 744 infertile men were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones were measured in all infertile men enrolled in the study. Based on 2010 World Health Organization (WHO) reference criterion, serum analysis was done. According to the clinical criteria detailed by the American Diabetes Association (Diabetes Care 2014; 37 (Suppl. 1): S81), preDM was defined. The association between PreDM status, hormonal milieu and seminal parameters was tested using the descriptive statistics and logistic regression analyses. Using the area under the curve, the predictive accuracy of all variables was evaluated. Clinical net benefit was estimated by decision curve analysis (DCA). Results from the study reported that of the 744 men, 15.4% of the men were diagnosed with PreDM. Men with PreDM (+PreDM) were older, had higher CCI scores, lower total testosterone and sex hormone-binding globulin but higher follicle-stimulating hormone (FSH) and 17boestradiol values compared to those without PreDM (-PreDM) (all P£0.04). In +PreDM men, higher sperm DNA fragmentation index (DFI; P=0.014) and idiopathic non-obstructive azoospermia (iNOA; P<0.001) were found. As confirmed by multivariable logistic regres-

Figure 1: Decision curve analysis assessing net beneﬁt for prediction of PreDM status. The dashed line represents the net beneﬁt of using the proposed clinical model. The grey line represents the "screen-all" strategy. The black line represents the "screen-none" strategy.

ion analysis, FSH and iNOA (all P £ 0.04) were 0.10

signiﬁcantly associated with +PreDM status at older discriminating men at higher risk of a +PreDM status. The MVA model predicting men with +PreDM showed a good predictive accuracy (AUC 0.72; 95% CI

Net benefit

age. DCA demonstrated a clinical net beneﬁt in 0.05

0.66–0.81). At decision curve analysis (Fig. 1), model showed a higher net beneﬁt when applied to discriminate men at higher risk of having a +PreDM status who would need a further diagnostic evaluation.

-0.05 5.0

7.5 10.0 12.5 15.0 17.5 Threshold probability in %

20.0

Table depicts univariable (UVA) and multivariable 4

F e Flash

(MVA) logistic regression models testing the associations between clinical variables (age, BMI, CCI score, FSH, testicular volume, and iNOA) and +PreDM. Logistic regression models predicting PreDM in the whole cohort. +PreDM UVA model OR (95% CI); P

MVA model or (95% CI); P

Age

1.08 (1.05–1.11; <0.001

1.01 (1.04–1.12); 0.001

BMI

1.06 (1.01–1.12); 0.045

1.08 (0.99–1.16); 0.06

CCI

1.45 (0.97–2.16); 0.06

1.13 (0.64–1.93); 0.70

FSH

1.04 (1.02–1.06); <0.001

1.03 (1.01–1.05); 0.028

0.99 (0.95–1.03); 0.64

1.03 (0.98–1.08); 0.20

3.38 (2.14–5.32); <0.001

1.91 (1.02–3.56); 0.04

Testicular volume iNOA

Researchers of the study concluded about 15% of primary infertile men had criteria suggestive of undiagnosed PreDM. PreDM status was associated with a greater risk of hypogonadism, higher DFI values and iNOA status. To recognise men with PreDM, age, FSH values and iNOA status could be considered as useful parameters. These parameters help to implement early preventive interventions in those men at risk of the consequences from poor glycaemic control. Source: Boeri L, Capogrosso P, Ventimiglia E, et al. Undiagnosed prediabetes is highly prevalent in primary infertile men—Results from a cross-sectional study. BJU Int. 2018 Oct 16. doi: 10.1111/bju.14558.

F e Flash EVIDENCE UPDATE Association between Live Births and Statistically Signiﬁcantly Lower Initial Serum hCG Values

Women undergoing fresh vs. frozen in vitro fertilization cycles with single-day three or ﬁve

Figure 2: The mean 2-day percentage of increase in hCG according to BMI. Percent rise in hCG in 2 days 0

n=492

18.5–24.9

25–29.9

n=180

30–34.9

n=63

35–39.9

n=39

40+

n=32

n=25 n=492

BMI (kg/m2)

18.5–24.9 25–29.9

n=180 n=63

30–34.9 35–39.9 40+

n=39 n=32

embryo transfers resulting in singleton live births (³24 weeks' gestational age) from 2008 to 2015 were

Initial hCG (mIU/mL) 50 100 150 200 250 300 350 400 450

<18.5

p-value test for trend: 0.18

Class I obesity, BMI 30–34.9 kg/m ; Class II obesity: 35–39.9 kg/m ; 2 Class III obesity: 40 kg/m .

Figure 1: Mean initial hCG according to BMI. hCG was measured 16 days after oocyte retrieval or the equivalent in frozen ET cycles.

80 100 120 140 160 180 n=25

<18.5

BMI (kg/m2)

Measurement of serum human chorionic gonadotropin (HCG) concentration is a standard method to detect pregnancies at early stages. Obesity is a worldwide epidemic with 650 million adults being obese with serious associated comorbidities according to the World Health Organization. Several studies have shown that obesity is associated with lower live birth rates after IVF. The performance of this vital serum hormone in women with an elevated body mass index (BMI) is unknown. The present retrospective cohort study was conducted to assess the eﬀect of the BMI and, more speciﬁcally, obesity class on hCG levels and trends in women conceiving singletons after single ETs.

p-value test for trend: <0.0001

Class I obesity, BMI 30 to 34.9 kg/m ; Class II obesity, BMI 35 to 39.9 kg/m ; 2 Class III obesity, BMI 40 kg/m .

analyzed. Using multivariable linear and logistic regression, the initial hCG (mIU/mL, 16 days after oocyte retrieval) and 2-day percentage of hCG increase among BMI categories were compared. Results from the study reported that the initial serum hCG values correlated inversely with the BMI (P<0.0001, test for trend) (see Fig. 1). The mean initial hCG values were signiﬁcantly lower in the patients with obesity compared with patients who were non-obese receiving single embryos and delivering singletons. Low initial hCG values (100 mIU/mL) were statistically signiﬁcantly more common in the patients with obesity than in the patients who were non-obese (9.7% vs. 2.7%, respectively. Across increasing BMI classes, from

F e Flash

1.4% of normal weight patients to 15.6% of those with a BMI ³40 kg/m (P=0.001, test for trend), low initial hCG 2

values (<100 mIU/mL) were significantly more common. The mean 2-day hCG increases were similar and normal (³53%) across the BMI groups. The differences in the mean 2-day hCG increase were not statistically significant when further analyzed across BMI categories (underweight through obesity class III; P-value test for trend, P=0.18; see Fig. 2). Researchers of the study opined that patients who achieved a singleton live birth, the patients with a greater BMI had a lower mean initial serum hCG level in a dose-dependent fashion when compared with patients who were non-obese. The proportion of patients with low initial serum hCG levels was also greater among the patients who were obese, with a statistically significant difference.

The rate of hCG increase remains t he mainstay of monito ring ver y early pregnanc ies after in v itro fertilizatio n.

Source: Brady PC, Farland LV, Ginsburg ES, et al. Serum human chorionic gonadotropin among women with and without obesity after single embryo transfers. J Clin Endocrinol Metab. 2018;103(11):4209–4215.

Image of the month

Cornual twin pregnancy following IVF/ICSI treatment Source: Errázuriz J, Racca A, Schutyser V, et al. Cornual twin pregnancy following IVF/ICSI treatment. Ultrasound Obstet Gynecol. 2018;52(2):287–288.

F e Flash hCG Priming in vitro Maturation Feasible in women with PCOS Resulting in Live Birth Rates Women with polycystic ovary syndrome (PCOS) with high risk of ovarian hyperstimulation, in vitro maturation (IVM) has some advantages (lower cost and absence of ovarian hyperstimulation syndrome) over conventional in vitro fertilization (IVF). The present retrospective study analyzed the live birth rate in PCOS women undergoing human chorionic gonadotropin (hCG)-priming IVM. A total of 921 women with PCOS aged 18–42 years undergoing IVM with hCG priming were enrolled in the study. Researchers reported the live birth rate after the ﬁrst embryo transfer and cumulative live birth rate from embryos obtained in the IVM cycle. The factors predicting number of oocytes and live birth was analyzed using logistic regression model. Baseline characteristics of women enrolled in the study included (age 28.9±3.5 years, body mass index 21.8±3.1 kg/m2, infertility duration 3.7±2.6 years, 81% primary infertility, 88% ﬁrst IVF attempt, 94% ovulation induction failure).

Cumulative live birth rate (%)

Results from the study reported that the live birth rate after the ﬁrst IVM cycle ET was 31.7% (32.0% after fresh ET and 28.0% after frozen ET). The clinical pregnancy rate was higher (43.5%) but 10.3% of all pregnancies ended with miscarriage. The cumulative Figure 1: Cumulative live birth rate over 12 months after one IVM cycle. live birth rate was 33.7% (see Figure 1). The median time to achieve live birth 50 was 8.7 months. Factors signiﬁcantly correlated with the number of oocytes 40 on multi-variate analysis were BMI, 30 anti-Müllerian hormone (AMH) level, lutei-nizing hormone (LH) level, number 20 of previous IVF attempts, and ovulation 10 induction failure as the indication for IVM. When BMI, AMH and the number 0 of previous IVF attempts were higher, 0 1 2 3 4 5 6 7 8 9 10 11 12 13 the number of oocytes retrieved was Time since started IVM treatment (months) higher (p<0.001, p<0.001 and p=0.006, Number woman at risk respectively). Conversely, as LH increAll 873 873 873 873 873 873 870 854 830 634 597 583 579 579 ased the number of oocytes decreased. 0

Based on the key ﬁndings obtained from the study, researchers of the study opined that acceptable live birth rates can be achieved in women with PCOS after IVM with hCG priming. The live birth rate after IVM in women with PCOS was acceptable and similar to that after IVF.

Source: Ho VNA, Pham TD, Le AH, et al. Live birth rate after human chorionic gonadotropin priming in vitro maturation in women with polycystic ovary syndrome. J Ovarian Res. 2018;11(1):70.

F e Flash DIAGNOSTIC UPDATE Investigating the Cause of Early Miscarriage: Using SNP-array Analysis and Karyotyping Chromosome abnormality is the main causes of early miscarriage, and aneuploidies are the most common type of chromosomal abnormalities. Application of SNP array and karyotyping in early miscarriage can provide more genetic information about miscarriage, providing risk assessment to guide the next pregnancy. This was conﬁrmed in a study conducted to assess the cause of miscarriage, providing risk assessment to guide the next pregnancy. A total of 484 products of conception (POC) samples were analyzed by single nucleotide polymorphism (SNP) array, and peripheral blood samples of couples

were collected for karyotyping or ﬂuorescence in situ hybridization (FISH) analysis. Using SNP array, fresh POC samples were successfully analyzed. Results from the study reported that the rate of clinically signiﬁcant chromosomal abnormalities were 58.3% (274/468), in which rates of aneuploidy, polyploidy, partial aneuploidy, uniparental isodisomy (isoUPD), and pathogenic microdeletion/ microduplication were 43.4% (203/468), 8.8% (41/468), 3.6% (17/468), 1.9% (9/48), and 0.9% (4/468), respectively (see Fig. 1). As shown in Figure 2, most of the single aneuploidies (194 cases) were trisomies (150 cases),

Figure 1: Incidence and spectrum of various chromosome abnormalities in POC specimens. Single aneuploidy 194 (41.5%) Aneuploidy 203 (43.4%)

Double aneuploidy 6 (1.3%) Complex mosaic 3 (0.6%)

Normal results 178 (38.0%)

Abnormal results 274 (58.5%)

Triploidy 31 (6.6%)

Polyploidy 41 (8.8%)

Tetraploidy 4 (0.9%)

Total 468 cases Mosaic 6 (1.3%)

VOUS 14 (3.0%)

Benigh CNV 2 (0.4%)

Pathogenic CNV 21 (4.5%)

Partial aneuploidy 17 (3.6%) Pathogenic microdeletions/ microduplications 4 (0.9%)

UPD 9 (1.9%) isoUPD: Uniparental isodisomy, VOUS: Variants of unknown signiﬁcance

F e Flash

and the rest were monosomies (44 cases). Single trisomies were detected in all the chromosomes, except chromosomes 1, 11, 12, and 19. As shown in Figure 3, the incidences of total chromosomal abnormalities and aneuploidy abnormalities in POC specimens signiﬁcantly increased with maternal age for patients older than 35 years old. The percentage of embryonic chromosomal abnormalities signiﬁcantly increased with maternal age of patients older than 35 years old. G-banding detected 12 major chromosomal rearrangements including nine reciprocal translocations, two Robertsonian translocations, and one superfemale among 468 couples. Figure 2: Cases of each chromosomal single aneuploidy. Frequency of trisomy or monosomy 0 5 10 15 20 25 30 35 40 45 50

Figure 3: (A) The relationship between the incidences of various chromosomal abnormalities in POC specimens and maternal age; (B) The relationship between the incidence of total chromosomal abnormalities in POC specimens and maternal age.

3 4 5

Monosomy

Trisomy

7 8

The incidence of each of chromosomal abnormalities (%)

Chromosome

80 70 60 50 40 30 20 10 0

£25 yrs

£30 yrs

£35 yrs

£40 yrs

>40 yrs

Aneuploidy

39.8

38.8

39.6

68.6

71.4

Ployploidy

8.4

9.4

11.5

3.9

pCNV

4.8

4.9

6.3

UPD

1.2

3.1

1.0

72.5

71.4

£40 yrs

>40 yrs

14 15 16 17 18 19 20 21 22 X

80 70 60 50 40 30 20 10 0

54.2

56.3

58.3

£25 yrs

£30 yrs

£35 yrs

Source: Qu S, Wang L, Cai A, et al. Exploring the cause of early miscarriage with SNP-array analysis and karyotyping. J Matern Fetal Neonatal Med. 2019;32(1):1–10.

F e Flash CONFERENCE UPDATE Prediction of SVD in Women with Prolonged Second Stage of Labor Undergoing TOLAC: Useful to Clinicians Facing Decisions Regarding Delivery The present study was conducted to develop a prediction model for spontaneous vaginal delivery (SVD) in women with prolonged second stage (PSS) of labor undergoing a trial of labor after cesarean (TOLAC). A total of 364 women who met inclusion criteria term, singleton gestation, TOLAC, no prior vaginal delivery, who reached 10 cm cervical dilation were enrolled in the study. Women with normal second stage were compared with women with PSS (≥3 hours with epidural or ≥2 hours without epidural). The independent association of PSS with outcomes was examined using univariate analysis and multivariable logistic regression.

Figure 1: Incidence of SVD in lowest and highest risk quintiles.

Incidence (%)

42.5

Using the regression model, simple risk score was created to calculate maximum likelihood estimates of probabilities for each subject. The association of probability quintile with incidence of SVD was examined. Of 364 women with PSS with epidural, SVD occurred in 96 cases (26.4%). Positive association between SVD and birth weight, insurance, indication for previous cesarean and male sex was found by conducting univariate analyses. On the other hand, the multivariate model predicting SVD, showed no independent predictors. The simple risk score was calculated. The incidence of SVD in lowest and highest risk quintile is depicted in Figure 1. Based on the prediction model, risk quintile was signiﬁcantly associated with SVD (p=0.006).

13.9

0 Lowest risk quintile

Highest risk quintile

Resea rcher s of th opine e stud d tha y t pred mode iction l for S VD in with s wome inglet n under on ge going statio n TOLA and e C with pidur PSS al ma to clin y be u icians s eful facing regar decisi ding ons delive r y.

Source: Alexis G, Richard A, Charles M, et al. Prediction of Spontaneous vaginal delivery in women with prolonged second stage of labor undergoing TOLAC [11A]. Obstetrics Gynecol. 2018;131:p11S–12S.

F e Flash

Myo-Inositol: New Treatment Option for Patients with PCOS and Infertility Polycystic ovary syndrome (PCOS) plays a vital role in failure of in vitro fertilization (IVF) and in general, PCOS patients suﬀer from poor quality oocytes. In patients with PCOS, use of ×2000 mg myo- inositol+2×200 mg folic acid per day improves symptoms and fertility. Besides, it is safe and promising tool in PCOS patients.

Levels (ng/mL)

An open, prospective, non-blinded, non-comparative observational study was conducted to assess the eﬀectiveness of myo-inositol and folic acid combination in patients with PCOS and infertility. A total of 3602 infertile women used myo-inositol and folic acid between 2 and 3 months in a dosage of 2×2000 mg myoinositol+2× 200 mg folic acid per day. In addition, hormonal Figure 1: Change in testosterone and values for testosterone, free testosterone and progesterone progesterone levels after treatment. were analyzed before and after 12 weeks of treatment in subgroup of 32 patients. The mean time of use was 10.2 weeks. Student’s t-test was performed for statisticaly analyses. 96.6 100

Testosterone levels

Progesterone levels

60 43.3 40

Results from the study reported that 70% of the women had a restored ovulation, and 545 pregnancies were observed. Use of myo-inositol and folic acid resulted in 15.1% of pregnancy rate. Concomitant medication with Clomiphene or Dexamethasone was used in 19 cases. One twin pregnancy was documented. Testosterone and progesterone levels signiﬁcantly changed after 12 weeks of treatment (see Fig. 1). No relevant side eﬀects were present among the patients.

Researchers of the study concluded that myo-inositol has proven to be a new treatment option for patients with 2.1 0 PCOS and infertility. TreatBefore After ment was safe and well treatment treatment Myotolerated with similar pregInosit ol t in wo nancy rates equivalent or men w herapy ith PC even superior range than those reported using metformin as an insulin result OS s i n b sensitizer. ette fer 20

12.3

r tilizat ion ra and a tes clear trend bette to a r emb r yo q uality .

Source: Regidor P. Myo-Inositol as a safe and alternative approach in the treatment of infertile PCOS women. 2018, Abstract no FCS472.

F e Flash

Metformin Viable Alternative to Insulin for the Management of Gestational Diabetes Mellitus A study was conducted to assess the eﬀectiveness (maternal and neonatal outcomes) of Metformin in gestational diabetes mellitus (GDM) and was compared with insulin. As per DIPSI criteria (plasma glucose level of 2 hr after 75 gm of glucose ³140 mg/dl taken as GDM), all antenatal women were screened for GDM at their ﬁrst visit. If negative repeated at 24–28 weeks. Women enrolled in the study were kept on maternal nutrition therapy (MNT) for a period of 2 weeks, after which fasting and 2 hr postprandial blood sugar were done, if FBS >95 mg/dL and/or 2 hr >120 mg/dL, these women were enrolled in study and randomized into metformin and insulin group. Metformin was started from 500 mg BD and titrated and insulin was started as per the patient need. Throughout the pregnancy, all women were followed. Of 245 women included in the study, total of 81 were enrolled in the study and were randomized to receive metformin (n=40) and insulin (n=41). Baseline characteristics were similar in both groups at baseline. Only one woman required additional insulin (19I U/day) in metformin group. Maximum dose of metformin and insulin required was 3 g/day and 45 IU/day respectively. Results from the study reported less maternal hypoglycemia and weight gain in metformin group as compared to insulin group (see Fig. 1). Fetal macrosomia was noted more in metformin group (10% vs 0, p=0.038). In both the groups, the neonatal outcome and mode of delivery were comparable. Researchers of the study concluded that metformin is comparable to insulin for glycemic control in women with Gestational Diabetes Mellitus with less maternal hypoglycemia and weight gain. It is a viable alternative to insulin in resource constrained areas in developing nations.

Figure 1: Metformin comparable to insulin for glycemic control in women with GDM.

Clinical outcome 10 15 20

5% Metformin 12.5±1.2 kg

19.5% Insulin 13.32±1.59 kg

Maternal hypoglycemia Weight gain

Source: Das V, Priyanka Y, Smriti A, et al. Metformin vs insulin for management of gestational diabetes mellitus in developing nations: RCT. 2018. Abstract no FCS086.

Answers for Trazer Hunt 1=EMBRYO; 2=PLACENTA; 3=FERTILIZATION; 4=UMBILICAL; 5=CHORIONIC; 6=AMNIOTIC; 7=ZYGOTE; 8=IMPLANTATION; 9=GESTATION; 10=BLASTOCYST; 11=MORULA; 12=CONCEPTION; 13=PRENATAL; 14=FETUS

F e Flash MEDICO LEGAL UPDATE Medico-legal Update in Obstetrics and Gynecology: Indian Scenario It is deﬁned as voluntary acceptance after full understanding, by a competent patient, of a plan for medical care after physician adequately discloses the proposed plan, its risks and beneﬁts, and alternative approaches.

Types of Consent ! ! ! ! !

Informed consent Expressed consent Implied consent Surrogate consent Advance consent

Vital Components of Informed Consent

! Mental capacity of the patient to enter into a contract (this also includes their ability to understand information given)

! Complete information to be provided by doctor ! Voluntary acceptance of the procedure by the patient or person and the speciﬁc procedure

Contents of the Consent ! ! ! ! ! ! !

A description of the recommended treatment or procedure A description of the risks and benefits – particularly exploring the risk of serious bodily disability or death A description of alternative treatments and the risks and benefits of alternatives The probable results if no treatment is undertaken The probability of success and a definition of what the doctor means by success Length and challenges of recuperation and Any other information generally provided to patients in this situation by other qualified physicians

Eligibility for Consent ! ! ! ! ! !

Age (more than 18 years, in case of minor guardian to authorize) Soundness of mind Ability to understand Remember the information given Ability to deliberate and decide the treatment choices Believes that the information applies to the said patient and speciﬁc purpose

Principles of Consent ! ! ! !

Listen to patient and respect their views about their health Discuss with patient about diagnosis, prognosis, treatment, and care involved Share with patients the information they want or need in order to make a decision for themselves Respect patient’s decision

Source: Bhute A. Informed Consent in Obstetrics and Gynecology: Indian Scenario. Int J Recent Surg Med Sci. 2017;3(1):67–71.

F e Flash CONFERENCE CALENDER 62nd All India Congress of Obstetrics & Gynaecology —AICOG 2019

ME-SFOIC-Mastery & ExcellenceSingle Focus on Ovulation Induction—Conference

Indian Society for Assisted Reproduction (ISAR) 2019

Date: Jan 8–12 and Feb 1–3, 2019; Venue: Bengaluru, Karnataka

Date: Mar 1–3, 2019; Venue: Mumbai

TRAZER HUNT 2

Across

3 4 6

5 7

The outer membrane enclosing the embryo in reptiles, birds, and mammals. In placental mammals it contributes to the development of the placenta.

The attachment of the fertilized egg or blastocyst to the wall of the uterus at the start of pregnancy, often delayed in some mammals by several months.

The process of carrying or being carried in the womb between conception and birth.

The modiﬁed blastula of a placental mammal

The action of conceiving a child or of a child being conceived.

An unborn oﬀspring of a mammal, in particular an unborn human baby more than eight weeks after conception

Below

10 11 12

An unborn or unhatched oﬀspring in the process of development.

A ﬂattened circular organ in the uterus of pregnant eutherian mammals, nourishing and maintaining the fetus through the umbilical cord.

The action or process of fertilizing an egg, female animal, or plant, involving the fusion of male and female gametes to form a zygote.

Relating to or aﬀecting the navel or umbilical cord.

It surrounds a fetus, has long been considered a protected, almost inviolable, site.

A diploid cell resulting from the fusion of two haploid gametes; a fertilized ovum.

A solid ball of cells resulting from division of a fertilized ovum, and from which a blastula is formed.

Before birth; during or relating to pregnancy.

Answers for trazer hunt on page 13

*For the use of a registered medical practitioner only