Obesity is surely one of the most important public health issues in the world today. In this webinar, Dr José Bellver, MD, Attending Gynecologist at IVI Clinic Valencia, explains the effect of female obesity on both spontaneous and assisted conception as well as its influence on pregnancy and the postnatal life of an offspring.
The definition of obesity is based on the body mass index (BMI). It is the relationship between weight and height in kilograms per square meter. A normal weight is considered to be up to BMI of 25. A BMI of over 25 to 30 is considered overweight. A BMI of 30 and above is considered obese and thus, a pathological condition.
The relation between obesity and conception problems
The medical world knows a lot of studies showing the relation between female obesity and an increased risk of both subfertility and infertility. While the former means that the time to achieve pregnancy is longer than expected, the latter describes the fact of not having any pregnancy at all. At the beginning of his presentation, Dr José Bellver introduces the study showing that the presence of obesity during adolescence is related to an increased risk of not having any pregnancy during lifetime or – if it eventually happens – no desired live birth because of several complications during pregnancy.
For many years, it has been believed that the exclusive mechanism related to subfertility and infertility in obese women is the presence of ovulatory disorders. However, there are studies suggesting that even in obese women with regular menstruations and normal ovulation, there is a significant reduction in spontaneous conception. Dr José Bellver admits that the deleterious effect on fertility is much stronger when both female and male obesity are combined and affecting the chances of a spontaneous conception. Unfortunately, it is quite common as both partners generally share the same lifestyle behaviours.
Obesity in reproductive medicine
As obese women present an increased risk of infertility, they are more prone to undergo treatments of assisted conception. However, they may encounter a few challenges along the assisted reproductive technologies (ART) route as well. According to Dr José Bellver, the first problem in case of obesity is the fact ovarian response to any kind of medication administered is reduced. It happens so due to several mechanisms. One of them is the higher volume of distribution of the drug, meaning that less amount of the drug reaches the target organ. Dr Bellver says that ovarian response to ovulation-stimulating drugs, such as gonadotropins and clomiphene citrate, is negatively correlated with the body mass index of the patient.
However, it is not the only problem. What’s even more important is the fact that obese women see much poorer results of IVF treatment. One decade ago, Dr José Bellver and his colleagues published a study on how obesity reduces uterine receptivity
and influences the effects of IVF. In their study – which turned out to be the largest single centre study performed – they analysed 6,500 cycles of IVF. If the body mass index of the patient was higher than 30, there was a significant reduction in all the parameters of the outcome, meaning implantation rate, pregnancy rates and live birth rates. In other words: the higher the body mass index of the patient, the higher the chances of not having a clinical intrauterine gestation. Similarly, there have been studies proving that the presence of male obesity in IVF contributes to reducing clinical pregnancy and live birth rates, too.
The decline in oocyte and uterine performance
It is a solid fact that pregnancy outcomes decline with increasing BMI. In order to learn if female obesity affects more the egg or the uterus, it is best to analyse ovum/egg donation treatments. In the ovum donation model, oocytes/eggs are taken from a donor, they are fertilised with the sperm of the partner and then the embryo that is obtained is introduced into the uterus of the recipient. Dr Bellver says that if the donor is normal weight and the recipient is obese, it is possible to observe the clinical effect of the obesity on the uterus. On the other hand, if the donor is overweight or obese and the recipient is normal weight, one can see what the clinical effect of obesity on the oocyte is. According to the available studies, if the donor has BMI between 25 and 34 (which means either overweight or obesity), there is a significant reduction in the clinical pregnancy rate in the recipient – which means there is a negative impact on the oocyte quality. However, if the donor is normal weight and there is female obesity in the recipient (from BMI of 30 to BMI of 40), pregnancy outcomes are declining as well. It means that female obesity in the recipient is altering the endometrial receptivity. That’s why, from a clinical point of view, obesity is affecting both oocytes and the uterus.
Dr José Bellver makes it clear: the presence of female and male obesity is deleterious for both spontaneous and assisted conception. Of course, it has to be noted that the role of women is more important here because it is female obesity that has the effect on all the following elements: oocytes, the uterus and pregnancy. In case of men, it is only the sperm that is affected. Knowing all of this, one has to determine the exact damage that obesity is exerting on both reproductive gametes, embryos and uterine receptivity.
Dr Bellver admits that the clinical studies aimed at determining if sperm quality
is altered in obese men, have not reached a consensus. Some of them have shown that in obese men, there are sperm alterations in terms of number, motility and morphology. The others, on the contrary, did not prove any alterations at all. The same refers to the relation between the men’s body mass index and embryo quality – there were no significant differences observed. When it comes to women, many studies have tried to ascertain if female obesity alters oocyte and embryo quality or not – but with no results. Despite the fact that there was a significant reduction in implantation, pregnancy and live birth rates when a patient’s BMI exceeded 30, the studies didn’t find any correlation between the body mass index and the embryo quality. Dr Bellver draws a conclusion that the methods used for determining gametes’ quality in the lab were simply not enough.
That’s the reason why new analysis techniques have emerged, such as e.g. embryo morphokinetics. Thanks to it, it has been observed that the embryo function was different in case of embryos coming from obese patients and normal weight patients. Dr Bellver says that from a morphological point of view, the culture media of embryos coming from obese women presented some differences in the metabolites, such as e.g. reduction in the percentage of saturated fatty acids. It means that, depending on a patient’s BMI, the same morphology embryos are working in a different way – and this results in various reproductive outcomes.
Similarly, attempts were made to determine what was happening in the endometrial receptivity due to female obesity. Having analysed the pattern of gene expression at the moment in which the embryo implanted, it has been observed that in obese women with PCOS, the expression is similar to other refractory conditions of the endometrium, such as the presence of a intrauterine device used for contraceptive purposes. Basing on the results of the endometrial receptivity
array (ERA) test, Dr Bellver and his team determined whether the percentage of non-receptive ERA test was in any way related to the presence of female obesity. It turned out that the presence of endocrine and metabolic disturbances in the body of obese women was altering the expression of the endometrial genes related to the embryo implantation.
Obesity vs. the development of pregnancy
Unfortunately, obese women may not only have problems with achieving pregnancy but also with keeping it. According to Dr José, in pregnancy of obese women there is an increased risk of miscarriage during the first semester. And it has been shown both in natural conception and in assisted conception after IVF. The main origin of first semester miscarriages is generally aneuploidy (the presence of embryos with chromosomal abnormalities) – but, in case of female overweight, a higher embryo aneuploidy is not being observed. However, the fact remains that even after transferring embryos with normal chromosomes, there was a significant increase in the clinical miscarriage rate in case of patients with high BMI. The explanation given by Dr Bellver is as follows: obese women present an increased risk of miscarriage not because of excessive chromosomal abnormalities in the embryos but due to the abnormal environment in which their embryos develop. This is the same reason why, in obese women, there is an increased risk of fatal and maternal complications during the three trimesters of pregnancy, including an increased risk of congenital anomalies. Additionally, due to the exposure to the abnormal environment with endocrine, metabolic and inflammatory alterations, the offspring of overweight or obese mothers is subjected to a number of chronic diseases in their postnatal life, such as e.g. type 2 diabetes, cardiovascular disorders, osteoporosis or asthma.
It is obvious that obesity increases the risk of developing a whole lot of diseases. As Dr Bellver has proved in this webinar, its adverse effect on fertility and pregnancy outcomes should not be underestimated. It has been proven that obesity not only impairs natural and assisted conception but also increases pregnancy complications and offspring diseases. That’s why the best measure to prevent or at least to minimise all the problems related to it is weight reduction before conception – as well as its reasonable management during pregnancy.