Webinar broadcast: youtube.com/gyncare
Presenter: Andrea Hladovcová, MD
gynaecologist and reproductive specialist from the Gyncare centre in Nitra
Polycystic ovary syndrome (PCOS) does not have to be a barrier to getting pregnant with the right treatment. In the webinar, you will learn what you can do yourself for a successful pregnancy and what a reproductive specialist at an assisted reproduction centre can help you with. In any case, the pursuit of a baby with this diagnosis should not be postponed. Find out more and watch the webinar.
What is the cause of polycystic ovary syndrome (PCOS)?
The cause is not yet fully known. In PCOS, there is a disturbance in the production of steroids, resulting in hormonal changes and impaired insulin action. There is an increase in insulin resistance, which occurs in the majority of cases of this syndrome.
Genetic predisposition also plays a role, as do lifestyle and environmental factors. Thus, all this probably has an influence on the development of PCOS.
About half of patients with polycystic ovary syndrome are overweight. With increasing weight, the risk of PCOS increases. Most patients who are overweight also have increased insulin resistance, which causes an increase in blood insulin and hormonal imbalances. Hormonal imbalance causes ovulation disorders up to anovulatory cycles.
How is polycystic ovary syndrome (PCOS) diagnosed?
Every patient who comes to our centre undergoes basic examinations, based on which we look for the cause of infertility.
Hormonal profile
The main point in the basic algorithm of diagnosis is the examination of the hormonal profile, which we examine from the blood. In the hormonal profile, we see various hormonal changes. In polycystic ovary syndrome, we mainly observe increased levels of androgens. In polycystic ovary syndrome, there is a marked predominance of luteinizing hormone (LH) over follicle-stimulating hormone (FSH), which results in insufficient follicle stimulation for ovulation to occur, resulting in an anovulatory cycle or anovulation.
In the hormonal profile, we also see elevated anti-Müllerian hormone (AMH), which is the most important in the case of a diagnosis of PCOS from a hormonal point of view. This is a hormone that is formed in the cells of the tiny follicles, which are multiplied in the case of PCOS. Their number is increased compared to the standard. AMH is an indicator of ovarian reserve and therefore the number of follicles in the ovaries. The advantage of this hormone is that it does not have significant changes within a single menstrual cycle and even between menstrual cycles. Therefore, it is a very useful investigative indicator of ovarian reserve. Of course, with age, AMH gradually decreases as the ovarian reserve also decreases. In the case of PCOS, AMH is significantly elevated as the number of follicles in the ovaries is also increased.
In the case of anovulation, when ovulation is absent, the corpus luteum is also absent. As a consequence of the absence of the corpus luteum, progesterone is also reduced in the later stages of the menstrual cycle, which is also seen in the hormonal profile.
Ultrasound examination with a transvaginal probe
The basic algorithm for the examination of patients in our hospital, but not only for polycystic ovaries, but for every patient at the initial examination, includes ultrasound examination of the ovaries by transvaginal sonography. We monitor the number of antral follicles in which immature eggs are deposited. Their normal number is 5 – 7 on each ovary. In the case of PCOS, we find an increased number of antral follicles.
Another option in the case of PCOS diagnosis is to monitor the growth of the dominant follicle. An egg matures in the dominant follicle and during ovulation this follicle ruptures. In the case of anovulation, the growth of the dominant follicle is absent.
Clinical picture in PCOS
With PCOS, the patient may observe certain characteristic signs on herself:
- The clinical picture is dominated by a disturbed menstrual cycle, which sometimes comes only three or two times a year, or patients have menstrual cycles longer than the norm.
- Ovulation failure to anovulation are the main factors with a negative impact on fertility in PCOS. Ovulation is an essential prerequisite important for fertilization of the egg and subsequent pregnancy of the patient.
- As a result of increased androgens, there is excessive body hair (hirsutism), acne, seborrhea.
PCOS – where is the problem and what are the solutions?
So let’s take a look at where the problem is and what the solution might be for this syndrome.
The course of a normal menstrual cycle with ovulation
Ovulation is the process by which a mature oocyte matures and is released into the fallopian tube. At the onset of menstrual bleeding, there is normally the growth of several follicles, sometimes as many as five or six, one of which continues to grow and becomes the dominant follicle. In such a follicle, the egg gradually matures and due to the influence of the right ratio of hormones, the follicle ruptures, the egg matures and the egg is released into the fallopian tube. From this follicle, which bursts and from which a mature egg is released, the so-called corpus luteum, an endocrine organ that produces progesterone. Its concentration increases gradually under normal circumstances. Progesterone has the task of preparing the lining of the uterus for the embryo to nestle, called. secretory transformation of the endometrium. In the fallopian tube, the fertilisation of a mature egg takes place – the fusion of the egg with the sperm – the resulting embryo passes into the lining of the uterus, where it becomes embedded. The corpus luteum and the progesterone-producing corpus luteum support the maintenance of pregnancy in the uterus, and the pregnancy hormone-producing corpus luteum subsequently maintains the function of the corpus luteum until the placenta is formed, that is, until approximately the eighth week of pregnancy, after which the corpus luteum gradually ceases to exist and the placenta takes over the function.
Story menstrual cycle in PCOS without ovulation
In polycystic ovary syndrome, ovulation is often absent. This means that there is no growth of the dominant follicle, no rupture of the follicle and release of the mature egg, and thus no formation of the corpus luteum. Lack of progesterone is manifested by the fact that there is no transformation of the lining of the uterus. The consequence of this is a long menstrual cycle.
Long menstrual cycles are caused by the absence of progesterone and corpus luteum, because there is no transformation of the uterine lining and as a result, there is an absence of menstrual bleeding. To restore menstrual bleeding, hormonal drugs are used in gynaecological practice, which can be in pill form – for example, Duphaston, Progestanelle or Utrogestan, or progesterone is supplemented in injectable form to induce bleeding, but it does not replace ovulation, which is absent in PCOS. Gestagen supplementation, progesterone supplementation is not going to solve our problem. If the patient is trying to conceive, ovulation needs to be induced and this is the basis for achieving the desired pregnancy. Gestagen or progesterone supplementation makes sense if the patient is not trying to get pregnant but wishes to have regular bleeding.
What can the patient do for herself?
Weight and lifestyle modification
It is important to remember what I said at the beginning – being overweight exacerbates this hormonal disorder, and therefore in patients who have a higher BMI, i.e. are overweight, it is important to modify the lifestyle, increase physical activity and reduce weight. Weight loss reduces insulin resistance, which is the cause of anovulatory cycles. This will also reduce the level of androgens and may lead to spontaneous restoration of ovulation. In the case of weight modification, the sensitivity of the ovaries to the body’s own hormones, such as luteinizing hormone and follicle-stimulating hormone, also increases, as does the sensitivity to drugs that are designed to induce ovulation, and also to drugs that are designed to stimulate the ovaries in the IVF cycle.
Example from practice
A patient with severe polycystic ovary syndrome was able to lose 19 pounds in six months. Before weight adjustment, she had menstrual bleeding 3 times a year, repeated anovulatory cycles. After weight adjustment, menstrual cycles spontaneously appeared every 35 days, she even began to ovulate spontaneously without any support from medication. This means that the sensitivity of the ovaries to her body’s own hormones has increased. She is now in her sixth week of pregnancy. She got pregnant spontaneously, so weight adjustment definitely makes sense. And there are many such examples. This responsible approach can help a large proportion of patients.
Medicamentous treatment
Induction of ovulation can also be achieved in patients by medical treatment. For most patients, we use the well-known clomiphencitrate or Clostilbegyt. These are medicines that are called. antiestrogens, that is, it affects estrogen receptors, and on the basis of hormonal changes and feedback, follicle-stimulating hormone is flushed out of the sub-ovarian gland. That is, there is a flush of the body’s own hormones, which should ensure the growth of the dominant follicle. We have this medicine in pill form and it is designed to stimulate follicle growth. In the case of using Clostilbegyt, the disadvantage is that multiple follicles may also grow. This means that in the case of growth of three or more follicles, we do not recommend planned sexual intercourse or intrauterine insemination, as the risk of multiple gestation is extremely increased. Based on the recommendations of the professional society, clomiphenylacetate should be used in a maximum of 3 cycles and in case of failure it is advisable to visit an assisted reproduction centre already. In rare cases, it may happen that with long-term use of Clostilbegit, the growth of the lining of the uterus is inhibited, and so despite the follicle growing and ovulation being achieved, pregnancy may not occur because the lining may be too low.
Another drug used is Letrozole. Letrozole works very similarly to clomiphenylacetate, but on a different level and does not affect the endometrium. More often, it provides us with the growth of only one follicle. It is also taken in pill form and is also recommended to be used in a maximum of three cycles. In case of failure, it is already advisable to visit an assisted reproduction centre.
Insulin sensitizers are nutritional supplements and medications that improve the response of tissues to insulin, thus reducing circulating insulin levels in the blood and correcting the hormonal balance that is disturbed in PCOS. Insulin sensitisers reduce insulin resistance and improve the ovarian response to stimulant drugs in the IVF cycle, which then allows us to use lower doses of hormones in the IVF cycle, thus reducing the risk of the so-called hyperstimulation syndrome. Insulin sensitizers include vitamin supplements containing inositol, especially myo-inositol and D-chiro-inositol, respectively. Metformin. Metformin is still used off label in Slovakia. That is, this drug is not intended for the treatment of polycystic ovaries, but for the treatment of type 2 diabetes. However, it reduces insulin resistance and overall improves hormonal balance and hormonal balance that is disturbed as a result of PCOS.
If the patient fails to grow a follicle or repeatedly grows more follicles despite Clostilbegyt, Letrozole and insulin sensitizers therapy or lifestyle and weight modification and it is not possible to carry out planned sexual intercourse or insemination, it is already indicated to reach for the cycle of artificial insemination. The same is true for a patient after three cycles of Clostilbegyt or gonadotropin stimulation if pregnancy has not occurred.
We use these drugs in assisted reproduction centres to get more follicles to grow. These are hormonal medications that are injectable in subcutaneous form, i.e. the patient self-administers them subcutaneously at home, either in the lower abdomen, thigh or arm. IVF cycle is indicated, as I said, in case of growth of a larger number of follicles, when there is a high risk of multiple pregnancy.
Ovarian hyperstimulation syndrome in PCOS and its prevention
Ovarian hypestimulation syndrome in PCOS and its prevention
Patients who have polycystic ovary syndrome are at risk for developing ovarian hyperstimulation syndrome. Ovarian hyperstimulation syndrome is a rare but possible complication that is related to stimulation and the IVF cycle. Patients who have a very high ovarian egg reserve, a very high follicular reserve, are at risk because even if lower doses are used, follicular growth is expected to be higher. Therefore, we use various preventive options in these patients to avoid ovarian hyperstimulation syndrome. This therefore includes the use of a certain type of protocol in the IVF cycle. Also, lower doses of hormones and so-called. freeze all, which is the freezing of all embryos obtained. We then wait a certain period of time, most often one menstrual cycle, for the hormones to wash out and the ovaries to calm down, and then we perform a delayed embryo transfer. Because ovarian hyperstimulation syndrome is triggered by pregnancy hormone, we postpone the embryo transfer if there is a risk to reduce the patient’s risk of developing hyperstimulation syndrome as much as possible.
Pregnancy with PCOS
Pregnancy in patients with PCOS is associated with several risks:
- a higher risk of early miscarriage, which is mainly related to obesity,
- in the second and third trimesters of pregnancy, there is a higher incidence of gestational diabetes mellitus (gestational diabetes), high blood pressure or pre-eclampsia.
For this reason, it is very important not only to diagnose polycystic ovary syndrome in preconception before pregnancy, but also to prepare the patient for subsequent pregnancies in order to reduce as much as possible the possible risks resulting from this syndrome.
Questions
Yes, I come across this very often indeed, so the lady doesn’t have to worry about being alone in this. Often patients with severe PCOS and with high insulin resistance taking metformin complain of indigestion in terms of stomach pain, abdominal pain, diarrhea and so on. It should be taken into account that you must not take this medicine fasting. I also recommend limiting sweets, because even then difficulties tend to appear. The effect of this medication will reduce insulin resistance and weight, so despite the digestive upset, I would recommend continuing to take it.
For significant difficulties, nutritional supplements that contain inositol, such as Inofolic Combi, can be tried and may also help in the case of increased insulin resistance. I don’t know what the weight is, what the BMI index is. If there is also a modified lifestyle, adjusted weight, then there is the possibility to reach for medical treatment, either with Clostilbegyt or Letrozole in the outpatient clinic, or visit the centre.
Good question, but I’d also like to talk to this patient because I don’t see everything. I don’t see the weight again. I don’t think gluten and lactose affect ovulation. But perhaps the patient was slightly overweight, which she corrected by restricting gluten and lactose, which may have had a beneficial effect on menstruation and ovulation. So I rather think it’s going to be somewhere in this.
I don’t know if you’ve been pregnant before and you’ve miscarried repeatedly, but you definitely need to do other tests, not only hormone profile and histamine intolerance, but also to investigate thrombophilic mutations, blood clotting, because that can be the cause of repeated miscarriages. Also genetic testing of the couple. I think you probably have an endocrinological test done, immunological probably also, when you write histamine intolerance. So, we should also investigate the haematological and genetic side and in case of pregnancy, blood thinners can be administered after the haematological examination, also preventive gestagens can be administered. As I mentioned, progesterone, Progestanelle, Utorgestan, Duphaston – drugs that support the function of the corpus luteum.
No, most of the time PCOS does not get worse with age. The ovarian reserve decreases by natural attrition. The condition of PCOS can worsen if the patient does not adjust her lifestyle, she gains weight, menstruation is then less frequent, follicles are more, etc.
In the case of PCOS, what is important is not that the ovaries look physiological, but that we achieve ovulation. So, by adjusting the lifestyle, it is possible to induce a hormonal balance that will result in spontaneous ovulation, and thus a spontaneous pregnancy can be achieved. So yes, by adjusting your lifestyle you can help yourself to pregnancy. I have encountered this case many times.
How long does it take to treat polycystic ovaries?
We can’t cure polycystic ovaries, there is no pill that you take and you are cured. The treatment may last, for example, 1 month when the only problem is that the patient is not ovulating. We put on medication, induce ovulation, and if she has patent fallopian tubes and the partner has no problem with the spermogram, she can get pregnant that first month.
However, there are patients who want to adjust their weight first, adjust their lifestyle, and that can take half a year, three quarters of a year. We then put on medication to induce ovulation, if the ovaries don’t respond to this medication then we continue with an IVF cycle that lasts about 3 weeks until we do the embryo transfer. So it’s individual. It really can be different for every patient.
Is it possible to get pregnant without problems even with PCOS?
If in the case of PCOS, ovulation is present, it is possible to conceive without problems.
Certainly, if the only problem is the absence of ovulation and the fallopian tubes are patent, if we can achieve ovulation and the growth of a dominant follicle with medication, then in this case there is indeed a chance to conceive even with insemination.
Vitamin C does not. As far as contraception is concerned, the menses was regular, that is, the bleeding occurred regularly, always after the contraceptive was discontinued, because with contraception there is no ovulation and the bleeding occurs as a result of a drop in hormones, so it was hormone-induced menstrual bleeding, but not ovulation. Of course, that’s the point of contraception. Not every patient has to have an elevated BMI, meaning about 50% of patients are overweight, but not all of them have to be. So being overweight is not a 100% sign in case of PCOS. She was taking Duphaston, yes, there was bleeding with Duphaston, that’s normal. That’s what I said in the lecture. She was supplementing with gestagen in the second half of the cycle and as a result of the drop in gestagen there was bleeding, she discontinued it, so I assume there was no menses again after discontinuing Duphaston, though she says she gradually lost menses, Clostilbegyt twice unsuccessfully. I don’t know what failure means, if it was able to achieve follicle growth but didn’t conceive, or failure means it failed to achieve growth in any follicle. So, there is a difference in this, and if no follicle has grown, it is certainly advisable to visit an assisted reproduction center. If the follicle growth has been achieved, it is possible to try again and if it is not possible to get pregnant, then according to the guidelines it is already recommended to visit an assisted reproduction centre.
The sooner you start dealing with diagnosis and subsequent treatment, the better your chances of pregnancy. Of course, after 35. year of life, the ovarian reserve begins to decline, the quality of eggs begins to decline. There is still plenty of time before that age, but you also need to think that there may be other associated problems, so I wouldn’t leave it to the last minute and maybe visit an assisted reproductive centre or gynaecologist. Just for that basic diagnosis, so that based on the results we know how much time you still have or when it would be best to start dealing with the pregnancy.
Can the corpus luteum rupture even if ovulation is ongoing?
The corpus luteum does not rupture, the dominant follicle ruptures and the egg is released from it and the ruptured dominant follicle then gives rise to the corpus luteum. It may be that there is growth of a dominant follicle and it doesn’t rupture and the egg is not released and that follicle may continue to grow and that may delay menstrual bleeding or as an incidental finding in an outpatient gynaecologist we may see a cyst, or a larger follicle, but then gradually when menstruation comes it will be absorbed or rupture and then a new menstrual cycle will start so that the dominant follicle may not rupture. Occasionally, this happens even in patients who have hormones completely in balance.
I assume that when the transfers were done, the patient was definitely taking some blood thinners, some aspirin or clexane, some gestagen to support the pregnancy. I’m sure there were some hormonal medications to maintain the pregnancy, so what else to do next? One option is indeed to examine the embryos genetically, since the most common cause of first trimester miscarriages is either a genetic defect in the embryo or an increased clotting of the woman’s blood. So I don’t know if thrombophilic mutations are investigated, which I’ve been told are a possible cause of recurrent miscarriages. That will certainly give us an answer or move us further along in our investigation. And as for some medicine, in order to adjust the weight a little, it would be best to adjust the lifestyle, increase physical activity.
Inofolic is definitely good. It’s a nutritional supplement that can help, but it’s not a cure, of course. In about 20% of patients, Inofolic does not work. They may be resistant to it. So even if a patient is ovulating regularly, it does not necessarily mean that she will get pregnant right away. Since menstruation is regular, I assume that ovulation will also be present. Inofolic as a dietary supplement is suitable, you can continue to take it during treatment. Weight gain after discontinuation of contraception can be caused by the so-called. antiandrogenic and antimineralocorticoid effects of contraception itself. This is the effect thanks to which patients do not retain water in the body. This means that after discontinuation of contraception, this effect will decrease and weight gain may occur.
If you have regular periods and you ovulate regularly, even if the cycles are longer, they can be 40- to 50-day cycles, but they are regular and ovulation is later, I don’t see any reason at the moment why you should from the beginning or from the 16th. of the day to take Progestanelle for those 10 days. Because if you ovulate and develop a corpus luteum, progesterone should be enough to get pregnant. In case your period is late or you take a pregnancy test and it’s positive, then it makes sense to put Progestanelle on, because if you start taking it on the 16th. day and ovulation occurs, for example, only on the twenty-eighth day, the mucous membrane will be too early under the influence of progesterone and too soon it will begin to transform. So maybe either push the Progestanelle, or I would handle it by not giving any and only putting it on from a positive pregnancy test.
Not every patient with a regular menstrual cycle needs to ovulate regularly. But in this case, when menstruation is regular every 28, 30, 35 days, it is assumed that ovulation is also regular, but it can not be proven otherwise than by hormonal profile or ultrasound examination. That said, this way I can’t tell you if you’re ovulating regularly or not, but with a regular cycle the assumption is that you are.
Can Duphaston negatively affect ovulation?
Duphaston does not affect ovulation. It replaces progesterone, which is supposed to make the corpus luteum. If the corpus luteum is absent or absent as a result of anovulation, Duphaston is put on instead of endogenous progesterone from the corpus luteum, which replaces progesterone, does not replace ovulation, and bleeding occurs after discontinuation of Duphaston. So if the problem is that ovulation is lacking, Duphaston does not solve the problem and has no effect on that ovulation.
Can it happen that ovulation takes place, but progesterone is low after ovulation?
Yes, this is called so-called corpus luteum insufficiency, and in that case, for example, frequent biochemical pregnancies can occur. This means that the patient has a positive pregnancy test but eventually fails to keep the fetus, or has a positive HCG, the pregnancy hormone, but this subsequently drops. It may be an indication that that yellow body is deficient, progesterone is low, and that’s indicated for supplementation of progesterone in pill form, either vaginally or orally, or in subcutaneous form in the form of injections.
As for taking aspirin, it should be recommended to you by a haematologist who has probably indicated it. Definitely don’t take it on its own as it thins the blood, it can also cause side effects so don’t put it on yourself. When should I switch to Fraxiparine? Also a question to the hematologist. It works on a slightly different level than aspirin. As for the other question, I don’t see anywhere how old you are, but if it’s not a long time you’ve been trying, feel free to try the natural way. But if, despite years of trying, pregnancy does not occur, it is necessary to seek a specialist in reproductive medicine.
Rather, I think it only affected menstruation, but I can’t rule out ovulation in this case. Well, based on the fact that when you weren’t taking any Duphaston, your periods were irregular, and now all of a sudden you’re having them regularly, I guess it’s probably just because of the Duphaston that the bleeding is occurring. It doesn’t solve the problem of missing ovulation.
After the thirty-fifth year, the options also decrease for patients who have PCOS, because despite the increased number of eggs in the ovaries, the quality of oocytes decreases in every patient. So even in those with a higher follicle count.
Stress is a universal factor that can cause such hormonal changes that can affect both ovulation and the menstrual cycle. So if your periods are absent or irregular, you should definitely have your hormone profile checked, including other hormones such as prolactin.
I know patients are taking it. But I meet patients in the centre who do not have regular menstruation, do not have regular ovulation and who have not been helped by the herbs. It may also be that we tend to concentrate patients whose problem persists, and those patients who have been helped may no longer visit the centre. So for me as a supplement okay. If that doesn’t help, then definitely reach for other medications.
If your gynaecologist has recommended laparoscopy to examine the patency of the fallopian tubes, you can have this examination when you come to the centre, we will have already examined the patency. If there is some other problem, some tumor on the ovary or some endometriosis, and your gynecologist has seen fit to send you for laparoscopy, then it is certainly appropriate to have that. However, I do not have further information on this, so I do not want to make a definite statement.
