Is IVF a real solution for infertility caused by Polycystic Ovary Syndrome?
PCOS is a hormonal condition affecting women in reproductive age affecting 1 in 10 women. The exact cause of this condition is unknown but for sure it’s a combination of genetic and environmental factors. Unbalanced hormones levels are also key factors why PCOS leads to fertility issues. In this webinar, dr Marina Soto Sogorb, gynaecologist and obstetrician at Phi Fertility, talks about polycystic ovary syndrome and answers the important question: Can IVF help to overcome infertility caused by PCOS?
According to dr Marina Soto Sogorb, in order to understand polycystic ovary syndrome (PCOS) one has to understand what’s going on in a normal menstrual cycle. Brain structures called the hypothalamus and pituitary gland control the menstrual cycle. Together with the ovaries and the uterus, they follow a sequence every month. The objective of this sequence is to prepare the body for pregnancy. Hypothalamus produces FSH (follicle-stimulating hormone) and LH (luteinizing hormone) while the ovaries produce estrogen and progesterone. These hormones make the lining of the uterus thicker to prepare the body for pregnancy. During the first half of the menstrual cycle, FSH increases. This increase stimulates the ovaries to produce the cord of follicles, among which one stands out of the rest. This is the so-called ‘dominant follicle’. It produces the rising level of estrogen and this, in turn, causes the thickening of the endometrium (the lining of the uterus). The increase of estrogen also causes the release of LH in the pituitary gland. At the moment of LH peak, the ovulation occurs.
The ovulation is the release of an egg from the ovarian follicle. After the ovulation, the next phase of the cycle begins. The follicle, that was left by an egg, starts to produce progesterone. When the fertilisation doesn’t take place, the follicle contracts inside the ovary and the levels of estrogen and progesterone begin to shrink. This causes the endometrium to shed and results in menstruation – and the start of the next menstrual cycle.
After this detailed explanation of the menstrual cycle, dr Marina Soto Sogorb goes on to talk about PCOS ( polycystic ovary syndrome) itself. PCOS is the most common endocrinopathy in women of reproductive age. Its prevalence oscillates among 10%. The causes of PCOS are generally unknown – however, genetic and environmental factors are taken into account.
PCOS syndrome and its symptoms
PCOS is characterised by hormonal imbalance. What we understand by that is higher production of LH (in comparison with FSH) and an increase in androgens. Hormonal imbalance causes ovulatory disfunction, resulting in excessive follicular recruitment: large cohorts of follicles and growth of follicles ceases.
The changes in hormone levels influence women’s health, well-being and physical appearance. One of the symptoms is hyperandrogegism that manifests itself as acne, increase body hair and scalp hair loss, as well as usual overweight. Ovulatory dysfunction, on the other hand, results in absence or irregular menstrual periods and difficulty in getting pregnant. Dr Marina Soto Sogorb admits that the symptoms can be very variable but in many cases the first symptom is infertility a woman.
Dr Marina Soto Sogorb says that women often ask how they can know if they have PCOS. In order to diagnose PCOS, a gynaecologist should conduct an interview to determine a patient’s medical history. The ultrasound scan of ovaries is also needed. The ultrasound description of a polycystic ovary consists of more than 12 follicles with the diameter of 2-9 milimetres. A gynaecologist may request a hormonal determination, too. When the latter shows an increase in LH levels and androgens, it is a sign of PCOS.
However, due to phenotypic heterogeneity, the diagnosis of PCOS is very complex. Medical criteria used by doctors for diagnosis are the following: hyperandrogenism, ovulatory dysfunction (absent or irregular periods) and polycystic ovaries on ultrasound. At least 2 of these 3 criteria have to be met in order to recognise PCOS in a woman. Dr Marina Soto Sogorb says that according to these criteria, we can observe 4 phenotypes: A,B,C and D. The most common is ‘A’ and it arises from the combination of hyperandrogegism, ovulary dysfunction and polycystic ovaries morphology by ultrasound. About 60% of women with PCOS are classified with phenotype ‘A’. The phenotype ‘B’ is a combination of hyperandrogegism and ovulary dysfunction while ‘C’ (called an ‘ovulatory phenotype’) conflates hyperandrogegism and polycystic ovaries morphology. The last phenotype ‘D’, which is also the least common one, combines both ovulary dysfunction and ultrasound criteria.
Dr Marina Soto Sogorb says that there are few options of PCOS treatment. If the problem is overweight, then one of the most effective approaches is weight loss. Manifestations of hyperandrogenism may be treated with contraceptive pills – assuming, of course, that a patient is not planning a pregnancy. Another option here are antiandrogens – a group of medicines that counteract the effects of the male sex hormones.
Combating PCOS and infertility
But what is the solution of infertility problems resulting from PCOS? According to dr Marina Soto Sogorb, the main problem here is anovulation – the failure of ovaries to release an oocyte during a menstrual cycle. Assuming that the only pathological factor is the lack of ovulation, then doctors usually recommend an available reproduction technique as a cure.
The first step of the treatment is clomiphene citrate. It’s an ovulation inductor administered orally that stimulates the ovaries to realise follicles. It’s an easy and economic way of treatment. The results are quite impressive – the ovulation rate is 80% while cumulative gestation rate equals 40% (in 6 cycles). However, the main risk here is multifollicular development and, as a result, a multiple pregnancy.
If a woman doesn’t get pregnant with clomiphene citrate, artificial insemination is the second step. It consists of ovarian stimulation with low does of gonadotropins (either FSH or LH) in subcutaneous injections. After the ovulation occurs, the semen (collected on the day of the insemination) is introduced into the uterine cavity. Dr Marina Soto Sogorb assures that insemination isn’t a painful procedure and it doesn’t need anesthesia. Again, like in case of clomiphene citrate, the main risk is multifollicular development and a multiple pregnancy. The gestation rate here is 15% in one cycle while cumulative pregnancy rate is 30%.
PCOS and IVF
If a woman does not get pregnant by artificial insemination, IVF is the next step. It is the most expensive and also the most complex technique as it consists of several phases. The fist one is the ovarian stimulation with high doses of gonadotropins to achieve the development of multiple follicles. When the follicles achieve an adequate size, the ovarian puncture for oocyte extraction takes place. The puncture is performed in an operating room under general anesthesia. Then the fertilisation of the egg is conducted in a laboratory. Embryonic laboratory development takes about 2-6 days and then the embryo transfer is made. The gestation rate in PCOS patients after IVF is up to 75%. Having said that, dr Marina Soto Sogorb admits that IVF is a real solution to infertility caused by polycystic ovary syndrome.
Questions from the event
I’ve read that there‘s a surgery treatment, am I right?
Yes, there is a surgery treatment that is called ovarian drilling. The procedure is to make little holes in the ovaries with the use of a laser or a needle. But it’s an invasive method and it is indicated only when there is already a laparoscopy necessary for some other reason.
If I have PCOS, will my daughter have it, too?
Like I said, the causes of PCOS are unknown. But genetic and environmental factors may be related here, too. So If you have PCOS, it does not necessarily mean that your daughter is going to have it as well. But she might be at higher risk of having it than other women.
I have read that there was a study showing that women with PCOS seemed to have a higher rate of live births after undergoing IVF with frozen embryos than with fresh embryos. Is it something that has been confirmed and do you agree with it?
As there is a higher risk of hyperstimulation in PCOS patients, it’s better to freeze the embryos. And then in the next cycle we prepare the endometrium and make the embryo transfer. But a higher rate of live births depends on the number of follicles at the time of the ovarian stimulation. If the follicles are ok, then it doesn’t matter if the transfer is done with fresh or frozen embryos.
My doctor prescribed me metformin, is that good?
I didn’t say anything about metformin but PCOS is frequently associated with insulin resistance. Metformin is often used to treat diabetes so it may help with PCOS in these cases of insulin resistance. It may help to improve insulin’s ability to lower blood sugar levels. So it’s good and it’s needed.
Will I have any problems in pregnancy with PCOS?
If you have PCOS and you are pregnant, you can have normal development of your pregnancy. You don’t have to worry about that. But it’s true that in case of PCOS patients, there is a higher risk of miscarriages, gestational diabetes and preeclampsia.
Does it mean that the quality of my eggs is worse because I am producing more eggs during a cycle?
No, the quality of eggs isn’t worse because there is a bigger number of eggs in a cycle. But some studies say that the quality of eggs in PCOS patients is worse. However, it’s not very clear because it depends on the phenotype of PCOS.
I am 43 with PCOS. I have had 2 failed IVFs. My 2nd IVF was very poor quality so there was no transfer. I am currently on metformin (1500mg daily). Will this help with my eggs’ quality? My AMH level is 16. Should I continue to try with my own eggs or should I go for egg donor?
There are two things to consider here: firstly, it’s PCOS and secondly – the age. At 43, we usually recommend an egg donor because of genetic information in the patient’s eggs. If a woman is over 40, unfortunately there are a lot of aneuploidies in her eggs.
Apart from Clomid, are there any other tablets you can suggest? Because I’ve had ovarian cysts in the past.
Clomid or clomiphene citrate is a way of oral treatment. There are other tablets called Letrozole or aromatase inhibitor. They reduce the peripheral conversion of androgens to estrogens, by blocking the enzyme aromatase. Consequently, there is a decrease in estrogen levels and a negative feedback in the pituitary gland, resulting in an increase in gonadotropin releasing hormone. So it seems that Letrozole is useful. But in Spain, the use of Letrozole is not right in all medical techniques. So we can use it for four days.
What tests would indicate to me that I could proceed with donor eggs?I am 36 and I failed last IVF… Maybe the clinic was not good? I had 20 eggs and 5 day 5 embroys.
In order to proceed with donor eggs, we only have to check if your endometrium is okay and that you don’t have any problems in your uterus cavity. We have to have a donor and sperm capable of fertilisation. And then we only have to do the embryo transfer with donor eggs.
Is it true that women with PCOS have levels of AMH hormone 30% higher than normal?
I really don’t know if it’s exactly 30% or more or less. But it’s true that AMH levels in PCOS patients are higher than in other women.
What is the ideal thickness of the endometrium for an embryo transfer?
The ideal thickness is around 9 mm but the appearance of the endometrium is important, too. We like three-laminar endometrium best.
Is there something I can do to lower FSH?I have read that PRP can help but this is still an experimental procedure… Or is it already getting some positive reviews?
I really do not know about any experimental procedures or studies going on. But surely you can’t do anything by yourself.
What should a woman do after a transfer for optimal implantation? Should she be on bed rest for a few days or rather walk around and exercise?
On the day of the transfer, we recommend you to be relaxed and not to do any strong physical exercises. But afterwards you can just lead a normal life.
Can I have PCOS and be unaware of it? I mean I have irregular cycles but no other symptoms. Is it possible that the diagnosis is not correct? Or if it’s diagnosed, is it 100% sure that I have it?
Like we saw during the presentation, there are four different phenotypes of PCOS. In one of them you don’t have hyperandrogenism, in others you have normal cycles, etc. So it depends on the
phenotype. If you have at least two of the three medical criteria, you can be diagnosed with PCOS. So you can have PCOS and irregular cycles but no other symptoms. The symptoms are very variable because the diagnosis is very complex.