Fertilioty Update

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Fertility Update IVF: Breaking new frontiers September 2012 Vol.13 No. 1

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We realise the complexities that go hand in hand with disease management and continuously looking for ways to ensure more favourable outcomes for your patients.

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Fertility Update

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IVF: Before, During and After

1.0 Editorial

T

his edition of Fertility Update largely demonstrates the giant strides made in the field of Reproductive Medicine and strategies implemented by The Bridge Clinic to bring these to our patients. We will continue to use our newsletter as the medium of communicating new and emerging trends in Reproductive Medicine in Nigeria as well as for the communication of our service offerings to our referral doctors.

We start with a joint publication on stakeholder’s views on ethical considerations in in-vitro fertilisation (IVF) and embryo transfer which presents the reader with the deliberations of a diverse pool of stakeholders in the IVF debate and demonstrates the diversity of positions that discussions on ethics and morality typically stir up.

The reader is guided into holistic health care and its impact on the success of IVF with Dr. Ajayi’s discussion on the impact of lifestyle factors on embryo quality.

Advancements in the art and science of Reproductive Medicine and IVF are brought to the fore by Oludayo Yusuf as she introduces the reader to new trends in the practice of Embryology and the profound benefits which would arise from their implementation while Onome DibosaOsadolor discusses The Bridge Clinic’s partnership with The IVF clinics Prof. Zech, a leading IVF group in Europe, and dwells on the benefits of this partnership to our clients, our partnering doctors and the field of Reproductive Medicine in Nigeria.

Do enjoy reading our newsletter.

The Fertility Update Editorial Committee

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Fertility Update

IVF: Before, During and After

1.1 Stakeholders’ Views and Opinions on Ethical Considerations in the Practice of In-Vitro Fertilisation and embryo transfer in Nigeria

R.A. Ajayi and O. J. Dibosa-Osadolor

Abstract The aim of this study was to discuss ethical issues in invitro fertilisation (IVF) and its practice in Nigeria, to enable patients make informed decisions on treatment and drive regulation of this specialised field. A think-tank session was convened with participants drawn from different backgrounds and disciplines to deliberate on key ethical issues in IVF. 10 key issues were deliberated upon at this inaugural session and it was unanimously agreed that there are no right or wrong answers when considering the ethics and morality of a chosen course as these are principally dependent on choice and circumstances. However within the legal and socio-cultural dictates of the Nigerian society, right and wrong may be clearly determined on some issues. With the expansion of the IVF industry and technology in Nigeria, a blind eye can no longer be turned to the lack of regulation in the industry. It is absolutely important that regulatory guidelines be put in place and regulatory bodies to advise and implement these guidelines be established for the protection of patient’s rights as well as their safety.

Keywords: In-vitro fertilisation (IVF), ethical considerations, IVF controversies

Available statistics indicate that the international prevalence of infertility is about 17% with 1 in 6 women within their reproductive ages experiencing delay in conception.1,2 However studies in Nigeria have suggested that the prevalence of infertility is about

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25% with 1 in 4 women of this age bracket experiencing delays in conception.3,4,5 With a population in excess of 160 million, of which about 22% are women in the reproductive age group, it is evident that Nigeria suffers a high prevalence rate of infertility. In response to these harrowing statistics and due to the high premium placed on child bearing in Nigeria, “in vitro fertilisation and embryo transfer (IVF) clinics” are proliferating across the country in efforts to address the problem.

The provision of IVF services in Nigeria is largely driven by the private sector; however a few centres are within the public sector. This private sector dominance of the IVF field is informed by a population whose health care needs far outweigh its capacity to meet them. Due to socio-economic challenges, as evidenced by our poor health indicators, the Nigerian health system falls within the 99th centile of the World Health Organisations’ (WHO) league table of health systems6. Nigeria still grapples with issues such as high rates of malaria, childhood communicable diseases, maternal morbidity and mortality which tends to shift the focus of decision makers from less urgent issues such as infertility. The IVF field in Nigeria is further hampered by lack of regulation with no structures put in place to protect the interest of the patients seeking treatment. These dynamics have contributed to controversies which have affected the practice of IVF in Nigeria.

Since the introduction of IVF7, over 4 million children have been born globally and IVF has become accepted as the cornerstone of infertility management. As with all revolutionary changes, the practice of IVF in general has been fraught with controversies which have introduced doubts about the practice. The public have always been reassured by the presence of regulatory authorities such as the Human Fertilisation and Embryology Authority (HFEA)8 in the United Kingdom. The HFEA was set up in 1990 on the recommendations of the Warnock Committee9 to ensure regulation through the licensing of the creation of embryos outside the body for treatment and research as well as the use and storage of donated gametes and embryos. The revision of the HFEA Act in 2008 introduced the rights of single parents, unmarried partners and same-sex couples to become parents through IVF. Furthermore, it clarified the scope of legitimate embryo research activities, banned sexselection for purely social reasons and advocated for the

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welfare of the child.

The need for regulation of IVF is internationally recognised with countries having set up regulatory bodies such as the Advisory Committee on Assisted Reproductive Technology (ACART) in New Zealand (ref is needed); the National Committee on Assisted Human Reproduction in Spain (ref is needed)and the National Health and Medical Research Council (NHMRC) in Australia (ref is needed). One of such guidelines is the ethical guidelines on the use of assisted reproductive technology in clinical practice and research issued by the NHMRC10. In spite of these, the practice of IVF is still under scrutiny and is unacceptable to certain aspects of the society especially on ethical as well as moral grounds.11, 12, 13 Although IVF has been practiced in Nigeria for over 20 years14 there are still no established regulatory frameworks to guide the practice and the expansion of related technology. In response to this, The Bridge Clinic (a private IVF health facility in Lagos, Nigeria) convened a think-tank session to examine ethical issues in IVF in the Nigerian context. The objective of this session was to initiate discussion on ethical issues related to the practice of IVF in an environment where regulation is currently absent, and to make recommendations on ways to cultivate a culture of ethics relating to the provision of IVF in the country.

Ethics and Medical Ethics Ethics is the branch of philosophy which addresses questions about morality.15 It has its origins in the Greek word ethos (nature/disposition/habit) which is defined as a set of principles of morals, rules of conduct, characteristic spirit and beliefs of a community, people or system. Morals, which have their origin from the Latin root moralis (custom/habit), are concerned with goodness or badness of character or disposition and the regulation of conduct.16 Although the religious perspectives on morality are absolute with God holding the position on right and wrong, socially the subject of ethics functions in the “grey area” of relativism which argues that morality is subjective and influenced by cultural perspectives.17, 18 Medical ethics addresses moral values and judgements as they pertain to medicine. It explores

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values such as autonomy which is the patient’s rights to self-determination which includes the acceptance or refusal of treatment and balances these against the benefits to society. Beneficence and non-maleficence argue that the practitioner should always act in the interest of the patient and prescribed treatment options must not be harmful respectively. Dignity and justice provide that patients as well as practitioners have rights to their dignity and decisions on who receives treatment, and that the distribution of scarce resources should be equitable. Finally, medical ethics also addresses the areas of honesty and truthfulness which mandate that fully informed patients give consent for treatment before it is carried out on them.19, 20

Methods The Bridge Clinic is the first focussed assisted conception unit in Nigeria. Established in 1996, although full operations commenced in 1999, The Bridge Clinic has continued to provide quality fertility services in Nigeria as evidenced by the birth of over 1, 200 babies from her clinics. In recognition of the need for regulation, The Bridge Clinic implemented a quality management system according to the International Organisation for Standardisation (ISO) 9001:2000 and 9001:2008 standards respectively to guide her practices and assure the safety of her patients. Furthermore, although not licensed by them, The Bridge Clinic decided to model her standards on those of the HFEA including the establishment of an Ethics committee to ensure that decisions on patient management fall within the ethical and moral frameworks of the society. Driven by her ethos of quality and standardisation of health care, The Bridge Clinic convened a think-tank session to deliberate on ethical issues relating to the practice of IVF in Nigeria.

The concept of organising a think-tank which was small enough to encourage broad considerations and submit unanimous decisions on ethical issues in IVF, yet large enough to include all the stakeholders in the IVF market was a challenge. IVF practitioners, obstetricians and gynaecologists, psychologists/psychiatrists, family physicians, quality managers, Catholic priests, Anglican reverends, Pentecostal pastors, lawyers, sociologists, women’s advocacy coalitions, the media as an interest group as well as couples who had benefitted from IVF

Fertility Update

IVF: Before, During and After

participated in the discussions.

Health as defined by the WHO is not just the absence of disease or infirmity but the total wellbeing of an individual from the physical, mental, psycho-social, religious and cultural perspectives. To this end it was important to have the key stakeholders involved in IVF deliberate on these issues from all these perspectives.

Fifty five people were formally invited to the think-tank session and a brief was attached to the invitation letters to intimate them with the topics for consideration. The list of participants is presented in the appendix.

The discussions were preceded by a presentation which set the scene for the deliberations by introducing the subject of medical ethics and IVF. Some publicised controversies with the practice of IVF globally were presented as well as some of the positions taken by key interest groups in the debates and the role of regulatory authorities in guiding the practise of this specialised area of medicine.

The discussions which were held at the Protea hotel, Ikoyi, Lagos on June 15, 2011 lasted over 4 hours. Ten key questions, ranging from the ethics of IVF itself to the treatment of single women, were addressed (see Table I).

In each case, participants were presented with objective considerations and they were requested to generate additional issues of their own as necessary. Each question was addressed by five main participants, each speaking for a maximum of two minutes, and two other participants who were given two minutes each to either support or refute the initial positions. A lay moderator who had no specific view of the issues was engaged to guide the deliberations and to ensure that a position was reached at the end of each discussion.

Responses of participants were recorded using Dictaphones and subsequently transcribed by a facilitator who also took notes during the proceedings.

An analysis of the content of the transcripts along with the detailed recommendations forms the basis of this paper. The result of our deliberations is a collective and unanimous position, of this sample of the society, being presented in this paper.

Results Similar ethical issues were addressed simultaneously by sub-groups of participants with the objectives of

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putting forward arguments on each issue and submitting a unanimous position that was representative of perspectives of this group. Each ethical issue raised was followed up by a brief on the magnitude and peculiarities of the issue in our community. The main points to be considered are summarized in Table II.

The ethics of IVF and ICSI Religious positions on these issues differ considerably with the Catholic church taking the firm position that IVF, although humanely understandable and scientifically possible, is unethical on the following grounds: 1) babies are meant to be born within the unifying and procreative good of marriage; 2) embryos would inadvertently be destroyed during IVF procedures which would amount to abortion; and 3) adjunct procedures such as embryo cryopreservation21 impinge on the intrinsic dignity and inalienable rights of the embryo to life immediately it is formed. By contract, the position of the Anglican Church is that there is a 14 day window period following fertilisation when the human embryo cannot be considered as a person. This position reflects the opinion of the Warnock Committee which was subsequently adopted by the HFEA and on these grounds IVF is considered ethical as well as legal by the English Church and the state. Islam supports IVF as an option when all natural methods of conception have failed, as long as the laws of Sharia which prescribes for the treatment of a female partner by a certified female doctor are adhered to. However, Islam is totally against the use of donor gametes and considers it as a form of adultery. Medical professionals, on the other hand, argued from the perspectives of the rights of a mother to a child especially in a society where women are stigmatised on account of infertility and declared IVF as ethical while giving families the opportunity and satisfaction of procreation. Their focus was on the need for legislation, statutory regulations and the enforcement of compliance by IVF practitioners for the empowerment and protection of patients’ rights. However, taking on the issue of the rights of the embryo to life, a call was made for the determination of the rights and age at which the embryo should be considered a person by Nigerian law.

The ethics of gamete donation and its use without spousal/ partner’s consent

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The need for gamete donation in IVF is informed by the lack of viable eggs or sperm from the couple for fertilisation in the laboratory.22 The sensitive nature of gamete donation was recognised, but with the exception of the Islamic position earlier stated, the overwhelming conclusion was that gamete donation was ethical once it is established that the couple have no chance of achieving a pregnancy with their own gametes. With respect to gamete donation without the consent of the spouse or partner, arguably more divergent views were put forward; however, the group concluded that it was unethical and probably illegal as it impinged on the rights of the spouse or partner. However it was recognised as a “grey area” with neither right nor wrong answers especially within the context of the Nigerian society where polygamy is common and widely accepted.

The ethics of surrogacy in Nigeria On the surrogacy debate, the clerics unanimously concluded that surrogacy was unethical and adoption was preferable. They argued on the moral challenges the commissioning couple face with having to pay the surrogate for carrying their baby. Participants discussed the minefield of gamete donation as it may overlap with surrogacy, the rights of the surrogate as

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the “legal parent” of the child and the psychological as well as emotional development of the child. Although the medical practitioners agreed that the surrogacy arrangement was likely to be complex, they concluded that although surrogacy is ethical, the legal and social implications must be addressed to protect the rights of the commissioning couple, the surrogate and the child.

The legalities of the “birth mother” as the mother of the child were discussed from the UK context which clearly states that surrogacy arrangements cannot be enforced by law regardless of genetic contributions to the child8.

For these reasons surrogacy arrangements should be purely altruistic and not based on financial remuneration.

The Bridge Clinic’s position on presenting surrogacy cases to its ethics committee for decision making on a case-by-case basis was submitted as well as the thoughts, which had been suggested, on adoption of the child by the commissioning couple.

The ethics of treating couples infected with the human immunodeficiency virus (HIV) in Nigeria The Islamic position on treatment of couples with HIV is unequivocal. It is considered unethical for a couple with HIV to procreate as long as there is a risk of transmission of the infection to the child. The Catholic position on IVF as an option for infertility management was reiterated

Fertility Update

IVF: Before, During and After

but the advances made with the use of anti-retroviral drugs were cited as enabling couples infected with the HIV virus to have children naturally. Furthermore the significant improvements made in the life expectancy of couple infected with the HIV virus means that they may not die from the disease. On the contrary the medical practitioners concluded that treatment of couples with HIV was ethical as science has enabled procreation at minimum risk of transmission of infection to the child23. This is particularly true with couples when both partners are infected. Furthermore in cases were one partner is not infected with the HIV virus, other ethical considerations come into play, which need to be taken into context when educating the couples on the risk of infection of the negative partner in future.

The relationship between science and religion was aptly summed in a statement made by one participant, as follows: “medical science is a service in favour of life… we are all working together because man is matter and spirit…it is about science working to promote its own good on the person according to the will of God for man”.

Treatment for the purposes of sex-selection The unanimous submission was that sex selection for social reasons was unethical even though some cultural groups in different countries place a high premium on a particular gender. For example, in Nigeria preference is for male children14 while in the United States of America statistics suggest that 80% of families actively using sex selection techniques are trying to have female children24. The group concluded that with emancipation of women in Nigeria many of the inhibitory socio-cultural practises which prevailed have slowly given way to the more progressive rights of the girl child and the woman.

However the group concluded that sex selection for medical reasons, such as the prevention of sex-linked diseases, is ethical.

The discussions veered in the direction of treatment for the purposes of family balancing when couples who have a preponderance of one sex seek treatment to balance this uneven ratio. These options are available in the United States of America through pre-implantation genetic diagnosis and MicroSort® techniques25 but have also been challenged on ethical and moral grounds such as their potential for sexual discrimination, eugenics

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which advocates the application of science to improve the genetic composition of a population and the psychological impact on the parents and the child if the procedure produces a child of a different sex.

Treatment of unmarried couples It was unanimously submitted, that within the Nigerian context, the concept of “unmarried couples” could not be entertained rather it was preferable to view the issue as two people in a relationship seeking to have a child without providing the child with the security of a home. A major issue which was debated was who had the rights to the child in the event of a breakup of this relationship and with no conclusive agreement on this point, it was concluded that treatment of unmarried couples was not ethical in the Nigerian context.

Treatment of single women On the rights of a single woman to seek treatment, the proponents argued that in Nigeria, within the context of marriage especially polygamous marriages, the mother plays the dominant role in bringing up her children. The opponents on the other hand argued against this position submitting that the rights of a child to a family unit of father and mother was a more superior argument. Overall it was difficult to support a position that challenged the sanctity of the matrimonial union and the unanimous position was that it was unethical to treat single women.

Treatment of same-sex couples On the treatment of same sex couples, the general response was that it was unethical and unacceptable in the Nigerian context. Although the matter of choice and the respect for patients’ choices to have children regardless of their sexual orientation was proffered, this was balanced with the fact that same-sex unions are not recognised in Nigeria and people with alternative sexual preferences are socially stigmatised.

The need for both a maternal and paternal figure in a child’s life was buttressed to protect the child’s psychological as well as mental development.

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Discussion Within the limits of the number of participants as well as time allocated to the proceedings, ten key ethical issues in IVF were deliberated upon and positions reached based on the predominant submission of each group.

The unanimous conclusion of these proceedings were that, as with most ethical considerations, there are no absolute answers only points of view, which if left to individuals are to a large extent informed by personal choices and prevailing circumstances. To this end, it behoves the society to lay down practical guidelines for specialised disciplines such as IVF, to ensure that patient’s rights are protected and they receive maximum utility or satisfaction from accessing these services.

With particular reference to the specific Nigerian situation, these proceedings buttress an earlier identified absence of regulation of the health care and especially the IVF field. These findings are particularly disconcerting considering the rapid expansion of this field of medicine in Nigeria. Furthermore, prior to these proceedings, no forum of this kind has been organised to afford these issues their necessary importance. The response to these proceedings provides evidence that various interest groups, stakeholders and policy networks are interested in addressing these pertinent issues but have not had the opportunity of an organised forum to achieve this.

IVF as the cornerstone of infertility management is critical to supporting families in their desire to attain parenthood. However, if it remains unregulated, the industry will become exploitative and indeed harmful

to patients. (Please list here in one or two sentences some of the potential exploitations that can result from non-regulation of IVF) The strengths of this report are that within the time constraints which prevented more robust deliberations, to date and to our knowledge, this is the only medium which has been organised to deliberate on ethical issues in IVF within the Nigerian context with the objectives of advocating for patient’s rights to safety. This is particular important as it follows up an earlier submission to the Society for Gynaecology and Obstetrics of Nigeria (SOGON), calling for the establishment of formalised regulation of the IVF industry in Nigeria, as congruent concerns and matters surrounding both interrelated issues can be underscored. This was an inaugural session and lessons learnt from this session will drive a stakeholder summit at a later date.

In this report, there are no right or wrong answers with these ethical considerations only points of view.

Our objective was to present a position that as much as possible reflects the Nigerian societal perspective on these important issues. These discussions should provide a framework for decision making for both couples who require treatment as well as the providers of the service. Furthermore it is imperative that a legislative structure, to regulate the provision of IVF services in Nigeria, be implemented at a national level and we hope that these proceedings will form the platform to begin these discussions.

For correspondence, e-mail: bridge@om.metrong.com

The questions presented for consideration 1.

Is in-vitro fertilisation (IVF) ethical?

2.

Is intra-cytoplasmic sperm injection (ICSI) ethical?

3.

Is gamete donation ethical?

4.

Is the use of donor gametes without the spouse/ partner’s consent ethical?

5.

Is surrogacy ethical?

6. Is treatment of couples infected with the human immunodeficiency virus ( HIV) ethical?

7.

Is treatment for the purposes of sex selection ethical?

8.

Is treatment of unmarried couples ethical?

9.

Is treatment of single women ethical?

10. Is treatment of same sex couples ethical?

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Fertility Update

IVF: Before, During and After

Briefs on ethical issues considered Is IVF ethical?

This is a fundamental question of whether it is right to carry out extra-corporeal (outside the body) fertilisation in couples with infertility with the main issues here relating to the disposal of spare embryos.

Is ICSI ethical?

The issue here is that the sperms used in ICSI ordinarily cannot fertilise the eggs themselves and the argument is that we are breaking a natural barrier and are forcing the fertilisation of eggs by the abnormal sperms which could ultimately have consequences on the development of the future generation.

Is gamete donation ethical? Gamete donation brings on some important issues such as procurement of donor gametes, compensation of the donors, psychological adjustment of the children into the family, anonymity of the donor and the effect on the welfare of the child.

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I s gamete donation with the spouse partner’s consent ethical?

This is a major issue here in Nigeria because we have couples with abnormal gametes requesting for treatment with donor gametes and not wanting their partners to know. This is a common occurrence in Nigeria.

Is surrogacy ethical?

The United Kingdom’s position on this issue is that it is difficult to enforce a surrogacy arrangement as the birth mother is the legal mother of the child. The Nigerian position is worthy of discussion.

I s treatment of couples infected with the human immunodeficiency virus (HIV) ethical?

The issue with HIV infection are the life expectancy of the couple; the risks of transmission of the virus to the child and the risk of infection of the attending staff as they carry out procedures in the centre

I s treatment for the purposes of sex selection ethical?

Is it right to choose the sex of your child? We would like to discuss this within the Nigerian context where a higher premium is placed on bearing male children.

I s treatment of unmarried couples ethical?

There are some countries where the treatment of unmarried couples is unacceptable because of the belief that a child should be born into a “matrimonial union”. With globalisation and the adoption of western ideals we are starting to receive requests to treat unmarried couples in Nigeria.

I s treatment of single women ethical?

There is an increasing population of single “career” women in Nigeria today who want to have children by IVF with donor gametes.

I s treatment of same-sex couples ethical?

In the United Kingdom, for example, it is acceptable for same sex couples to use IVF technology to have children and we have had similar requests in Nigeria.

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REFERENCES 1. Guendelman, S. and Stachel, L. (2011) Infertility status

13. Klein, J. U and Sauer, M. V. (2010) Ethics in egg donation:

and infertility treatment: racial and ethnic disparities in

past, present and future. Thieme Medical Publishers. 28 (4):

Reducing racial/ ethnic disparities in reproductive and

322 – 328

perinatal outcomes. Springer 2. Gurunath, S.; Pandian, Z.; Anderson, R. A. and Bhattacharya, S. (2011) Defining infertility – a systematic review of prevalence studies. Human Reproduction Update.

July – August. 17 (4) 3. Adetoro, O. O. and Ebomoyi, E. W. (1991) “The prevalence of infertility in a rural Nigerian community”. African Journal of Medical Sciences. March; 20 (1): 23 - 7 4. Okonofua, F. E.; Harris, D. and Odebiyi, A. (1997) “The

D. (2002) Social and ethical aspects of assisted conception in Anglophone sub-Saharan Africa. Medical, Ethical and Social Aspects of Assisted Reproduction. Current practices and controversies in assisted reproduction: report of a WHO meeting (Geneva Switzerland) 15. Rist, J. M. (2002) Real ethics: reconsidering the foundations of morality. Cambridge University Press.

social meaning of infertility in Southwest Nigeria”. Health

16. Sandel, M. J. in Winston, M. and Edelbach, R. (2011)

Transition Review. 7: 205 – 220

Society, ethics and technology. Cengage Learning.

5. Sule, J. O.; Erigbali, P. and Eruom, L. (2008) “Prevalence of

17. Hocutt, M. (2000) Grounded ethics: the empirical bases

infertility in women in a south-western Nigerian community”.

of normative judgments. Transaction Books.

African Journal of Biomedical Communications Group. 11: 225 – 227 6. World Health Report 2000 Health Systems: Improving Performance. www.who.int/ 7. Steptoe, P. C. and Edwards, R. G. (1978) “Birth after the reimplantation of the human embryo”. The Lancet 312

18. Pojman, L. P. and Fieser, J. (2008) Ethics: Discovering right and wrong. 6th edn. Cengage Learning.

19. Schwartz, L.; Preece, P. E. and Hendry, R. A. (2002) Medical Ethics: a case based approach. Elsevier Health Sciences.

20. Jackson, J. C. (2006) Ethics in medicine. Polity Press.

(8085): 336

21. Donnez, J. and Kim, S. S. (2011) Principles and practice of

8. Human Fertilisation and Embryology Authority (HFEA)

fertility preservation. Cambridge university press.

Code of Practice. 8 edn. 2009

22. Klein, J. U and Sauer, M. V. (2010) Ethics in egg donation:

9. Report of the committee of inquiry into human

past, present and future. Thieme Medical Publishers. 28 (4):

fertilisation and embryology (1984) Chairperson: Dame

322 – 328

Mary Warnock DBE. Her Majesty’s Stationery Office.

23. Levine, B. A.; Nurudeen, S. K.; Gosselin, J. T. and Sauer, M.

10. National Health and Medical Research Council (2007)

V. (2011) Addressing the fertility needs of HIV-seropositive

“Ethical guidelines on the use of assisted reproductive

males. Future Virology. 6 (3) 299 – 306

technology in clinical practice and research (ART guidelines)” 11. Benagioano, G.; Mori, M.; Ford, N. and Grudzinskas, G. (2011) Early pregnancy wastage: ethical considerations.

Reproductive Biomedicine. 22 (7) 692 – 700 12. Berry, R. M. (2011) A small bioethical world? HEC Forum.

Special issue: Global bioethics: theory, policy, practice and education. 23 (1) 1 – 14

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14. Giwa-Osagie, F. O. in Vayena, E.; Rowe, P. J. and Griffin, P.

24. Bhaskar, V. (2011) Sex selection and gender balance.

American Economic Journal: Microeconomics. 3 (1): 214 – 244 25. MicroSort. Gender selection for family balancing and genetic disease prevention. www.microsort.com

Fertility Update

IVF: Before, During and After

1.2 The impact of lifestyle factors on embryo quality R.A. Ajayi

Introduction There are many factors that determine pregnancy rates in in-vitro fertilisation (IVF). One of the most important determinants is the quality of the IVF clinic in terms of the quality management systems that the clinic has deployed to ensure the generation of embryos that have implantation potential. Patient factors are also very important and issues such as the body mass index (BMI) and age of the woman at the time of egg collection are common factors for consideration. It is increasingly becoming clear that lifestyle factors also have a bearing on embryo quality and the objective of this paper is to introduce the reader to these issues. A preliminary study was carried out by the IVF centres Prof. Zech, one of our affiliate centres, where 1684 men undergoing IVF were given a questionnaire to investigate the effects of certain lifestyle factors on semen parameters in particular sperm vacoulation as defined by the MSOME criteria for semen analysis. This paper presents the results of this study.

imparting on blastocyst development. This fact is supported by its usefulness in identifying vacuoles and chromatin abnormalities which are not evaluated with the same precision as other universally accepted criteria for semen analyses such as the Tygerberg Strict criteria (see Table II).6 Other statistically significant benefits of using MSOME in IVF cycles include demonstrable improvements in implantation and pregnancy rates as well as significant reduction in miscarriage rates7,8.

A preliminary study was done on 1684 men who had undergone IVF at the centre to investigate the influence

Classification of spermatozoa Spermatozoa

Characteristics with MSOME magnification

Class I spermatozoa

Normal shaped sperm without vacuoles or with 1-2 small vacuoles <4% of the head length

Class II spermatozoa

Normal shaped sperm with ≥1 large vacuoles >4% head area

Methods Motile Sperm Organelle Morphology Examination (MSOME) was developed by Bartoov et al for real-time evaluation of sperm morphology1. MSOME is a method of semen analysis which is accomplished by achieving high magnification in excess of 6000X, which is grossly higher than magnifications used by embryologists for sperm selection for intra-cytoplasmic sperm injection typically 400X, by the use of high-powered Nomarski differential inference contrast optics2 resulting in better viewing, better sperm selection and ultimately improved pregnancy rates3,4. Conventional semen analyses investigate parameters such as semen volume, sperm concentration, motility, vitality and morphology while MSOME assessment extends itself by examining the sperm head length, width and area as well as vacuole number, vacuole area and relative vacuole area to sperm head5. Spermatozoa are subsequently classified according to the presence of nuclear vacuoles (see Table I).

MSOME as a method for sperm selection has revealed that the presence of nuclear vacuoles in human sperm adversely affects pregnancy rates with IVF by directly

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Class III spermatozoa Sperm with abnormal morphology with or without vacuoles

ygerberg-Kruger Strict criteria for analysis T of sperm morphology ruger Strict K morphology

Prognosis

≥ 15% normal forms

Normal range; good prognosis

– 14% normal 5 forms

Sub optimal range; prognosis is fair to good, however, the lower the percent normal, the lower the chance of successful fertilization

0 – 4% normal forms

Poor prognosis: will usually need IVF with intracytoplasmic sperm injection (ICSI)

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of lifestyle factors such as the age of the man, his BMI, caffeine consumption, alcohol consumption, smoking, exercise, sexual activity, frequency of ejaculation, increased stress perception and nutrition on MSOME criteria. An extensive questionnaire was administered and the data was retrospectively correlated to the semen analysis and MSOME results of each patient.

Results Effects of age There is a wealth of evidence on the changes in semen parameters as a man advances in age with most studies agreeing that parameters such as motility, vitality and normal morphology are negatively correlated with a manâ&#x20AC;&#x2122;s age while other parameters like concentration, volume and total sperm number do not decline with age.9,10,11,12,13 More recent clinical studies have been inconclusive on the exact impact of age on semen parameters14 and some have even suggested that sperm concentration and diploidy increase with advancing age in spite of a decline in semen volume and sperm vitality.15 The study revealed a significant (p<0.001) decrease in sperm quality according to the World Health Organisation (WHO) criteria with respect to sperm count and sperm motility when comparing men below the

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age of 50 (n = 1598) and men above the age of 50 (n = 85). MSOME results showed no significant differences but revealed a moderate trend towards class I sperms in younger patients.

Effects of body mass index (BMI) Body mass index has been demonstrated to affect sperm quality and total normal motile sperm volume in the ejaculate.16 Studies reveal that male BMI below 20 and above 25 is associated with a reduction in sperm quantity and quality as evidenced by a positive correlation between BMI and sperm DNA fragmentation index.17 More recent studies also confirm that parameters such as sperm concentration and motility as well the male reproductive potential are affected by paternal obesity as evidenced by decreased blastocyst development and reduced live birth rates following IVF.18,19,20 A mouse-model to determine the effect of paternal-induced obesity on sperm function, its physiology and resulting fertilisation potential revealed that obesity induced oxidative stress and sperm DNA damage resulting in decreased fertilising ability, impaired embryo development and implantation.21 The study found significant differences in semen parameters according to WHO criteria in patients with BMI below 25 and those with BMI above 25; sperm

Fertility Update

IVF: Before, During and After

motility was decreased in the group with BMI above 25 (p > 0.01). However according to the MSOME criteria there was just a trend between men with BMI less than 25 (n = 692) in comparison with those with BMI above 25 (n = 986) with class I sperms being more evident in men with a lower BMI. This confirmed the impact of BMI on sperm quality but there was no significant effect on vacoulisation rate.

Effects of caffeine Caffeine, the principal ingredient in cola drinks, coffee and in Nigeria cola nut, when consumed in high quantities i.e. in excess of 14 bottles of cola drinks (50cl bottles) or >800mg/day of caffeine may be associated with reduced sperm concentration and total sperm count.22 There is increasing evidence that environmental factors which include the daily consumption of high volumes of caffeine does negatively impact on the quality of sperms with increased sperm DNA fragmentation compared with men who do not consume caffeine.23 The results of the study showed no significant changes with MSOME criteria for sperm selection although there was still a marked tendency towards a reduced quality of sperm cells i.e. less class I sperms seen in men whose daily consumption of coffee was in excess of 3 cups. There were no significant differences on semen analysis with the WHO criteria.

Effects of alcohol Studies have extensively proven the relationship of maternal alcohol consumption and the development of abnormalities of semen quality in the male offspring of these mothers.24 However there is no conclusive evidence of an association between male alcohol consumption and semen quality.

The study did not reveal any significant changes in WHO or MSOME criteria in men who consume alcohol.

However there was a slight trend towards more class I sperm with occasionally (n = 1127) or daily alcohol (n = 164) consumption versus men who do not consume alcohol (n = 282).

Effects of smoking Smoking has been shown to negatively affect sperm production, its motility, its morphology and is associated

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with an increased risk of DNA damage with links to Cadmium as the possible causative agent for the sperm abnormalities.26,27,28 Some studies have suggested a reduced pregnancy rate associated with male smoking possibly due to pre-zygotic genetic damage.29,30,31 The study found no changes in semen parameters visĂ -vis smoking using the WHO criteria for semen analyses.

However significant changes were observed according to MSOME criteria with smokers (n = 199) and non-smokers (n = 1380) having the same amount of class I sperms (6.1%) in their ejaculate. Interestingly the study found a higher prevalence of class III sperms in the ejaculate of non-smokers.

Effects of sexual activity Statistics suggest that on average men in the United States (US) between the ages of 30 and 39 years have intercourse at least 7.1 times per month while men between the ages of 40 and 49 years have intercourse 5.7 times in a month. Other studies suggest that men and women in the US between the ages of 25 and 45 years have sexual intercourse a mean 5.7 and 6.4 times per month respectively.32 It has been suggested that there is a positive correlation between ejaculation frequency and sperm motility.

The study revealed that men who ejaculate more than four times in one month (n = 1519) had significantly more class I sperms in their ejaculate than their counterparts who ejaculate less frequently which confirms a positive correlation between frequency of ejaculation and semen parameters.

Effects of psychological stress There is some evidence of a correlation between psychological stress and declining semen quality even in male IVF patients at egg collection. However as infertility and IVF are both associated with significant levels of stress it is difficult to determine whether stress contributes to or is a consequence of infertility and IVF treatment.

Ironically, the study revealed that men with the highest levels of stress at the time of treatment (n = 431) had significantly better sperms than men who either had no stress or moderate stress levels (n = 1163). These results were seen when analysing the semen according to WHO criteria (p < 0.001) as well

15

as according to MSOME (p < 0.001). The perception of stress is consequent on several endocrine parameters such as testosterone, dehydroepiandosterone sulphate (DHEAS), cortisone, luteinizing hormone, prolactin and follicle stimulating levels.

Effects of exercise The effect of exercise on male reproductive potential depends on the duration and intensity of the physical activity and not necessarily on the regularity of exercise.

That said strenuous physical activity such as performed by highly trained athletes, the stress of exercise has been shown to inhibit gonadal function through the production of glucocorticoids and catecholamines as well as through the activation of the CRH neurons. These effects feedback to lower sperm concentration and total normal sperm count in the ejaculate.34,35 The participants in the study were men who engaged in regular, non-strenuous physical exercise and there were no significant changes on analysis of their semen with MSOME criteria or WHO criteria.

Effects of nutrition The impact of nutrition on sperm quality has been investigated extensively. Researchers have found a relationship between consumption of saturated fat and poor semen quality and studies have shown that infertile men had lower concentrations of Omega 3 fatty acids in their spermatozoa than fertile men.36 A high intake of meat and dairy products was also shown to be associated with poor semen quality, while eating fruits and vegetables apparently have a positive impact on semen quality. This beneficial impact of fruits and vegetables has been traced to their high vitamin content, especially vitamins C and E which are rich sources of antioxidants. These antioxidants, including the B-carotenes and micronutrients such as Zinc have been demonstrated to be key determinants of sperm quality and reproductive potential in a number studies. Studies have further reported the benefits of oral antioxidant therapy, of the right concentration, to the improvements of sperm quality. These beneficial effects are thought to be the result of the developing sperms being protected from oxidative stress.37,38 Self-assessment of 1006 participants in the study revealed that 98.5% perceived that the consumed

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a healthy diet with only 1.4% thinking otherwise.

66.9% of them had â&#x2030;¤1 serving of fruits or vegetables daily. Following antioxidative treatment, the study demonstrated a highly significant increase in sperm motility (p < 0.001) according to WHO criteria of semen analysis as well as a highly significant reduction in vacuolisation with grade I sperms increasing from a mean of 5% to 6.6% (p < 0.5).

Conclusion The study confirms the impact of lifestyle factors on embryo quality. A preliminary study was carried out by the IVF centres Prof. Zech where 1684 men undergoing IVF were given a questionnaire to investigate the effects of certain lifestyle factors on semen parameters in particular sperm vacoulation as defined by the MSOME criteria for semen analysis. The results of the analyses using MSOME criteria serve as a surrogate for embryo quality, a position which was corroborated

by Vanderzwalmen et al, as the quality of semen in directly correlated with the development of good quality embryos and high pregnancy rates.

The study findings revealed that lifestyle factors such as age, BMI, perceptions of stress, sexual activity and high caffeine intake not only have an effect on sperm parameters according to the WHO criteria but also on the MSOME criteria which correlates with successful outcomes of IVF treatment cycles. A combination of these factors creates a multiplier effect resulting in high levels of reactive oxygen species in the semen of male patients resulting in a reduction in their fertility potential.

The importance of lifestyle medication for couples undergoing IVF cannot be overemphasized. The study lends credibility to previous studies which have advised couples undergoing treatment to manage their weight within normal BMI limits, to limit their consumption of alcohol and caffeine and stop smoking, to eat a healthy balanced diet including fruits and vegetables and to indulge in mild to moderate exercise. This study has also contributed to new and emerging research on the role and benefits of antioxidative therapy as an adjunct to IVF treatment in men and women.

For correspondence: fertilityupdate@thebridgeclinic.com

Fertility Update

IVF: Before, During and After

REFERENCES 1. Bartoov, B.; Berkovitz, A.; Eltes, F.; Kogosowski, A.; Menezo, Y and Barak, Y. (2002) Real-time dine morphology of motile human sperm cells is associated with IVF/ICSI outcome.

Journal of Andrology. 23:1 – 8 2. Oliveira, J.B.A; Petersen, C.G.; Massaro, F.C.; Baruffi, R.L.R.; Mauri, A.L.; Silva, L.F.; Ricci, J. and Franco, J.G. (2010) Motile sperm organelle morphology examination (MSOME): intervariation study of normal sperm and sperm with large nuclear vacuoles. Reproductive Biology and Endocrinology.

8:56 3. Bartoov, B.; Berkovitz, A.; Eltes, F.; Kogosovky, A.; Yagoda, A.; Lederman, H.; Artzi, S.; Gross, M. and Barak, Y. (2003) Pregnancy rate are higher with intracytoplasmic morphologically selected sperm injection than with conventional intracytoplasmic injection. Fertility and Sterility.

80:1413 – 1419 4. Junca, A.; Cohen-Bacrie, M. and Hazout, P.A. (2004) Improvement of fertilisation and pregnancy rate after intracytoplasmic fine morphology selected sperm injection.

Fertility Sterility. 82:S173 5. Perdrix, A.; Saidi, R.; Menard, J.F.; Gruel, E.; Milazzo, J.P., Mace, B. and Rives, N. (2012) Relationship between conventional sperm parameters and motile sperm organelle morphology examination (MSOME). International Journal of Andrology. Mar 15. doi: 10.1111/j.1365-2605.2012.01249 6. Oliveira, J.B.A; Massaro, F.C.; Mauri, A.L.; Petersen, C.G.; Nicoletti, A.P.M.; Baruffi, R.L.R. and Franco, J.G. (2009) Motile sperm organelle morphology examination is stricter than Tygerberg criteria. Reproductive Biomedicine Online.

18(3):320 - 326 7. Vanderzwalmen, P.; Hiemer, A. Rubner, P.; Bach, M.; Neyer, A.; Stecher, A. et al (2008) Blastocyst development after sperm selection at high magnification is associated with size and number of vacuoles. Reproductive Biomedicine Online.

17:5617 – 5627 8. Nadalini, M.; Tarozzi, N.; Distratis, V.; Scravacelli, G. and Borini, A. (2009) Impact of intracytoplasmic morphologically selected sperm injection on assisted reproduction outcome: a review. Reproductive Biomedicine Online. 19(S3):45-55 9. Jung, A.; Schuppe, H.C. and Schill, W.B. (2002) Comparison of semen quality in older and younger men attending and andrology clinic. Andrologia. 34: 116-122 10. Eskenazi, B.; Wyrobek, A. J.; Sloter, E.; Kidd, S.A.; Moore,

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L.; Young, S. and Moore, D. (2003) The association of age and semen quality in healthy men. Human Reproduction.

18(2):447 – 454 11. Levitas, E.; Lunenfeld, E. and Weisz, N. (2007) Relationship between age and semen parameters in men with normal sperm concentration: analysis of 6022 semen samples.

Andrologia. 39:45 - 50 12. Zhu, Q.; Meads, C.; Lu, M.; Wu, J.; Zhou, W. and Gao. E. (2011) Turning point of age for semen quality: a populationbased study in Chinese men. Fertility and Sterility. 96(3):572 – 576 13. Silva, L.F; Oliveira, J.B; Petersen, C.G; Mauri, A.L; Massaro, F.C; Cavagna, M.; Baruffi, R.L and Franco, J.G (2012) The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME). Reproductive Biology and Endocrinology. 3(19):10 - 19 14. Suer, E.; Gulpinar, O. and Yaman, O. (2012) The effects of aging on fertility in men. Turkish Journal of Urology. 38(1): 40 – 43 15. Brahem, S.; Mehdi, M.; Elghazel, H. and Saad, A. (2011) The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. Journal of Assisted Reproduction and Genetics.

28(5): 425 – 432 16. Kort, H.I.; Massey, J.B.; Elsner, C.W.; Mitchell-Leef, D, Shapiro, D.B.; Witt. M.A. and Roudebush, W.E. (2006) Impact of body mass index values on sperm quantity and quality.

Journal of Andrology. 27(3): 450-452 17. Jensen, T.K.; Andersson, A.; Jorgensen, N; Andersen, A.; Carlsen, E.; Petersen, J.H. and Skakkebaek,N. (2004) Body mass index in relation to semen quality and reproductive hormones among 1558 Danish men. Fertility and Sterility.

82(4):863 - 870 18. Hammoud, A.; Wilde, N.; Gibson, M.; Parks, A.; Carrell, D.T. and Meikle, A.W. (2008) Male obesity and alteration in sperm parameters. Fertility and Sterility. 90(6): 2222 – 2225 19. Chavarro, J.E.; Toth, T.L.; Wright, D.L.; Meeker, J.D. and Hauser, R. (2010) Body mass index in relation to sperm quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic.

Fertility and Sterility. 93(7):2222 – 2231 20. Bakos, H.W.; Henshaw, R.C.; Mitchell, M. and Lane, M. (2011) Paternal body mass index is associated with

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decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertility and Sterility. 95(5):1700 – 1704 21. Bakos H.W.; Mitchell, M.; Setchell, B.P. and Lane, M. (2011) The effect of paternal diet-induced obesity on sperm function and fertilisation in a mouse model. International Journal of Andrology. 34(5):402 – 410 22. Jensen, T.K.; Swan, S.H.; Skakkebaek, N.E.; Rasmussen, S. and Jorgensen, N. (2010) Caffeine intake and semen quality in a population of 2554 Danish men. American Journal of Epidemiology. 171(8): 883 – 891 23. Giwercman, A. (2011) Sperm Chromatin and environmental factors in Zini, A. and Agarwal, A. (2011) Sperm Chromatin: Biological and clinical applications in male infertility and assisted reproduction. Springer. Pages 361 – 374.

24. Ramlau-Hansen, C.H.; Toft, G.; Jensen, M.S.; StrandbergLarsen, K.; Hansen, M.L. and Olsen, J. (2010) Is maternal alcohol consumption during pregnancy a cause of decreased semen quality in the male offspring? Human Reproduction.

25 (Issue suppl.1): i71 – i72 25. Ramlau-Hansen, C.H.; Toft, G.; Jensen, M.S.; StrandbergLarsen, K.; Hansen, M.L. and Olsen, J. (2010) Maternal alcohol consumption during pregnancy and semen quality in the male offspring: two decades of follow up. Human Reproduction. 25(9) 2340 – 2345 26. Trummer, H.; Habermann, H.; Hass, J. and Pummer, K. (2002) The impact of cigarette smoking on human semen parameters and hormones. Human Reproduction.

17(6):1554 - 1559 27. Vine, M. F.; Tse, C.K.; Hu, P. and Truong, K.Y. (1996) Cigarette smoking and sperm quality. Fertility and Sterility.

65(4): 835 – 842 28. M.F. El Shal, M.F.; El Sayed, I.H.; El Saied, M.A.; El Masry, S.A. and Kumosani, T.A. (2009) Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities in idiopathic infertile subjects: association with cigarette smoking. Clinical Biochemistry. 42(7/8): 589 - 594 29. Soares, S. R. and Melo, M. A. (2008) Cigarette smoking and reproductive function. Current Opinion in Obstetrics and Gynaecology. 20(3): 281 – 291 30. Zitzmann, M.; Rolf, C.; Nordhoff, V.; Schrader, G.; Rickert Fohring, M.; Gassner, P. et al. (2003) Male smokers have decreased success rate for in-vitro fertilisation and

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intracytoplasmic sperm injection. Fertility and Sterility. 79(3): 1550 - 1554 31. Waylen, A.L.; Metwally, M.; Jones, G.L.; Wilkinson, A.J. and Ledger, W.L. (2009) Effects of cigarette smoking upon clinical outcomes of assisted conception: a meta-analysis. Human Reproduction Update. 15(1): 31 – 44 32. Eisenberg, M.L.; Shindel, A.W.; Smith, J.F.; Breyer, B.N. and Lipshultz, L.I. (2010) Socioeconomic, anthropomorphic and demographic predictors of adult sexual activityin the United States: data from the national survey of family growth. The Journal of Sexual Medicine. 7(1): 50 – 58 33. Clarke, R.N.; Klock, S.C.; Geoghegan, A. and Travassos, D.E. (1999) Relationship between psychological stress and semen quality among in-vitro fertilisation patients. Human Reproduction. 14(3): 753 – 758 34. Safarinejad, M.R.; Azma, K. and Kolahi, A.A. (2009) The effects of intensive, long-term treadmill running on reproductive hormones, hypothalamus-pituitary-testis axis, and semen quality: a randomised controlled study. Journal of Endocrinology. 200(3): 259 - 271 35. Wise, L. A.; Cramer, D.W.; Hornstein, M.D.; Ashby, R.K. and Missmer, S.A. (2011) Physical activity and semen quality among men attending an infertility clinic. Fertility and Sterility. 95(3): 1025 – 1030 36. Attaman, J.A.; Toth, T.L.; Furtado, J.; Campos, H.; Hauser, R. and Chavarro, J.E. (2012) Dietary fat and semen quality among men attending a fertility clinic. Human Reproduction.

27(5): 1466 - 1474 37. Vujkovic, M.; de Vries, J.H.; Dohle, G.R.; Bonsel, G.H.; Lindemans, J.; Macklon, N.S.; van der Spek, P.J.; Steegers, E.A.P. and Steegers-Theunissen, R.P.M. (2009) Association between dietary patterns and semen quality in men undergoing IVF/ICSI treatment. Human Reproduction. 24(6): 1304 – 1312 38. Shamsi, M.B.; Venkatesh, S.; Tanwar, M.; Talwar, P.; Sharma, R.K.; Dhawan, A.; Kumar, R.; Gupta, N.P.; Malhotra, N.; Singh, N.; Mittal, S. and Dada, R. (2009) DNA integrity and semen quality in men with low seminal antioxidant levels. Mutation Research/ Fundamental and Molecular Mechanisms of Mutagenesis. 665(1-2):29 – 36 39. Mendiola, J.; Torres-Cantero, A.M.; Vioque, J.; MorenoGrau, J.M.; Ten, J.; Roca, M.; Moreno-Grau, S. and Bernabeu, R. (2010) A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics.

Fertility and Sterility. 93(4): 1128 - 1133

Fertility Update

IVF: Before, During and After

1.3 New Horizons in Embryology

Oludayo YUSUF

Abstract Since the birth of Louise Brown, there has been continuous development in assisted reproduction technology. Some aimed at better techniques and some at improving selection of gametes which leads to better embryos and possibly increased pregnancy rates. Research has led to the development of some techniques which are used routinely today in the field of assisted conception to achieve results and give hope to couples who desire to have children despite their diagnosis and challenges.

One of the major challenges in this branch of science is the pregnancy and implantation rate which is contingent on the quality of the embryos which are transferred. Embryo quality is itself contingent on many factors such as the quality of the sperm; position of the injection needle at intracytoplasmic sperm injection (ICSI), thickness of the oocyte and the factors that affect blastocyst selection. For these reason new technologies are aimed at improving the chances of pregnancy by developing, selecting and transferring the best blastocysts. Some of the technologies developed for this purpose are, Intracytoplasmic Morphologically selected sperm Injection (IMSI), Spindle view, Zona Imaging and EmbryoScope. IMSI allows the selection of the best sperms to improve the fertilisation and blastocyst development rates. With Spindle view and Zona imaging, the precision of the injection technique can be determined to improve fertilisation and blastocyst formation rates. The EmbryoScope focuses on recording the progress of the embryos during the culturing period with the hope of assisting in the section of the best embryo for transfer.

vacuoles and the number and size of these vacuoles indicates problem with the spermatozoa, especially problems with the DNA arrangements. With MSOME, it is possible to examine sperms at very high magnification (usually between 6000 and 12500 mag.). Viewing sperms at this magnification shows defects in sperm heads that cannot be seen with the ICSI microscope. It also enables the examination of the nuclear morphology of sperms and therefore aids selection. With IMSI, these sperms are selected against, ensuring that healthy sperms are injected into the oocyte.

IMSI is ICSI done at 6000 magnification objective instead of 400x objective of the ICSI Rig. This is possible because the Hoffman objective has been replaced with a Nomarski Differential Inference contrast (DIC) optics for better viewing and hence better selection. According to a study by Vanderzwalmen et al, where embryo development in 25 patient who underwent sibling oocyte injection with 4 different grades (Grade I â&#x20AC;&#x201C; IV) of spermatozoa, it was observed that there were no difference in embryo quality up to Day 3. However, the quality of the spermatozoa used affected the formation of blastocyst; and where grade IV (highly vacuolated) sperms were used, there was no blastocyst formation.

With this result, it could be said that IMSI can help to select the best sperms for injection and thereby improve pregnancy rates.

Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) One of such technique developed is Intracytoplasmic Morphologically selected Sperm Injection (IMSI). The aim of this technique is to select sperms of good quality and inject them directly into the egg. This technique was developed in 2004 by Benjamin Baartov of Bar- Ilan University in Israel. It is based on the principle of Motile Sperm Organelle Morphology Examination (MSOME) followed by ICSI. Through various studies, they were able to establish that human spermatozoa usually have

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Fig. 1A: Picture of sperms at 400 Magnification (ICSI). B: Picture of the same sperms at 6000 Magnification (IMSI)

Meiotic Spindle View Another technique used in assisted conception is the use of polarized light to assess oocytes before injection.

The quality of oocytes affects the fertilization and development of the resulting embryo. For this reason,

19

it is important to assess the quality of oocyte prior to injection. Some of the criteria used in the assessment of oocyte morphology include the evaluation of the cumulus complex, oocyte cytoplasm, polar body, perivitelline space, zona pellucida, and meiotic spindle. With the polarized light, it is possible to view exactly where the spindle of the oocyte is located and thus avoid damage while injecting.

During injection of an oocyte, it is assumed that the spindle is formed under the polar body of the oocyte and based on this assumption, oocytes are injected at right-angle to the polar body to ensure that the spindle is not damaged or distorted. However, some studies have shown that the precise location of the spindle may not be under the polar body as assumed. According to a study by Madaschi et al, it was observed that there was an increase in the fertilisation of oocytes when the spindle was visible compared to those that the visualisation on the spindle was not possible.

Zona Imaging Furthermore, polarized microscopy has also been used to view the Zona Pellucida of the oocyte and this is known as Zona Imaging (ZI). With ZI, the evenness and thickness of the Zona Pellucida is measured. This gives an idea of the quality of the oocyte and degree of nourishment it received from the follicle. This measurement is assigned a score which can either be positive or negative. A positive number implies that the zona is uniform, healthy and quality of the oocyte is good. However, a negative figure suggests that the zona is not properly formed and may indicate a problem with the quality of the oocyte. ZI imaging may be more beneficial in clients with advanced maternal age and can be used to determine the quality of oocytes prior to injection and also help advice the clients appropriately especially when the cycle fails. Madaschi et al also suggested that there is a positive correlation between spindle visualisation and the ZI scoring. This implies that the quality of an oocyte can be determined by using the two parameters prior to injection. However results with zona imaging are equivocal because the zonal thickness correlates with the cytoplasmic quality thus the poorer the egg quality the thicker the zona pellucida. Therefore although assisted hatching may improve implantation rate, it may not necessarily improve pregnancy rate.

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Fig. 2: Spindle view and Zona imaging of a Metaphase II oocyte.

EmbryoScope In vitro evaluation of embryos is an area in embryology that has improved greatly in the past decade with the major challenge being continuous monitoring of the zygotes until they become embryos thereby assisting in the selection of the embryo with the best implantation potential. To achieve this continuous monitoring and evaluation, various incubators fitted with digital cameras have been developed and one of such is the EMBRYOSCOPE. The EmbryoScope is an incubator with â&#x20AC;&#x153;in-builtâ&#x20AC;? camera designed by Unisense FertiliTech. The incubator is non-humidified and can monitor embryo development for up to five (5) days. The in-built camera takes photos of the embryos in culture every 20 minutes over the entire incubation period. The photos are archived in a database system and can be evaluated using the software program on the computer. With this technology, it is possible to monitor the development of the embryos in culture from the time of injection or insemination until they are blastocysts. During embryo development, the embryos go through various stages of cell division and the timing of these divisions is important. With time lapse assessment, it is possible to evaluate the embryo and the information may assist in the selection of the embryo with the best implantation potential.The EmbryoScope helps the embryologists to assess certain parameters for embryo selection such as the timing of first and subsequent cleavages, the synchrony of divisions and appearance of nuclei after division. It also detects multinucleation throughout the cell division progress.

The field of embryology is a continuously developing field where there are researches with the aim of selecting the best embryos and to increase pregnancy rates without

Fertility Update

IVF: Before, During and After

Fig. 3: The EmbryoScope

the complications of multiple pregnancies and births.

Although there is no single best way to conduct processes in the IVF laboratory, these available techniques could be used to achieve comparable results if used appropriately.

In addition, when choosing any of these techniques, key performance indicators should be set to monitor the processes and the outcomes.

For correspondence: fertilityupdate@thebridgeclinic.com

REFERENCES 1. Madaschi C, Aoki T, de Almeida Ferreira Braga DP, de CรกssiaSรกvioFigueira R, Semiรฃo Francisco L, Iaconelli A Jr, Borges E Jr. (2009) Zona Pellucida Birefringence Score And Meiotic Spindle Visualization In Relation To Embryo Development And ICSI Outcomes. Reproductive Biomedicine Online, 18(5):681-6.

Madaschi C, de Souza Bonetti TC, de Almeida Ferreira Braga DP, Pasqualotto FF, Laconelli A Jr, Borges E Jr.(2008) Spindle imaging: a marker for embryo development and implantation. Fertility and Sterility. 90(1):194-8.

Rama Raju GA, Prakash GJ, Krishna KM, Madan K. (2007) Meiotic Spindle and Zona Pellucida Characteristics As Predictors Of Embryonic Development: A Preliminary Study Using Polscope Imaging. Reproductive Biomedicine Online.14 (2):166-74.

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1.4 The Bridge Clinic partners with IVF clinics Professor Zech

O. J. Dibosa-Osadolor

The Bridge Clinic introduced the fundamentals of in-vitro fertilisation (IVF) to Nigeria in 1999. Our objective then was to create the infrastructure that would allow us to carry out IVF within the limitations of a non-purpose built premises. We implemented a quality management system (QMS) in 2004 to enhance our value proposition to our patients and we are proud to say that we have developed and sustained the technology of IVF over the last 13 years. This includes the opening of new clinics across the country, as well as creating a template that has formed the basis of the expansion of the IVF industry in Nigeria.

The technology of IVF is rapidly advancing and the best clinics in Europe are able to achieve pregnancy rates of over 50% across all age groups which is more than double the pregnancy rates that we are able to achieve in Nigeria. There are many reasons for this variance in treatment outcomes which can be deliberated on according to the following categories; patient characteristics, clinical processes, laboratory processes and quality management systems.

The objective of this article is to provide an overview of the current thinking about optimizing pregnancy rates in IVF and define what we aim to achieve by our collaboration with the IVF centres Prof. Zech.

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The IVF centres Prof. Zech, formerly called the Institute for Reproductive Medicine and Endocrinology, was founded in Bregenz, Austria in 1984 by Univ. Prof.

Dr. med. Herbert Zech. Prof. Zech is a professor at the University of Innsbruck and scientific director of the IVF Zech group. He commenced operations in Bregenz, Austria when the revolutionary science of IVF was still in its infancy. With ground breaking research and a dedication to his vision of â&#x20AC;&#x153;giving new life to loveâ&#x20AC;? the IVF Centres Prof. Zech have become internationally renowned leaders in the field of reproductive medicine with multiple clinics in Bregenz and Salzburg in Austria, Czech Republic, Italy, Switzerland, Liechtenstein and the birth of over 25, 000 babies from these centres. With one of the highest pregnancy rates on the league tables they have earned and secured their place as leaders in the industry. Prof. Zech and his team also recognised the important role of total quality management in healthcare and they were the first clinic in the world to implement the international organisation for standardisation (ISO) standards to the field of reproductive medicine. Currently driving operations in his capacity as Medical Director is Dr. Nicholas Zech, also a specialist in gynaecology with subsequent subspecialisation in reproductive medicine and a pace

Fertility Update

IVF: Before, During and After

setter in scientific research and innovation, the IVF Centres Prof. Zech have contributed immensely to the field with numerous publications in international journals and technological advancement. Prof. Zech is a member of numerous international scientific boards and associations and has been the honorary president of the “Österreichische Gesellschaft für Reproduktionsmedizin und Endokrinologie” (Austrian Society for Reproductive Medicine and Endocrinology).

Their philosophy of optimizing stimulation protocols; the use of automated 3-dimensional ultrasound technology to enhance the timing of hCG injection, stringent attention to egg collection techniques to ensure the quality and yield of oocytes as well as an innovative embryo transfer technique are just a few examples of the clinical aspects that have contributed to the high pregnancy rates seen in IVF centres Prof. Zech.

The quality management systems that they run in the laboratory are one of the most advanced in the world. This as well as cutting edge research to

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refine the application of new techniques such as vitrification of oocytes and embryos; intra-cytoplasmic morphologically selected sperm injection (IMSI) and spindle view to optimise fertilisation rates as well as constantly researching techniques to assist with the selection of the best blastocyst for transfer such as the EmbryoScope have contributed to the fantastic pregnancy rates.

The quality management of all these processes as well as the equipment, stock management and batch control are all managed on an electronic platform called DynaMed. The Bridge Clinic’s collaboration with IVF centres Prof. Zech provides us access to all these innovative, cutting edge developments in IVF with our staff going over to Austria for training and their staff coming over to Nigeria to further enhance the training and development of TBC with the clear objective of benchmarking all our KPI’s with the excellent results achieved in Bregenz.

The objective of the collaboration is to enhance

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the quality of services that we deliver to our patients in Nigeria and ensure that these services meet the same standards as would be available anywhere internationally. This is in line with the philosophy of TBC to operate to world’s best standards.

The Bridge Clinic, under the stewardship of Dr. Richard Ajayi, pioneered focused fertility clinics in Nigeria over 13 years ago. By applying appropriate technology and demystifying in-vitro fertilisation (IVF) we have made significant contributions to maternal health in Nigeria by the provision of safe and reliable fertility treatment across the nation. We currently have 5 clinics including the Institute of Fertility Medicine (IFM), a corporate social responsibility initiative in collaboration with the Lagos State University Teaching Hospital (LASUTH), to give socio-economically disadvantaged couples access to safe and quality IVF services. Similar to our international partners, we were the first clinic in Nigeria to implement a quality management system with our ISO accreditation by TŪ√ Austria in 2004, ahead of most clinics in the United Kingdom. We have continued to drive our ethos of quality management in healthcare with our campaigns in the last 2 years by calling for regulation of the IVF industry in Nigeria. The benefits of this collaboration are: a) Access to new treatment modalities and techniques The IVF centres Prof. Zech are renowned for developing, establishing and implementing new technologies in reproductive medicine in order to better the couple’s chances of achieving pregnancy and delivering a healthy baby within the shortest time “as early as the first treatment cycle” possible.

They have thus pioneered inter alia the blastocyststage culture of embryos; embryo diagnostics using the EmbryoScope and 24Sure Genetic screening which provide detailed analysis and assessment of embryonic development.

Critical to the success of the IVF procedure is the selection of the best sperm cells for fertilisation of the egg. This was previously achieved by the revolutionary process if intracytoplasmic sperm injection (ICSI) which was pioneered in 1992. This process has been enhanced by the novel process of intracytoplasmic morphologically selected sperm injection (IMSI) which allows for more

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advanced sperm assessment and subsequent selection as the spermatozoa are viewed a higher magnification. , Other treatment techniques include the optimization of freezing eggs and embryos using aseptic vitrification, the objective evaluation of follicular development according to standardized operating procedures to name a few. These will be available to patients within The Bridge Clinic infrastructures. b) Quality management systems The IVF centres Prof. Zech have imbibed a strong culture of quality management as a consequence of their history of being the first fertility clinic to deploy a quality management system according to ISO standards with their current certification being awarded by Quality Austria. With this ethos of quality, the IVF centres Prof.

Zech is committed to providing excellent care to their clients while assuring them of the highest pregnancy rates and quickest “time to pregnancy” in an environment of safety, care, expertise and utmost professionalism.

This is achieved by the seamless integration of their operational and support processes by the development, deployment and implementation of an enterprise resource planning application called DynaMed. c) DynaMed DynaMed is a proprietary enterprise resource planning (ERP) application developed by Ima Systems specific for IVF centres. It is a bespoke electronic platform which combines the benefits of being an electronic medical record with an excellent interface with business support. The Bridge Clinic has successfully implemented DynaMed in the last 3 years and this makes it easier for us to harmonise our patient monitoring, cycle review and performance management processes across multiple clinics in multiple locations. This has been critical to our strategy of opening multiple clinics.

It gives us a platform for reviewing patient records across all our locations and robust decision making. The application extends itself by being a central repository of information on all standard operating procedures (SOPs) which are accessible to all members of our team in all locations so that patients are managed according to the same guidelines, processes and treatment protocols. It serves as a platform for managing performance of all operational and support processes.

Fertility Update

IVF: Before, During and After

d) Stock and supply chain management By collaborating with the IVF centres Prof. Zech we will be exposed to top of the range medical and laboratory stock and consumables which will be supplied to us by ISO certified vendors, who share our mutual quality ethos, under the best conditions within the best logistics support processes. e) Research and development The Zech Group is at the cutting edge of research and development which cuts across all facets of health technology from pharmaceuticals, to new treatment processes, to exploring the contributions of alternative healthcare to treatment success and equipment. All decisions made on patient care are evidence-based and there is a continuous spirit of research with the objectives of bringing new and emerging technologies to the fore and making them accessible to their patients. The Bridge Clinic will be part of this culture and our patients will benefit from novel technological advancements geared

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at giving them their best chances of achieving a pregnancy. f) Knowledge sharing and skill transfer This collaboration affords The Bridge Clinic team the benefits of knowledge and skill transfer from one of the best centres in the world with pregnancy rates of 70% to 80% in women under 35 years and quality management systems which ensure that these outcomes are continuously improved upon. Our team will have the benefits of working in their centres for varying periods of time and their teams will come to our clinics and work with us with the objectives of harmonizing our levels of expertise and service provision with theirs.

We, at The Bridge Clinic, made a strategic decision in 2004 to implement a quality management system which would differentiate our services and assure our clients that they are in the right place. We have furthered this by collaborating with one of the best centres in Europe so that we may keep our vision alive.

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...F a c i l i t a t i n g

Specialised Medical Care in South Africa.

While we recognise the fact that Nigeria and other West Africa Countries are endowed with competent health professionals; the need for patient referral for specialised treatment abroad may arise on occasion.

AFRIsurg is your chosen health partner which assures you (and your patients) of this opportunity.

Our dedicated team of health professionals combine their wealth of experience and expertise to provide these specialised health care services to people in need with over five hundred clients to date who have benefitted from these services.

Our comprehensive care programme includes: S Evaluation of the medical needs of the patient before departure.

S Advice on cost of medical care and global fee arrangements.

S Appointments with the right medical experts.

S Visa applications for entry to South Africa.

S Accommodation for patients and their care givers.

S Coordination of Airport shuttle services and local transportation for hospital visits.

We endeavour to make the journey to South Africa as comfortable and cost effective as possible, while assuring you of the best standard of care.

63, Oduduwa Crescent, G.R.A. Ikeja, Lagos.

Tel: 234-1- 4485 412, 702 880 6812 E-mail: info@afrisurgwa.com www. afrisurgwa.com

Breaking through infertility

since 1999

BB PIN: 29971D19

Your cherished patients

deserve the best

When making a referral, a doctor trusts that their patients will receive the highest quality of service. A partnership with The Bridge Clinic gives peace of mind that our internationally recognised quality standards guarantee only the best for your patients.

Lagos: Plot 1397A Tiamiyu Savage Street, Victoria Island, Lagos. P.O. Box 70294.

Ikeja: 63, Oduduwa Crescent, G.R.A. Ikeja, Lagos.

Port Harcourt: 41A Evo Road, G.R.A Phase II, Port Harcourt Rivers State.

www.thebridgeclinic.com Tel: 01-461 9006, 08104607790 and 08104607791 enquiries@thebridgeclinic.com

Kaduna: 26 Kinshasa road, Ungwar Rimi, G.R.A. Kaduna North, Kaduna State

We operate to worldwide best practice standards