Role of GPs in changing landscape of fertility treatment

PRIMARY care has for years been the cornerstone of the Australian health care system and GPs represent an integral part of it. As they are frequently responsible for the first, and sometimes only, contact of individuals with the health care system, they can profoundly affect a patient’s experience, expectations and optimise health outcomes.

In the domain of reproductive health, GPs have a crucial role as they can improve pre-conception health and, importantly, diagnose and refer patients affected by infertility.

Optimisation of reproductive health begins by informing patients on how they can best meet their reproductive goals at different stages of their life. Patients who wish not to conceive can be offered appropriate contraceptive options therefore avoiding unplanned pregnancies and sexually transmitted infections that can have a long-lasting effect on their fertility.

Those who wish to conceive can receive advice on the enhancement of pre-conception health, such as by adopting a healthy diet and maintaining a healthy weight, exercising regularly and taking pre-conception supplements (including folic acid or iodine).

Importantly, all individuals seeking fertility advice should be educated on the potential negative effect of advancing female age on the quality and quantity of a woman’s oocytes and, therefore, on her fertility.

These have traditionally been important roles of GPs in the primary prevention of infertility and the overall enhancement of reproductive health. Nevertheless, in the past two decades there have been important scientific discoveries that have transformed the landscape of fertility management. To maximise the benefit of these developments for patients, the role of GPs is today more important than ever.

Pre-conception genetic carrier screening: everyone should know

There are a large number of inheritable diseases with an early onset and a devastating impact on a child’s health, quality of life and/or life expectancy. Any individual, even if unaffected themselves or with no relevant family history, can be a carrier of specific genetic information (mutations) that can be passed on to their offspring and increase the risk of them having such a disease. Next generation sequencing of DNA is a technology that has allowed for the development of efficient and affordable panels of genetic screening for hundreds of diseases using a simple blood test or a buccal swab.

The implementation of a population-wide, genetic carrier screening program aims primarily at reducing the incidence of serious genetic disease in a couple’s offspring. This can be performed by identifying couples that are at a high risk of having an affected child and facilitating informed decision making regarding their reproductive options.

These options include:

  • conceiving a child naturally and testing them after birth to see whether they are affected by this condition;
  • conceiving a child naturally and performing prenatal diagnostic testing (usually in the form of chorionic villus samples or amniocentesis) to determine if the fetus is affected. If they are affected the patients might need to consider whether they will proceed with the pregnancy or not;
  • to have in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD), which will allow them to test the embryos before implantation in order to significantly reduce the probability of having a pregnancy with an affected fetus;
  • to use donor sperm or eggs;
  • to proceed with adoption; or
  • to decide not to have children.

The importance of genetic carrier screening has been acknowledged recently in Australia. In 2018 the federal government announced Mackenzie’s Mission, a research program aiming to investigate how screening can be offered to couples who wish to access it. Moreover, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) issued a recommendation in 2019 stating that “Information on carrier screening for other genetic conditions should be offered to all women planning a pregnancy or in the first trimester of pregnancy”. Importantly, since November 2021, the Australian Government has introduced funding of pre-implantation genetic testing for eligible couples through a relevant listing on the Medicare Benefits Schedule.

It becomes clear that genetic carrier screening is now an important part of the peri-conceptional counselling in Australia. As such, GPs play a crucial role in counselling patients on their options and need to remain up to date with the relevant guidelines or policies.

The role of antimullerian hormone (AMH) in fertility screening: use responsibly

AMH is secreted by the preantral and small antral follicles in a woman’s ovaries. These are the follicles that will be recruited during the subsequent one or two menstrual cycles and have been shown to be correlated with the number of resting follicles in woman’s ovaries, that is, her ovarian reserve. Therefore, the determination of serum AMH using a simple blood test has been marketed by many as an “egg timer” or a test that can reveal a woman’s fertility. Not surprisingly this has led to a widespread use of this test even by GPs, very commonly upon the request of their patients.

Recent evidence, however, has convincingly demonstrated that the result of this test cannot predict a woman’s fertility nor her chances of a pregnancy and, therefore, its interpretation is not as a straightforward as it was originally thought.

An unexpectedly low AMH can cause a lot of distress to individuals as they will usually, incorrectly, interpret it as evidence of reduced fertility. On the other hand, a relatively high AMH in women of advanced reproductive age might offer false reassurance regarding their fertility and lead to significant delays in having children.

GPs, once again, are vital in ensuring appropriate use and interpretation of such a test along with establishing clear referral pathways for their patients to fertility specialists.

From fresh to frozen: the new paradigm of IVF

Despite the fact that IVF represents a relatively new field of medicine, it has exhibited a remarkable advancement in terms of the technology used. It would not be a hyperbole to claim that a modern IVF cycle has little in common with how a cycle was performed during IVF’s early days, in the late 1970s.

For years, the focus of an IVF cycle was to stimulate the ovaries and obtain a reasonable number of oocytes while ensuring the patient was not hyperstimulated and creating a small number of competent embryos. The best of these embryos would then be transferred back into the uterus a few days after the oocyte collection in order to achieve a pregnancy. Any supernumerary surviving embryos of good quality would then be cryopreserved in order to be used in the future.

During this era, the success rates were low and IVF was associated with an increased chance of multiple pregnancy, which is known to be associated with significant risks for the mother and the babies.

Australia and New Zealand were among the first countries to implement the widespread use of single embryo transfer, which has led to a dramatic decrease in the number of multiple pregnancies after IVF. This change was not easy but was achieved due to a well coordinated effort by GPs, nurses, counsellors and fertility specialists to educate patients on the benefits of single embryo transfer.

Today, the paradigm of IVF is once again changing by moving away from the fresh embryo transfer to improve efficiency and safety even further. Arguably the most important scientific development that allowed the implementation of safer and more efficacious protocols has been vitrification — a method of oocyte and embryo cryopreservation with remarkably high survival rates, especially compared with slow freezing, which was the traditional method of embryo cryopreservation in IVF.

It is revealing to observe that, according to data from the Australia and New Zealand Assisted Reproduction Database (ANZARD), as the use of vitrification started increasing during the period 2009–2013 (from 33% in 2009 to 83% in 2013), so did the success rates of cycles involving frozen-thawed embryos (from 18.3% to 23.4%).

At the same time, data started surfacing suggesting that a fresh embryo transfer is sometimes associated with lower chances of pregnancy, particularly in cycles with many oocytes retrieved due to a compromised endometrial receptivity. Other evidence (here and here) suggested that pregnancies achieved after a fresh embryo transfer are at higher risk of certain obstetric complications such as ectopic pregnancy, abnormal placentation, preterm delivery and babies small for gestational age.

All this evidence has formed the basis of a significant change in clinical practice, with an increase in the number of cycles where a fresh transfer is avoided, and all competent embryos are cryopreserved (“freeze-all”). In Australia and New Zealand, there has been an 126% increase in freeze-all cycles between 2014 and 2018.

As these changes continue to transform how IVF is performed, GPs need to play a key role in informing patients of these new developments and their benefits. This is particularly important as it has been recently shown that patients value the opportunity to plan their treatment in advance and this eventually can lead to improved experiences for patients as well as superior and safer outcomes.

Associate Professor Venetis is a Senior Research Fellow at the Centre for Big Data Research in Health at the University of New South Wales, a practising fertility specialist, and the Director of Clinical Research for IVFAustralia in Sydney.

 

 

The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.

Ersuchtihn | Faery Wicca | Financial Planning Experts | Free Baby Samples |