In this webinar, Dr Anna Voskuilen González, a Specialist in Obstetrics, Gynaecology and Reproductive Medicine at Reproclinic, (Fertty International), Barcelona, Spain, will explain how ovulation works, and all there is to know about your fertility when you’re trying to conceive.
Women are born with a certain ovarian reserve, which decreases with age. This decrease is more important after the age of 35-37, and it is also related to a decrease in terms of oocyte quality. We can test the ovarian reserve, but we cannot test the egg quality. After 40 years old, there’s difficulty in getting pregnant, there is a higher rate of miscarriages and more abnormalities in embryos, this again is related to age.
What kinds of ovarian reserve tests do we have? There is FSH (Follicle-stimulating hormone), Estradiol AMH (Anti-Müllerian hormone) and AFC (Antral follicle count). An elevated FSH indicates diminished ovarian reserve. AMH is produced by pre-enteral and small antral follicles. It can be tested at any moment of the cycle, it gives an idea of the total amount of ovarian reserve you have. AFC is checked by ultrasound, at the beginning of the cycle, different follicles can grow in response to the hormones, and the follicles can be seen on the ultrasound because they have a bit of liquid, which also allows the doctors to see what number of follicles you have.
There’s the hypothalamic pituitary ovarian axis, so the menstrual cycle is regulated by the central nervous system (CNS). The first level will be the hypothalamus which produces GnRH pulses, which stands for Gonadotropin-releasing hormone, it will vary in frequency and amplitude and will stimulate the anterior pituitary gland to produce gonadotropins, which are the FSH and LH. FSH (Follicle stimulating hormone) and LH (luteinizing hormone) are going to stimulate the ovaries, and the ovaries are going to produce several hormones that will also have an impact on the other phases of the cycle.
Some external stimuli could affect the hypothalamus and could change this axis, including stress, lack of sleep, sudden weight loss or excessive exercise). This could create irregularity in your menses.
Cycles that last 21 or 35 days usually are thought to be ovulatory. Different follicles are available and can grow. Not all follicles grow, the dominant follicle is selected, and others are lost. This dominant follicle grows in response to FSH and LH and produces oestrogens, which in turn will cause the growth of the endometrial lining during the proliferative phase. Follicle growth produces estrogen that progressively increases, LH peak occurs, and after approximately 36 hours, ovulation takes place.
If you have sexual intercourse, the spermatozoids will swim up to the tube, and if there’s fertilization, the embryo will be produced in the tube and then will travel to the uterine cavity, where it will implant in the endometrium.
What happens after ovulation apart from that? After the ovulation, the progesterone is going to rise and it will be also responsible for changing the endometrium so that it can receive the embryo and let the embryo implant.
Ideally, it’s best to have sexual intercourse as close to ovulation as possible, but, indeed, it’s not easy to exactly know when you’re ovulating. Ovulation takes place approximately 14 days before your period. The egg has the possibility of surviving for 12 or 24 hours, and sperm can survive between 2 and 5 days in the female genital tract. Therefore, it is recommended to start intercourse at least 4 or 5 days before the middle of the cycle. That allows the sperm to ‘wait’ for the egg. Signs of ovulation include:
After ovulation, the body temperature will increase because the corpus luteum produces progesterone, and this stimulates the central nervous system to increase the body temperature. Progesterone levels can also be tested in the mid-luteal phase, which is 7 days after ovulation, to see if it’s positive or not, meaning if you have ovulated or not.
Another option is also to test LH level to see if LH surge can be detected in urine, those tests must be done 4 or 5 days before the middle of the cycle, ideally, it could be done every 12 hours to avoid missing shorter peaks. Keep in mind that sometimes there might be false negatives because of short peaks. There could also be false positives, which means that you have a positive test that you are not ovulating. This can happen if you are suffering from PCOS (Polycystic Ovary Syndrome) with elevated LH levels from the beginning of the cycle, menopause, or premature ovarian failure where the LH will increase and will give a false positive test, so it’s better to test with these urine tests and see the estrogen levels and the LH levels because it’s possible to detect the estrogen peak and LH, which means that you are going to ovulate.
In general, try to carry out a lifestyle as healthy as possible, including a varied diet, fresh, unprocessed food, avoiding toxins and a sedentary lifestyle, a moderate physical exercise. If you have any medical conditions or any medical problems, contact your doctor to be sure that you are in the best condition to try to conceive when the treatment begins. If you need any change in the medication because it could interfere or be harmful, do it before. Other types of treatments have been postulated as possible aids for quality improvement, like melatonin and Coq10, but remember, there is still no strong consistent scientific evidence to say that it helps and can make big changes in egg quality or possibilities of achieving a pregnancy. There are no differences in positions during sexual intercourse nor in staying in the supine position after.
A varied and equilibrated diet can have a positive impact on your health and also on your egg quality. Your diet should include complex carbohydrates, omega fatty acids, fresh vegetables and fruits, nuts, cereals, blue fish, and meat, it’s best if all of those are organic. It’s important to look at the folic acid level, vitamins B6 and B12. You should avoid processed foods, saturated fats, sugary drinks and so on. Supplementing folic acid should start before trying to conceive. Folic acid is very important for the nervous system formation and the closure of the neural tube, which happens early during pregnancy. It’s important to have these levels corrected before you know you are pregnant. Folic acid can be found in green leafy vegetables, citrus fruits, legumes, liver, seafood, and blue fish but more in vegetables than in foods of animal origin. It’s better to steam or eat crude or raw than cook or freeze the vegetables because the amount of folic acid can decrease. It’s also important to start a preconception multivitamin or a folic acid supplement to make sure that the levels are correct when you’re looking for a pregnancy.
It is recommended to have a normal BMI, it should be between 18 and 25. It has been shown that variations in diet do not influence the results of ART. However, having a correct BMI before IVF treatment has been shown to improve the results. Patients with very low BMI could have an anovulation problem. On the other hand, patients with obesity may experience irregular cycles, increased risk of insulin resistance, miscarriage rates, and complications during pregnancy. Therefore, it’s recommended to contact a nutritionist when you have an abnormal BMI that can help achieve better results and support patients.
Vitamin D can be obtained from food, however, normally, it is insufficient, so it’s better to supplement it. Another source of vitamin D is the sun, then the best thing to do would be to spend at least 30 minutes under the sun, with arms and legs exposed to the sun. It plays an important role in calcium and phosphate metabolism.
Alcohol can have an inhibitory effect on the central nervous system, and this can affect the testicular level, irregular menses, and the quality of the oocytes. It could also create an increased DNA fragmentation of the spermatozoid in men so that the genetic material of the spermatozoids is altered, this can cause higher miscarriage rates. It could have an impact on morphology and sperm count. It is dose depended on the effect, normally, you shouldn’t be drinking more than 8 units of alcohol. One small glass of wine is 1.5 units more or less, Moderate intake of alcohol per week is not going to have a big impact on fertility.
Drugs like marijuana, cocaine and androgen steroids can also negatively impact gonadal function. Marihuana can cause problems with the motility and morphology of sperm in men. In women, there might be a higher risk of ectopic pregnancy, miscarriages, and fewer embryos to transfer. Cocaine during pregnancy can cause miscarriage and abruption of the placenta. Androgen steroids, on the other hand, can create azoospermia.
Smoking can again harm the quality of the eggs and sperm. In women, it can decrease ovarian reserve, impair tubal function, and increase the rate of miscarriages and placenta dysfunction. It can cause fewer oocytes for ART and embryos of lower quality. In men, it increases oxidative stress, DNA fragmentation, lower progressive motility, embryos of lower quality and lower pregnancy rate.
Chronic stress with increased glucocorticoids can decrease function (GnRH) and decrease libido. The impact of stress on Assisted Reproductive Techniques has not been demonstrated, it’s mostly because it’s not easy to do big randomized trials with psychological tests and patients, so there is no strong evidence to prove that.
Regarding exercise, it should be moderate, not strenuous. It can help regulate menstruation or help reduce insulin resistance. Too much exercise can create irregular cycles or amenorrhea or impact seminal parameters. However, it is important to mention that men should avoid cycling more than 5 hours per week and also avoid high temperatures like saunas. Moderate exercise can help reduce stress.
If you don’t succeed and have been trying to conceive for 6 months or so from 35 years old onwards, you should contact your doctor.
There’s no specific day for the follicle to start growing. It’s true that in some specific cases, we start stimulation when we do IVF, for example, or also when we do the insemination. Some people prefer to start on day two depending on every person, we start on day three, so we don’t have just one day in which these follicles start growing.
It’s more or less between day two and day three, there are no big differences. It depends on the environmental resource of the patient and what we want to do a lot. In insemination, I would start at day three and in someone that wants to do an IVF and has a low ovarian reserve, I would start on day two to avoid synchrony of the follicles.
FSH makes the follicles grow a little when they’re very small, but then these FSH levels are starting to decrease, and the follicle that is the dominant one because it has more receptors for the FSH than the other ones is going to keep all the FSH, and this one is the one that’s going to grow. How do we do it to make more than one grow? We do it by giving more FSH, we give external FSH to try to give it to all the follicles. It doesn’t mean that even if we give you a correct dose, all of them are going to grow because it depends a lot on your response, on every patient, it’s very different. We give more FSH to try to make all of them grow but making sure that it is safe for the patient.
How to define the FSH that we give daily with injections, IVF treatments or even with insemination? In insemination, we can also do a little stimulation to try to increase the outcomes. This is based on different things, the antral follicle count, age, weight, the body mass index, which is also important and also if you have done previous cycles. If you, for example, have done another cycle that went well or wrong, this can give us an idea of how to change it and which dose do you need or which kind of medication doesn’t work with you.
We can give more hormones, start the stimulation as soon as possible. When a patient has a low ovarian reserve, naturally, we have higher levels of FSH. Mostly what happens when we have a low ovarian reserve, and high FSH levels, the cycle shortens because the follicular growth starts before menstruation, and this can lead to a process in which we stimulate your ovaries, but one follicle has already been selected. Then we have what’s called asynchrony, even if we are giving you enough FSH.
To manage that, we normally give it before menstruation, before starting the IVF treatments if we think it is necessary, and it depends on every case and every patient.
The normal BMI would be between 18 and 25. Over 25, it’s a little overweight, but it’s not something that has been demonstrated that it can have an impact. What we do know is that a BMI of less than 18 could have an impact.
If it’s higher than 30, it could have an impact, and the best thing would be having a BMI of 25 maximum. 26-27, there’s no conclusive evidence that says that this can have an impact. It’s probably not going to be a bad BMI, but it’s also important to have a healthy lifestyle and exercise even if we are a little overweight, it can also help in that sense.
The probabilities of having good eggs at 44 are very low. After the age of 43, we start to recommend our patients to go for egg donation because we know that the probabilities of having success are very low, it’s less than 5%. It depends on every patient and AMH level, but we have to be very clear as the quality is related to age. This is the reason why we know that the probabilities will be low.
We cannot test the quality, if you have a good ovarian reserve at 44, I would ask you for more tests, the FSH levels, AFC, I would test more things to see how everything is, I would also ask if you have done treatments before or for how long you have been looking because it can give you also ideas.
The cytomegalovirus is a virus that can have a big impact if you get it while being pregnant. What we look at is the IgG antibodies and the IgM antibodies. If you have IgG antibodies that are positive before the pregnancy, it means that an IgM is negative, it means that you’re immunized so that you had this cytomegalovirus before, years before months before and that you are immune to it. It’s a virus that is very typical in children that go to kindergarten.
Probably you got that before, possibly because of your child or when you were little. IgG positive test if the IgM is negative means that you’re immune to it, you don’t have this high risk of getting it during pregnancy. There’s also the possibility of reactivation, but this is a low probability of impacting the baby, and it’s also not very frequent, so, in this sense, it is correct.
When it comes to Chlamydia, it could be something that you had in the past, for sure, you should look at it with your obstetrician. It’s better to test Chlamydia with a PCR test in the cervix because it’s more accurate. Some antibodies of Chlamydia can stay positive because you had it in the past, for example, or it can also be that there are some cross-reactions, and it’s a false positive, but it’s something that we should look at.
I think it’s just because you probably had it in the past, but it depends on which tests they have done and all your signs.
Regarding erythrocytes, we know that during pregnancy, we normally have a change in the hemogram. We can have anaemia, or the levels of immunoglobulin can be a bit lower. That’s also a reason why during pregnancy, we can do after the second trimester or from the second trimester, we can take iron supplements.
This is interesting because sometimes it could affect ovulation. The whole process that takes place in the ovulation and the endometrium needs some different metabolism and chemicals from the body to release this egg from the follicle, all this needs a lot of process with prostaglandins and different things.
Ibuprofen stops the prostaglandin, so it could have an impact. We tell our patients to avoid Ibuprofen during fertility treatments for that kind of reasons. If you’re trying to conceive naturally, and you if you take one pill once, it would be just bad luck if it affected the cycle.
We know that AMH drops, but it depends on every patient, we don’t know if you’re the one that’s going to have a big drop in one year or six months. There’s probably going to be a drop but not very important at 39, it still depends on every patient. At 40-42, every time, this drop is faster.
Sometimes people ask when they have a low ovarian reserve, is it that I had a very fast drop, or what happened? We cannot know if they had a very fast drop or if they had lower ovarian reserve from the beginning of their lives. We don’t know how fast your AMH will drop after 39 each year. If you’re thinking of trying to conceive, I would strongly recommend already starting to avoid any other problems with this decrease of ovarian reserve.
During ovulation, there’s like a movement of the genital tract, there can also be some contractions. Possibly when you ovulate, the ovaries are like moving a little, and this creates abdominal discomfort, if you have heavy abdominal pain for two days, or you have bladder pain, all these things probably are related to this ovulation.
Something has happened with your body because we are always changing, so it’s probably something to look at and do an ultrasound to make sure that everything is correct, that there’s no cyst or no other thing that could be giving you this pain. The body changes a lot, and the anatomy changes, also so it can vary. Some patients told me that when they had two children, then after having one child, their menstrual pains were worse. This happens because the body is continuously changing a little.
Yes, it’s something that we can see because when we have this progesterone created from the corpus luteum, it is because the central nervous system gives some pulses of LH continuously and there’s like disposes of during the little phase are variating. This can create a variation of the progesterone levels, but I would say if it’s more than 6, it is telling us that you’ve ovulated, and actually, these are correct levels of progesterone, so don’t worry about that.
What you should have is a normal carb diet, not excessive also not a low-carb diet. Have a lot of variety of fresh food more than processed food. It’s better to have a normal carb diet than a low-carb diet, I’m not a nutrition expert, but that’s what we normally recommend, and that’s what the evidence tells us.
If you had it once and after the egg retrieval, I think it’s not having a big impact on fertility. It’s a little controversial if it has an impact or not on the endometrium, but if it was only at the time, it’s not something that’s going to change it. Many clinics give Ibuprofen or some other kind of medications, and it’s not demonstrated that it has a big impact. It could have an impact on the ovulation processing in a natural cycle, but after one time or two times, I don’t think it will have an impact.
If it’s your first baby, normally it’s later, it’s like at the 20-24 week, and it could be even later, so don’t worry about that. In some cases, some patients tell us that they have felt it before at 17-18 weeks, it also depends on the person’s weight and where the placenta is because if it’s anterior, so the baby needs to do a very big movement so that you can feel it because the placenta is in between you and the baby. I would say with the first child, it’s between 20-24 weeks, with a second child, it normally is before, but it depends on where the placenta is located.
I would say between one and two coffees, it probably doesn’t have an important role. Caffeine and coffee have also antioxidants, so they could also be good. So having one or two cups of coffee a day would not be a problem when trying to conceive, and neither when you become pregnant nor during pregnancy, it should be okay.
Treatment with donor eggs is up to 50 years old before you turn 51. I would strongly recommend not waiting that long and trying before, even if you’re using an egg donor because pregnancy after 40 years or after 45 years can be a high-risk pregnancy, and you can have more preterm deliveries, hypertension, diabetes. The age limit for the general treatment is 50 years old in Spain.
When it comes to IVF with own eggs, there’s no limit at our clinic, I would say, but I would not recommend it if you are 44-45 and not if you are 46 years old and above. At 44-45, we could try if you had a very high ovarian reserve and considering all your previous medical history, I would probably recommend going for egg donation, but we could try it, but it depends on each patient.
At 44, 2 ng/ml would be a perfect AMH, I’m talking about nanograms millilitre, not picomoles. 1.5 ng/ml would be a very good number at such age as well. At 44, the AMH should normally be much lower than that.