Is IVF a real solution for infertility caused by PCOS?

In this webinar, Dr Laura Garcia de Miguel, MD, Medical Director at Clinica Tambre, explains PCOS in detail and talks about fertility solutions for female patients affected by this health problem.

What is PCOS

Polycystic ovary syndrome (PCOS), which affects 1 in 10 women of reproductive age, is one of the most common endocrinological disorders. It happens when ovaries – that regularly develop numerous small collections of follicles – fail to regularly release eggs during ovulation. This results in hormonal imbalance and metabolism problems that may affect women’s overall health and appearance. Some of the most common PCOS symptoms are hair loss or its opposite – hirsutism, pelvic pain, overweight, acne, high testosterone levels and irregular periods. The latter may lead to infertility.

Possible causes of PCOS

Dr Garcia explains that the exact cause of PCOS is still unknown. Experts think that many factors may play a role. PCOS is thought to be often related to insulin resistance. Insulin resistance is when the body’s cells do not respond normally to insulin. As a result, a woman’s insulin blood levels become higher than normal, which, in turn makes the ovaries produce too much testosterone. Too much testosterone interferes with the development of the follicles and prevents normal ovulation. Another possible cause is hormonal imbalance. It is understood not only as raised levels of testosterone but also as high levels of luteinising hormone (LH). Normally, the latter stimulates ovulation, but if its levels are too high, it may have an abnormal effect on the ovaries. Hormonal imbalance causing PCOS may refer to low levels of sex hormone-binding globulin (SHBG) as well. SHBG is a protein in the blood, which binds to testosterone and reduces its effect. Additionally, Dr Garcia mentions a genetic cause of polycystic ovary syndrome. It is true that PCOS sometimes runs in families. It means that if any female relatives of yours (such as your mother, sister or aunt) have PCOS, the risk of you developing it is increased, too.

How PCOS is diagnosed

When it comes to the way PCOS is diagnosed, there is no single way either. Dr. Garcia mentions a pelvic ultrasound that is used to diagnose all the small follicles in ovaries – women affected with PCOS can have more than 12 follicles accumulated in each ovary. Then, there is also a hormonal blood test conducted to check for abnormalities of sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), androstenedione, oestradiol (oestrogen), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Women who are not affected by PCOS have twice as much FSH as LH. By contrast, PCOS patients have increased LH levels – as compared to FSH. In addition to the above, there is also the need to do the glucose metabolism/tolerance blood test, as well as tests showing the risk of cardiovascular disease. Dr. Garcia explains that in PCOS patients, there is always the possibility of having increased cholesterol and blood pressure. What is more, women affected by PCOS are more likely to have thyroid disorders. In their case, the prevalence of subclinical hypothyroidism and thyroid autoimmunity is increased. That’s why it’s highly important to check the thyroid function in these patients (with a blood test for TSH, T4 and antithyroid antibodies).

Non-pharmacological and pharmacological interventions

As it was mentioned before, PCOS negatively impacts fertility. Women with this condition do not ovulate regularly, their periods become irregular and increased levels of hormones such as testosterone affect their eggs’ quality. However, getting pregnant is still possible – but it often requires serious lifestyle modification and pharmacological interventions. According to Dr Garcia, the first step is the so-called non-pharmacological interventions, including a healthy diet and exercise. Dr. Garcia admits that if a PCOS patient is of healthy weight, it is much easier to regulate her ovulation. That’s why it is recommended to use a low-calorie diet with adequate nutritional intake and healthy food choices. It is also very important to do exercise – a minimum of 150 min/week of moderate intensity physical activity or 75 min/week of vigorous intensity and muscle strengthening activities on 2 non-consecutive days/week. For a modest weight loss, a minimum of 250 min/week of moderate intensity activities or 150 min/week of vigorous intensity activities is recommended. All of it helps to improve the metabolism of glucose and makes the ovaries work much better. The second way that women affected with PCOS can boost their fertility with is the pharmacological intervention. Dr. Garcia says there is the possibility of using oral ovulation induction agents, such as Letrozole or Clomiphene Citrate. The first one is administered at 2.5 to 7.5 milligrams daily for five days. Many studies show that Letrozole is a superior drug to Clomiphene Citrate in terms of clinical pregnancy rate and live birth rate. However, Clomiphene Citrate is used more frequently. It is administered typically for five days, starting on the second day of the period. A course of three to six cycles of oral ovulation induction is recommended in such a case. Another pharmacological solution for PCOS patients is Metformin. It is a drug that inhibits hepatic glucose production, decreases intestinal glucose uptake and increases insulin sensitivity in peripheral tissues. Dr. Garcia admits that it plays an important role in improving ovulation induction in women with PCOS. Metformin is available as 500-, 850- or 1000-mg tablets, with an average dose of 1500 mg per day. Metformin may be used as an adjunct to other ovulation inductions agents or by itself in women with PCOS and with no other fertility factors. Regarding pharmacological interventions, there is also the possibility of using ovulation induction with gonadotropins. Dr. Garcia says there are various preparations of gonadotropins for therapeutic use with FSH and LH effect. They are used as second-line agents for ovulation induction, following unsuccessful treatments with first-line oral ovulation induction agents. However, it’s very important to remember about careful monitoring of the treatment cycles with serial ultrasound scans to avoid multiple pregnancies.

The use of or ART for PCOS

When neither non-pharmacological or pharmacological interventions prove to be helpful in achieving pregnancy, many PCOS women need to seek care from fertility specialists. Dr. Garcia mentions two of the assisted reproductive techniques used in such cases: IUI (intrauterine insemination) and IVF (in vitro fertilisation). In IUI, sperm, which has been washed and concentrated, is placed directly in the uterus right after the ovulation. The technique doesn’t need to be performed under anesthesia and is a relatively painless and non-invasive procedure. In IVF, the woman has medicines given to stimulate the ovaries to produce eggs. The eggs are then collected and mixed with sperm in a laboratory. If fertilisation is successful, the embryos are left to develop for between 2 and 6 days. This helps to select the strongest embryo, which is then transferred back to the woman’s uterus to implant. Dr. Garcia says that this moment is carried out with the monitoring scan to leave the embryo in the correct place. If there are other good quality remaining embryos, they will be frozen. 10 days after the embryo transfer, the patient is asked to do a pregnancy test.

The risk of OHSS

Unfortunately, in IVF, women with PCOS are at a greater risk of a high response to controlled ovarian stimulation and the development of ovarian hyperstimulation syndrome (OHSS). According to Dr Garcia, this is the major risk of IVF in this type of patients – even when using low dosages of hormones. OHSS is divided into three categories: mild, moderate and severe. The symptoms of mild OHSS may include mild abdominal bloating, nausea/vomiting, diarrhoea and enlarged ovaries. Women with moderate OHSS typically have more or less the same symptoms (plus ascites). Mild OHSS also includes laboratory abnormalities such as hypoproteinemia – and that’s why it requires careful monitoring. Women with severe OHSS usually have vomiting and cannot keep down liquids. They experience significant discomfort from swelling of the abdomen and rapid gain weight. They can develop shortness of breath (dyspnea) and blood clots can form in their legs. Patients who experience severe OHSS have to be immediately hospitalised and monitored in intensive care units.

Methods to avoid OHSS

OHSS is a serious condition – but the good news is that its risk can be significantly reduced nowadays. There are different methods to avoid it. Dr. Garcia mentions the use of a different medication to induce ovulation (GnRH agonist instead of Ovitrelle) or the use of Metformin as an adjunct during IVF. There is also another strategy which is cycle segmentation. It means no transfer in the same cycle and going for an elective freeze-all policy (freezing of all the embryos). With the latter, the first frozen embryo can be transferred when there is no risk of OHSS. For women who don’t have a regular cycle (like the most of PCOS patients), additional estrogen and progesterone medications are used to prepare the endometrium and develop it to the right stage before the embryo transfer.

The conclusion

Polycystic ovary syndrome (PCOS) is a multi-faceted condition. That’s why, when choosing an effective treatment option for the woman with PCOS, it is crucial to use a holistic approach. A multi-disciplinary care addresses not only subfertility or anovulation but also metabolic and psychological issues that are often associated with its spectrum.