Beyond the Mediterranean diet: Improving IVF success in women with higher BMI

Being a healthy weight, eating a varied diet with plenty of fruit and vegetables, taking regular exercise and cutting down on alcohol – this is all good advice for everyone. But the direct influence on these factors on the fertility of both men and women, highlighted this week by a study suggesting a 'Mediterranean diet' in women can boost IVF success rates (see BioNews 936) is now becoming better understood.

One example where weight impacts fertility is Polycystic Ovary Syndrome (PCOS), which affects 5-10 percent of women. PCOS is a complex syndrome that produces a wide variety of symptoms, such as acne, hirsutism, menstrual irregularities, obesity and glucose intolerance, that are present in some women and not in others. This makes it difficult to both diagnose and treat.

I often find that women with PCOS have had their symptoms treated by different specialists over a number of years. For example, acne is treated with antibiotics and menstrual disturbances with the contraceptive pill.

As the pill often masks the symptoms, it is only when they have failed to conceive that the PCOS has been correctly diagnosed. Sadly, by this time many have an increased BMI (body mass index), which often makes fertility treatment less effective and pregnancy more of a problem.

What is now emerging is that PCOS is associated with a metabolic disturbance, which is characterised by insulin resistance and high levels of insulin in the blood. In some women, raised insulin levels impacts the ovaries, preventing them from releasing mature eggs, and so leading to infertility.

PCOS can be diagnosed with blood tests for serum testosterone, LH (luteinising hormone) and FSH (follicle stimulating hormone) supported by ultrasound, which reveals the immature follicles on the surface of the ovary.

The metabolic imbalance can also make it difficult to lose weight and it is not unusual for women with PCOS to report a history of weight problems, obesity, rapid weight gain, and if this is left unchecked it can increase the risk of pre-eclampsia, gestational diabetes, high blood pressure and miscarriage. It can also raise the risk later in life of developing diabetes and heart disease.

These long-term health implications make accurate diagnosis and early treatment even more important; not just for fertility but for the health of the woman during pregnancy and beyond. The encouraging news is that early detection and lifestyle management can greatly improve their overall health and boost their natural fertility.

With the right support women can lose weight ahead of fertility treatment and evidence from our clinic and the literature suggests that this is very effective. One study found that in obese women where ovulation has ceased, a 5-10 percent weight loss restored ovulation to over half the women within six months.

If lifestyle management alone is not sufficient to restore ovulation then stimulation with anti-oestrogens such as clomiphene citrate remains the treatment of first choice. But this needs to be carefully monitored, preferably with ultrasound.

Where IVF is required the NICE guidelines state that women should have a BMI of 19-30, and ideally below 25, to be eligible for IVF treatment. This is because women with a BMI of between 25 and 30 have lower success rates when all other factors are equivalent.

Little is known about the effect of ovarian stimulation drugs on this group of women, as most trials focus on women with a BMI of 19-25, and those with a higher body weight are typically excluded. Ovarian stimulation is used to increase the number of recruited eggs for IVF.

The types of drugs and their timing are defined by protocols. There are two main protocols, LDP (Long Downregulation Protocol) where down-regulation is used to control the woman's natural cycle, followed by ovarian stimulation to increase egg production. The other is Antagonist Protocol, which uses ovarian stimulation without prior down-regulation. Instead, an antagonist drug is introduced during the course of stimulation to prevent ovulation and, therefore, allow the retrieval of eggs for IVF.

We are fortunate at Bourn Hall, founded by pioneers Dr Patrick Steptoe and Professor Robert Edwards, that as the world's first IVF clinic we have data going back nearly 40 years. We used this historical data to compare success rates for two widely used IVF protocols, LDP and Antagonist Protocol and the results were very interesting.

The study compared the outcomes of women with an average BMI of 22 with those of 27 for each protocol. All other factors, including age, cause of subfertility, previous IVF treatment, starting stimulation dose, use of ICSI technique and number of embryos transferred, were accounted for.

Women treated with the LDP protocol showed a significant difference in pregnancy rates. The lower-weight group had an average 45 percent pregnancy rate compared to 31 percent for those with a higher BMI. However, the success rates for the two groups treated with the Antagonist protocol were similar: 41 percent for those of the lower weight compared to 39 percent for the higher weight group.

Both protocols are widely used during IVF. The LDP protocol has been historically the 'gold standard' protocol in IVF.  Bourn Hall Clinic was instrumental in the development of this protocol during the early years of IVF. However, when these early protocols were developed, only a small minority of the population had a BMI of over 25 (defined by the BMI healthy weight calculator as 'overweight'). Now many more women are in this category and this could impact on the effectiveness of the drug protocols.

The study also suggests that the lower success rates achieved for these women during IVF may not be just as a result of the 'obesity factor', but instead that outcomes for this group can be improved through the improved selection of stimulation protocol.

This study provides new information suggesting that protocol selection should be weight-adjusted, as this will likely maximise IVF success for this group of women.

A balanced and healthy diet with less refined carbohydrates and fats and less alcohol consumption can benefit both men and women and help tip the balance where subfertility of both partners is affecting conception. However, for those who are struggling to lose weight these findings give encouragement and also provide health professionals with some new insights into fertility care.