In this webinar, Dr Alejandra Aguilar Crespo, Gynaecologist at Equipo Juana Crespo, Valencia, Spain, discussed hormones and their role in fertility. Dr Aguilar has talked about PCOS, hyperprolactinaemia, congenital adrenal hyperplasia (CAH), thyroid disorders and how they can impact fertility.
It’s important to understand that when doctors face a couple with a history of infertility, there are several factors that they have to take into account. It’s known that the age of the woman is one of the most important factors that affect the results of the cycle, but there are indeed other factors that play a vital role in the treatment and cannot be forgotten because these are the hormonal factors.
The endocrine system is very important for the regulation of pregnancy. It’s also essential to understand that the ovulation is precisely regulated by hormones, and any imbalance of this can provoke infertility or alterations during the menstrual cycle.
According to Dr Crespo, when they study an infertile couple the first thing that they have to do in the initial consultation is to evaluate the basal hormones because if there’s any alteration, it’s mandatory to treat it to improve the results. Therefore, the doctor asks about the basal hormone and studies several hormones in the different axes that people have.
Dr Crespo first focuses on the woman’s infertility. It’s important to understand which are the axes. The doctor asks for the ovary and hypothalamus axis, which is the FSH, LH, Estradiol, Progesterone and Anti-Mullerian Hormone. She also asks for Prolactin, Thyroid Hormones, Insulin, Androgens, and vitamin D.
Some hormonal disorders can provoke infertility.
This is the first and most frequent hormonal disorder, which is defined by a hormonal imbalance, and it’s a multifactorial entity that can affect 10% of women of reproductive age.
It’s a metabolic disorder in which the woman generates a high level of androgens, and there’s also an excess of LH release. This causes an inversion of the FSH and LH radio.
The diagnosis is performed by the Rotterdam Criteria, and the woman has to have two of the following three conditions:
It’s very important to treat a woman with PCOS because she’s at risk of the following:
One of the main characteristics of women with PCOS is that they’re at risk of anovulation or oligoanovulation. Dr Crespo mentions amenorrhea, which is the lack of periods or irregular periods that can lead to an infertility problem; therefore, these women often consult with a reproductive clinic.
The first step of the obesity treatment is weight reduction.
If a woman has anovulation or oligovulation, and looking for a pregnancy, it’s important to look forward to an assisted reproductive technique.
If a woman doesn’t want to get pregnant, the best treatment is the contraceptive pill or the progestin.
If there’s an insulin resistance, there’s a treatment called Metformin. This is used for diabetic people, but in patients with PCOS, it affects them in the following way:
Therefore, if a woman has obesity and insulin resistance, it’s important to use the Metformin drug only if it’s prescribed by a doctor.
Hyperprolactinaemia is an excess of production and circulation of Prolactin. This hormone is secreted by the pituitary gland and prepares the breast for milk production. It’s very important to mention that 1/3 of women with amenorrhea, meaning an absence of periods, have hyperprolactinaemia. Therefore, women with amenorrhea have to rule out a possible hyperprolactinaemia.
If a woman has amenorrhea or hyperprolactinaemia, it’s important to exclude some causes of the increase in prolactin, for example:
The symptoms of hyperprolactinaemia are the following:
The diagnosis is made by a determination of the prolactin in a blood test. This hormone should be below 25 nanograms per decilitre.
The treatment for prolactinoma, meaning the pituitary tumours, are:
This pathology isn’t very common, but it’s a hormonal disorder. The Congenital Adrenal Hyperplasia is caused by the enzyme deficiencies, and the most frequent one is the 21 α-hydroxylase.
The 21 α-hydroxylase is a hereditary disease and is produced by the deficit of the biosynthesis of cortisol, which is a hormone, and it increases the ACTH. It also provokes an adrenal hyperplasia (it will be bigger).
The ACTH hormone stimulates adrenal androgen secretion, which inhibits the Gonadotropin secretion and, therefore, can cause infertility, virilization, and menstrual irregularities because the androgen increases.
For the diagnosis, the doctor only does a blood test. Here they will see the following:
The treatment it’s very simple because it’s only the use of Corticoids. Even though the prevalence, according to Dr Crespo, is very small because it’s a hereditary disease, its treatment is important because it restores the menstrual cycle as well as the fertility.
Dr Crespo mentions that it should be taken into account that Hypo and Hyperthyroidism can cause menstrual irregularities and, therefore, decrease fertility. It’s very important to know this because if there’s no treatment, even if a woman has hypo or hyperthyroidism, it has been associated with an increase in maternal and fetal morbidity and mortality.
On one hand, hypothyroidism can provoke:
It’s crucial to treat it with Thyroxine. The ideal TSH level for the pregnancy is below 2.5.
On the other hand, hyperthyroidism can provoke:
For the treatment, Dr. Crespo mentions the two following:
This hormone is getting more and more important in IVF because Vitamin D is responsible for the intestinal absorption of calcium, magnesium, phosphate, zinc, and iron. Its deficiency is related to several diseases, such as:
Vitamin D also has a role in reproduction because it has been demonstrated that:
During pregnancy, Vitamin D enables implantation and stimulates antimicrobial activity. In addition to this, if there’s deficiency it can be related to recurrent miscarriage, preeclampsia, Gestational Diabetes, and metabolic syndrome.
According to Dr Crespo’s words, there are insufficient studies that indicate that vitamin D supplementation significantly benefits the results; nevertheless, some reports argue that it can improve weight, height, and hyperbilirubinemia in pregnant women with gestational diabetes and vitamin D deficiency.
However, the dose mustn’t be over 4000 units. So, vitamin D supplements will only be given if there’s a deficiency, if not, there’s no benefit.
Moreover, Dr Crespo talks a little bit about the Low Ovarian Reserve in women. She mentions that if she asks for a basal hormone and the woman has a low AMH and high FSH, it’s important to understand that she’s probably facing a low ovarian reserve or premature ovarian failure. For this reason, it’s important to advise this woman to look for an assisted reproductive technique or to preserve their fertility.
Normally, the low ovarian reserve is related to age; the older the woman is, the lower the amount of eggs she has. However, in younger women, it’s essential to check:
The doctor needs to see if the woman has a high FSH so that they can treat them because they’ll probably face a low ovarian reserve.
Dr Crespo further explains another pathology related to Chronic Stress. This stress, not the acute one, provokes a high amylase and cortisol level, which is demonstrated to alter the ovulation and seminal quality. Therefore, it also causes infertility.
Dr Crespo further explains another pathology related to Chronic Stress. This stress, not the acute one, provokes a high amylase and cortisol level, which is demonstrated to alter the ovulation and seminal quality. Therefore, it also causes infertility.
Most women who face stories of infertility suffer from stress, and as stated by Dr Crespo, 80 of her patients suffer from stress. Due to this, it’s essential to support them, to offer them yoga and medication, and to help them decrease this stress because it can add an extra disease to the problem.
Another disorder explained by Dr Crespo is BMI. It’s crucial to start a treatment or to start looking for a pregnancy having a correct BMI. Some BMI disorders can lead to amenorrhea and infertility and provoke hypogonadotropic hypogonadism. These are:
Because of this, it’s very important to regulate the BMI. It’s also crucial that, during the first consultation, the basal hormones are considered. If there’s something wrong, the doctor will try to treat it to increase the probability of pregnancy.
If it’s below 20, that’s fine, it’s perfectly done with the Cabergoline, so don’t worry. For the best level, there’s no standard level; the correct level is if you have normal periods with the Cabergoline and with this level of prolactin. If you have restored your menses, everything is fine.
That’s a good level but, of course, just only one determination should be put in context. We should take into account the testosterone level, the DHEA level, the estrogen level, and the progesterone level. However, this level is okay. A low testosterone doesn’t mean a lot of things, it’ll be worse, a high level of testosterone because it can provoke anovulation.
Normally, severe itching can be provoked by an excess of androgen level. This is sometimes called Acanthosis nigricans, which is an accumulation in the skin of androgens. It can be itching but, as far as I know, sometimes the severe itching can be caused by an excess of vitamins; excess in folic acid and vitamin D can provoke hypervitaminosis and cause itching. I don’t know if that’s your case, but I would like to ask for a hormonal blood test.
This level it’s okay, it’s perfectly okay. It’s important not to only take one value but the whole context. If your DHEA is 3200, but your estradiol is very low, it means we have an excessive androgen. But if your estradiol is at the correct level, it means that everything is fine. It’s also important to check for the context, if you have Polycystic Ovarian Syndrome, it’s better to regulate the androgen level.
However, if you have correct menses, you’re not obese, and you have regular periods everything will be fine. We don’t have to be very crazy about which is the best level of hormones. Every patient is different, every person is different but, of course, the DHEA is only asked if we suspect Polycystic Ovarian Syndrome, we don’t ask for routine basal hormones. We also prefer testosterone to the DHEA because the DHEA sometimes can be, even in the same week, very irregular. This level is fine. If it’s more than 5000 we will probably use the contraceptive pill just to decrease this level and to restart a fertility treatment.
It has been demonstrated that sometimes the treatment with FSH, hMG, and high levels of estrogen can disturb the levels of TSH. You have to take into account that the TSH receptor is very similar to the FSH receptors, so sometimes if we have a hormonal imbalance during IVF, the TSH can be very variable. So yes, it can be normal and if it’s 20, of course, after the IVF treatment, before the embryo transfer, you should be regulated to avoid a potential neurocognitive problem in the fetus.
This level of TSH is completely normal as well as T4, so don’t worry. As far as this is below 2.4 and 0.68 is the correct level, you don’t need any medication. Moreover, it has been demonstrated that low TSH, which is not your case, can sometimes provoke menstrual irregularities, but it’s not related to implantation failure and miscarriages. The only problem with hypothyroidism and hyperthyroidism is that it can provoke neurocognitive disorders in the fetus, it cannot provoke a miscarriage.
This is very important to take into account. So, if we see that there is a miscarriage of course everything as well as the hormones should be taken into account, but this is not a frequent cause of miscarriage. The pituitary disease is a multifactorial entity, but it really can provoke a low TSH, low prolactin, low FSH and LH levels, so I don’t think it would be that case. If there’s a miscarriage you have all the more important things such as the embryo, the thrombophilia, the uterus, and the fallopian tubes, more than the TSH levels. Here for IVF, the most important thyroid hormone that we have to take into account is the TSH. If the TSH is okay, we don’t need to ask for the T3 or t4. We’re sometimes over-treating people without the risk.
If you have been diagnosed with Hashimoto’s disease, you’re putting at risk the pregnancy. So, the best treatment, as you’re taking, is levothyroxine, which is the most important thing. If you want to increase your implantation chances, we have to take into account the embryo (if it’s a normal embryo or chromosomal normal embryo), the quality, the uterus, check the fallopian tubes if they’re okay, and if there’s any pathology. So, several factors affect the implantation.
The TSH levels are not a factor, it might affect a little bit, of course, if there’s severe hypothyroidism or severe hyperthyroidism, but if you are already in treatment, don’t worry because it won’t be your case. It’s more important to check the uterus, the implantation area, the endometrial cavity, and also the fallopian tubes. The embryo transfer needs to be performed correctly and perfectly. So, this is the most important factor for implantation.
The pregnant woman who will benefit from the best vitamin D generator is the sun. So, if we sunbathe a little bit, half an hour a day, of course, considering the country you are in, this is the best source of vitamin D. Some foods such as milk, cheese, and also green vegetables can offer a good proportion of vitamin D.
I think it will be better to ask for the midwife, probably, I don’t know which quantity of food you need per day, but, I mean, a normal diet, a completely normal diet with vegetables. A complete and correct diet will be okay, so you don’t need to do a strictly specific diet. Of course, you have to avoid roast meat and fish (it has to be cooked), so there’s no specific food that is better to take.
If your vitamin D level is correct and take it from the sun, it’s okay. If you suffer from a deficiency or insufficiency, it is better to have a vitamin D supply because the dose is high. So, if you have it below 20, it’s better to try to take vitamin D, the cholecalciferol, which is the precursor of vitamin D, it’s better to take that because the dose is higher, and you will restore your vitamin D quicker.
I will recommend it because if your AMH is 0.5 if you have a low ovarian reserve, it means that your androgen levels will be lower. After all, sometimes the androgen levels increase in Polycystic Ovarian Syndrome with people who have a lot of follicles and, therefore, an AMH higher.
Probably, if you’re not facing adrenal hyperplasia, I will recommend you to supplement with DHEA because it has been demonstrated that a testosterone supplement can activate the dormant follicles and, therefore, can increase the number of follicles for women with a low ovarian reserve. So, in that case, you can benefit from taking the DHEA.
There are controversial studies. For example, in our clinic, we used to recommend it, we used to give a vitamin complex which contains melatonin as well because the melatonin relaxes. So, it benefits sleep and when we’re sleeping and when we’re relaxed, the body restores, the brain relaxes and the brain can rest and, therefore, we will feel better and the quality of the egg can increase. In that case, yes, it would and of course, it won’t harm you.
This level depends on if it was a basal glucose or if it was after a glucose ingest, so it depends. It’s not extremely high, 94 is not extremely high, I think it’s a normal level but if it’s only a simple determination probably you have to repeat it in a couple of weeks. If it’s still high, we can recommend the Metformin which can restore the glucose level but only if it’s in a context of infertility or overweight.
Depending on the levels, if your FSH is high, it means that the ovarian reserve is very low, but it doesn’t mean that you’re not going to ovulate. If you have a period of amenorrhoea, it means that your ovulation will be very irregular. So, sometimes, you won’t have an LH surge, but if you have had a period, it means that 14 or 17 days before there was an LH surge. Of course, we can monitor with an ultrasound scan, or you can monitor with an LH stick.
If this is high, it depends, if your FSH is over 50, it means your ovaries are premenopausal, so probably you won’t have periods in a period, but if it’s a high FSH is between 10 and 20, it means that your ovarian reserve is decreasing, but it doesn’t mean that you won’t have regular periods.
The Sexual Hormone Binding Globulin is a hormone that is used to being the androgens and prolactin. For example, it’s like a carrier, when there are prolactin actions, it’s through the Sexual Hormone Binding Globulin. When prolactin is fixed to this hormone, it can do its action. If the producing drops, the hormone drops because this is close to the prolactin, it’s attached to the prolactin. So, it’s completely normal if the prolactin level decreases and the SHBG decrease as well. This determination, it’s not very important for an IVF, only in the context of PCOS.
The Fallopian tubes serve for the In vitro fertilization and for the spontaneous, natural conception. If there is no fallopian tube, we cannot conceive. It is mandatory to perform an In vitro fertilization and do an embryo transfer to put this embryo inside the uterus. It’s one of the best prognoses on the tubal factor.
No. If you’re taking iron, and you’re already taking it and your iron levels are okay, it cannot affect your hormone levels, so don’t worry. Iron is very important, and it’s more important during pregnancy because the requirements of iron will increase and, therefore, the haemoglobin can decrease. The higher deficiency is not related to infertility and implantation failure. Of course, if there is severe anaemia people will feel very, very tired, and there is not an optimum atmosphere to get pregnant, we have to restore everything, but iron deficiency has not been related to infertility.
I’m not very familiar with AChR genesis. That’s an interesting question, I will talk to my colleagues, as far as I know, thyroxine doesn’t imply embryonic myogenesis. I don’t want to give you a wrong answer, but it has been demonstrated that thyroxine is very important to restore thyroid levels, the TSH levels, and it’s also important if there’s a correct TSH level because during pregnancy, this level can increase and, sometimes, when we’re in risk of hypothyroidism, it can affect the fetus. I don’t know if there are studies with thyroid syndrome regarding embryos. It’s interesting, and I will search.
I hope everything is fine, and I wish you all the best and good luck. This will be too soon. If you had your collection yesterday, probably now your hormone, your progesterone level, will be very high because you have ovulated, and also your estradiol level will be very high. So, it’s important, if you want to check your hormone levels, to wait at least your first period after the collection. The hormones will be the estradiol, the progesterone in the luteal phase, and the Anti-Müllerian Hormone, and, if you want to check it, your androgen levels. The most important ones are estradiol, FSH, T4, AMH, and prolactin.
It depends on which hormones. Everybody must understand that if you want to take any vitamin supplement or any treatment, it’s important to understand why you are taking it. We have to take, only if there’s any alteration. If you have hyperprolactinemia or high prolactin, you have to treat it. If you have vitamin D deficiency, you have to treat it.
If you have TSH alteration, you have to restore it. So, if you only take medication to try to increase the chances of a pregnancy, that’s not the point. Sometimes, if you take a lot of vitamins or a lot of supplements, it can be worse, and you can damage yourself. If you want to check how you are during the first consultation, it’s important to ask for a basal hormone. If these hormones are okay, it means that everything is fine, and probably, we only take vitamin supplements, but only folic acid, melatonin if that’s the case, and all the vitamins that can increase the oocyte quality. However, the TSH level, the prolactin, and these important hormones, if they’re okay, you don’t have to take any medication for that.
It has been demonstrated that maintaining the progesterone over 12 weeks is not necessary. It has been demonstrated that progesterone is needed, once we see a heartbeat, we can stop. However, we prefer to maintain it until week 12 just to be completely sure that the corpus luteum or the placenta gives the appropriate level of progesterone. If you want to take it, you can, it won’t be damaged, but it’s not necessary to have a progesterone supplement over 12 weeks.
Unfortunately, the AMH level drops within a year, and after the age of 38, every six months, we can have a drastic drop. You don’t have to be scared, I prefer to check the Antral Follicle Count better than the Anti-Müllerian Hormone because sometimes we have people with a very low AMH, and then we do a correct stimulation, and we can have more eggs than expected. So, we will never discard the patient just by taking into account her AMH, but yes, it can drop within a year. From 30 to 35 years old, this drop, it’s not very significant, but after the age of 37, this drop can be dramatic, even in 6 months, it can drop a lot. Don’t be scared if your AMH is low, it means that your ovarian reserve is low, but if we do a correct stimulation, if we perform an IVF, and we get at least 2 beautiful embryos, your probability of having a baby is high.
It can be the cause, but we have to take into account that sometimes, the hormonal imbalance is in the context of a lot of things. It’s not only the main cause, sometimes we have PCOS and, therefore, we have a hormone imbalance. In repeated implantation failures, there are some tools, and we have some causes that it’s mandatory to check before a hormonal imbalance. It’s important to check the hormones, but for implantation failure, 75% of the cause is because of the embryo.
If the embryo is not of good quality, a chromosomally abnormal embryo, this will be the cause of no implantation. So, you have to take into account the embryo, the uterus, the uterus edges, and the ageing of the uterus. It’s not the same as a 42-year-old uterus than a 30-year-old uterus. It’s important to check the uterus, the implantation area, the endometrial cavity, the endometrium, the thickness, and the appearance of the endometrium, the thrombophilia (it’s important to rule out any possible thrombophilia, and any immune causes of implantation failure). Once we have ruled out all these kinds of things, it’s important to check all the other factors, such as hormones, but you have to check everything in common, not only the hormone imbalance. So, in your case, if you have repeated implantation failures, it’s important to go step by step and to focus on the main areas, in the main causes of implantation failures.
It depends because we have a lot of strategies. For example, in our clinic, I cannot tell you because our treatments are personalized. We do strictly personalized treatment, so it depends, if the woman has a low ovarian reserve, we will focus on a type of stimulation. If there’s a polycystic ovary, it’s very important to stimulate correctly the polycystic ovary because as they have a lot of follicles, it’s important to make a balance. If we use very slow doses of hormones, we will have a poor response, and we will have a bad result, on the contrary, if we have very high doses of hormones, probably we will have hyperstimulation syndrome, and the oocyte will be in a bad quality.
So, it’s important to have a balance. It’s different to stimulate the polycystic ovary than a low ovarian reserve. It’s different to stimulate a tubal factor than an older woman, so I cannot tell you what is the stimulation strategy because it depends on the characteristics of the patient, the ovarian reserve, the age, and the results of the previous cycles. Every patient is different.
