Indian Fertility Society Good Clinical Practice PCOS Guidelines

Abstract

Sonia Malik is President of the Indian Fertility Society, Chair of the Infertility Committee of FOGSI, Chair of the Scientific Committee of IFFS 2016, Scientific Collaborator at the Reproductive Research Centre at the Cleveland Clinic (USA), Past President of the Indian Menopause Society and Co-Editor in Chief of the Journal of Midlife Health. Her areas of interest cover reproductive endocrinology, reproductive immunology, genital tuberculosis and premature ovarian failure.

Q Dr Malik, you are the President of the Indian Fertility Society; please can you tell our readers a little about the work of the society & how you became involved in it?

The Indian Fertility Society (IFS) was founded in 2005 with the intention of promoting academics and good clinical evidence based practices among clinicians practicing infertility management in India. Those were the formative years of infertility management in the country and there was neither any formal training available, nor practice guidelines. I am one of the founder members. It has taken us a decade to put things together because the country is large with lots of diversity. However, the society now has a truly national and international stature, with its own publications and training programs in the form of a newsletter and journal, a training program for embryologists and its own clinical fellowship. The society runs workshops, multicentric trials on different aspects of infertility across the country and as a distant learning initiative, have just incorporated webinars into the curriculum. We have taken a lead in the country by publishing the first practice guideline on the management of polycystic ovary syndrome (PCOS) in the country. The society is now poised to host the world congress of the International Federation of Fertility Societies in 2016. We are confident that we shall gradually be able to achieve the goals that we have set for ourselves.

Q The IFS has recently published guidelines on polycystic ovary syndrome: what are the most important recommendations regarding diagnosis of PCOS?

The Indian guidelines have been formulated using the Indian studies on the subject. We have observed that in the Indian context, both the Rotterdam and NIH criteria have been used in the studies but the disorder has been better picked up using the Rotterdam criteria. The Indian phenotype also varies from region to region within the country. However, considering that majority of our population is rural and the doctors serving in these areas have minimal facilities, we have emphasized on ‘risk factors’ which should make the practitioner suspect the condition and enable him to refer to a higher center. The guidelines also take cognizance of the fact that Type II diabetes and metabolic syndrome are very common in the country – even in adolescents, hence need to be looked for while dealing with an Indian polycystic ovary patient. Also, we have tried to use the Indian published criteria from other societies in diagnosing PCOS – for instance, the modified Ferriman–Gallwey scale as recommended by the Indian Dermatology Association for the diagnosis of hirsutism. So, to summarize, the Indian guidelines recommend one clinical and one biochemical index as a risk factor for developing PCOS, especially in adolescents and such patients must be kept under surveillance or referred to a higher center for further evaluation.

Q And what about recommendations regarding treatment of PCOS?

The highlight of our guideline is that we have quoted and taken into consideration the Indian studies for each segment all through but also compared them with the International guidelines. And wherever we have not found robust evidence from our own studies, we have made standard recommendations from the other guidelines. Therefore, the recommendations regarding treatment are similar to those used in the other international guidelines. However we have tried to define the maximum limit for the use of hormones as 2 years, especially in children and the elderly PCOS keeping in mind the high incidence of thrombophilia's in the country. A lot of emphasis has been given to diet and exercise.

Q Are there any controversial sections to the guidelines? If so, why are they controversial?

There are of course many controversies and challenges when dealing with a PCO patient. In fact there are many questions that are still unanswered in this context. For instance, insulin resistance is the prime factor for the development of this disorder but insulin measurement is not mandatory to make a diagnosis of PCOS. Similarly, the controversy of using metformin in pregnancy is addressed. Clinicians believe that it helps to prevent miscarriages but evidence is lacking and none of the guidelines including ours recommends its use in pregnancy.

Similarly, prescribing hormones for long may be harmful, as we have seen in the case of hormone replacement therapy in menopausal women. The question of when to start and when to stop hormone therapy in these patients is still a query.

There is also the controversy of the thrombosis prone PCO. So, should all patients be screened for coagulopathies given that they have to be prescribed hormone therapy for long duration? The question still is unanswered.

Q What are the main challenges facing researchers in the PCOS field, & what about challenges for clinicians?

Evidence-based medicine demands randomized controlled trials to prove hypothesis and that is not always possible in human subjects. This is one of the biggest challenges. There are many gray areas in PCOS research and clinical application for this reason. Although a lot of clarity is now there as far as phenotypes are concerned, the biggest challenge is to find the exact cause for the disorder. It is also important to understand the evolution of the disorder. What exactly causes hyperinsulinemia and when it begins is not clearly understood. Research now points toward the origin in the prenatal period. The challenges therefore would be to define the pregnancy diet, life style and drug interventions for women who are prone to or having PCOS in order that it is not passed on to the progeny. Similarly, infertility management though fairly standardized may not give the same success rates in all types of PCOS. Developing algorithms is a challenge since the exact cause and evolution of the syndrome is not very well known.

Q How do you see the diagnosis & management of PCOS changing over the next 5–10 years?

This is a remarkable time for scientific research and advancements. In fact the last two decades have changed scientific thought completely. With the advent of genetics and epigenetics, PCO research has a new dimension now. We are gradually becoming aware of the development of various phenotypes due to genetics, diet and environmental influences. Weight is supposedly one of the biggest influences in the development of the disorder and lifestyle and diet is the mainstay of management for this. A lot of research is going on to find the correct long-term diet for such patients. Bariatric surgery is also slowly gaining importance as a treatment modality in grossly obese PCOS patients. However, the long-term effects of bariatric surgery on the health and weight of the individual are still unknown. Recent developments in pharmacogenomics may provide clues to the relationship between response to drug therapy and the underlying individual genetic makeup. There is emerging evidence that women with PCOS exhibited a variable response to metformin based on the polymorphism in the STK11 gene. It is therefore a possibility that diagnosis and treatment protocols may be defined based on the genotype and phenotype of the patient.

Presently, with the diagnostic criteria and guidelines now in place, many things are clear but a lot needs to be done in order to bring uniformity in management among clinicians from different specialities. Today, gynecologists are looking at the disorder differently than the endocrinologists or the pediatricians. I am confident that in the coming years we will have dedicated PCOS clinics where all concerned clinicians would be working together.

Q Are there any particularly exciting areas of research within the realm of women's fertility in general that you would like to discuss briefly?

Infection and inflammation is probably the most common but underdiagnosed part of infertility. Very little is known about the changes that come about as a result of these factors. Gene modulation as a result of inflammation is a cause for concern. There is an urgent need to look into the immunology of infections and its impact on reproductive health. Chronic infections like genital tuberculosis are rampant in lesser-developed parts of the world and who knows they maybe associated with hormone disorders like PCOS as well!

Endometriosis is another enigmatic disease of the disordered immune system that seems to be increasing due to stress and lifestyle. Although infertility management in endometriosis is fairly well defined, there are still gray areas remaining. Oocyte quality, embryogenesis and quality and poor implantation are challenges. Many times endometriosis and PCOS may co exist leading to further complexities in management and outcomes.

As we delve into the various fertility disorders, we seem to be realizing the important role of the immune system. Clinicians however are not very well versed with the nuances of the immune system hence more clinical research is required in this area for better reproductive outcome.

Q How do you see management of female infertility changing in general over the coming years? What are the main obstacles to overcome?

Assisted reproduction technology has revolutionized reproductive medicine. With better understanding of the process at molecular level and a perfect blending of basic sciences and clinical application, management of infertility will change completely. Fertility preservation has already begun to change the infertility scenario. Treatment has now been extended to the fertile normal couples as well in the form of social oocyte freezing so that they can reproduce at will. This is also a boon for cancer patients. The newly discovered autologous mitochondrial transfer maybe a lease of life for patients suffering from premature ovarian aging. With stem cells and gene therapy just round the corner, the need for third party reproduction should decrease. Pregnancy after uterine transplant is a reality now and in the coming years more such cases would be seen thus giving respite to those with uterine factor infertility.

More research is however needed to achieve excellence in this field before these can be clinically applied. Presently, the major obstacle is lack of self-regulation and ethical practices among the doctors due to which new innovations are immediately applied to patients without knowing the long-term repercussions of treatments. It may not be wise to apply all basic science research to clinical practice due to lack of experience with such practices. In our enthusiasm to better infertility outcomes we need to be cautious that we do no harm to the patient.