Episode 156: Obesity, Fertility, and Pregnancy Future Dr. Hamilton defines obesity and explains the pathophysiology of obesity and its effects on fertility and pregnancy. Dr. Arreaza adds some input about the impact of epigenetics on newborn babies. Written by Shelby Hamilton, MS3, American University of the Caribbean School of Medicine. Editing by Hector Arreaza, MD.
Episode 156: Obesity, Fertility, and Pregnancy
Future Dr. Hamilton defines obesity and explains the pathophysiology of obesity and its effects on fertility and pregnancy. Dr. Arreaza adds some input about the impact of epigenetics on newborn babies.
Written by Shelby Hamilton, MS3, American University of the Caribbean School of Medicine. Editing by Hector Arreaza, MD.
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Definition of obesity
Obesity is a multifactorial chronic disease that is increasing in prevalence across the globe. It can be defined as a body mass index (or BMI) greater than 30 kg/m2. According to the CDC from 2017-March 2020, the prevalence of obesity in United States adults was 41.9%.
Classification of obesity by BMI.
Obesity can further be divided into three classes: class I which is a BMI between 30-34.9; class II which is a BMI between 35-39.5; and class III which is a BMI greater than 40. We recommend avoiding the term “morbid obesity” because of the negative connotation of the word “morbid.” Class III or severe are better terms in those cases.
This classification is based on the individual risk of cardiovascular disease. One of the greatest health consequences affecting individuals with obesity is the cardiovascular effects including hypertension, dyslipidemia, and coronary artery disease. Other effects include insulin resistance and diabetes, cholelithiasis, non-alcoholic fatty liver disease, osteoarthritis, and even depression.
How Does Obesity Affect Fertility?
Obesity can have an extensive effect on the overall health of an individual. In addition to these commonly discussed effects, obesity can also influence a person’s fertility. This is especially observed in women with polycystic Ovary Syndrome (PCOS) who have a greater BMI and also have symptoms of anovulation. Excess adipose tissue plays a role in the effects that obesity has on fertility.
White adipose tissue can secrete a specific group of cytokines known as ‘adipokines’. These adipokines include leptin, ghrelin, resistin, visfatin, chemerin, omentin, and adiponectin. With a greater percentage of adipose tissue, there are higher rates of hypothalamic gonadotropin hormonal dysregulation, which can be combined with insulin-related disorders, low sex hormone binding proteins, and high levels of androgens. The combination of these factors can result in decreased ovarian follicle development and decreased progesterone levels.
Hormonal changes
Obesity is an endocrine disorder. One specific adipokine that affects the hypothalamic-gonadotropin axis is chemerin. Chemerin impairs the release of follicle-stimulating hormone (FSH) from the pituitary gland. This reduction in FSH release consequently leads to anovulation, meaning that no egg will be released from an ovarian follicle, contributing to infertility.
Shelby: Another adipokine affecting fertility is adiponectin. The receptors of adiponectin are predominantly expressed in reproductive tissues, including the ovaries and endometrium. In individuals with a greater BMI, a decrease in adiponectin secretion has been observed, resulting in decreased stimulation of its receptors, especially in the endometrium, which has been linked to recurrent implantation failure. Adiponectin has also been shown to affect glucose uptake in the liver. With reduced adiponectin levels, there is reduced hepatic glucose uptake, leading to insulin resistance. As tissues become less sensitive to insulin, the body compensates by secreting higher amounts of insulin, leading to hyperinsulinemia. Higher levels of circulating insulin have also been proven to cause hyperandrogenemia in women by blocking the hepatic production of sex hormone-binding globulin.
Insulin can also act on the IGF-1 receptors in the theca cells, increasing steroidogenesis, and thus, increasing androgens. With hyperandrogenemia, there is also increased granulosa cell apoptosis as well as increased peripheral conversion of androgens into estrogen. This creates negative feedback to the hypothalamic-pituitary axis to decrease the release of gonadotropins such as FSH which are critical in ovulation.
Leptin is another adipokine that is shown to be increased in obesity. Studies on mice have shown that leptin impairs the development of ovarian follicles, resulting in a decrease in ovulation. In these studies, it was also observed that leptin reduces the production of estriol by the granulosa cells in the ovarian follicles as well as increases the rate of apoptosis in granulosa cells, both of which affect ovulation. Leptin decreases hunger, but persons with obesity may be resistant to its effects and that’s why they have higher levels than a person with normal weight. They have high levels of leptin but are still hungry because they have leptin resistance.
Studies have also shown that the fatty acid composition of follicular fluid found in ovarian follicles also plays a role in fertility. In individuals with a high BMI, this fluid contains high levels of oleic acid, which can cause embryo fragmentation after fertilization occurs. Stearic acid is another fatty acid found in elevated levels in the follicular fluid of women with a greater BMI, which can also affect the quality of the embryo while in the blastomere stage.
The bottom line is obesity decreases fertility. It does not mean that patients with obesity will not get pregnant, but it can make it harder to get pregnant. Female patients who are losing weight must be warned about their improved fertility once they start to lose weight.
What effect does obesity have on pregnancy?
While obesity may make it more difficult for a woman to get pregnant, it is not impossible. However, there are potential risks both to the mother’s health as well as the baby’s health. Therefore, it is very important to monitor these patients even more carefully.
Women who have a greater BMI pre-pregnancy are at a greater risk of developing gestational hypertension. Gestational hypertension is defined as blood pressure greater than 140/90 on more than one reading in the second half of pregnancy. Hypertension during pregnancy can also have serious complications such as kidney failure, stroke, myocardial infarction, or even heart failure. Gestational hypertension can also result in preterm birth or low birth weight.
Treatment of mild hypertension in pregnancy
Recent studies published in the AFP Journal support the treatment of mild hypertension in pregnancy. It states that “evidence and expert opinion support treating mild chronic hypertension in pregnancy with approved antihypertensives, with a strength of recommendation: B”. There was a randomized control trial with about 2,000 women who were randomized to receive antihypertensive treatment vs no treatment. The treatment group had a lower incidence of preeclampsia with severe features, preterm birth, placental abruption, and neonatal or fetal death. There was not an increase in fetal growth restriction or maternal or neonatal complications. So, it is advisable to treat chronic, mild hypertension in pregnancy, according to the AFP Journal.
Preeclampsia
Preeclampsia is another condition that is at a higher risk in women with obesity, which is a more serious manifestation of hypertension in the second half of pregnancy. Along with high blood pressure, there are also effects on the kidneys and liver. Hypertension accompanied by proteinuria is indicative of preeclampsia and should be taken seriously. Preeclampsia can become eclampsia, where the patient also experiences seizures. There is also the risk for stroke, HELLP syndrome, placenta abruption, preterm birth, and fetal growth restriction.
Gestational diabetes
Another risk is gestational diabetes. Elevated blood glucose during pregnancy can result in a larger baby and delivery by cesarean. There may also be a greater risk of the mother and child developing diabetes mellitus later on in life.
OSA
Women with a greater BMI may also be at risk of developing obstructive sleep apnea during pregnancy. Not only can this result in fatigue but can also contribute to the development of gestational hypertension and preeclampsia.
Effect of obesity on the fetus
As mentioned, there are some risks to the fetus in women with a greater pre-pregnancy BMI. There is a greater risk for these babies to be born with birth defects such as congenital heart defects and neural tube defects. Another risk previously discussed is macrosomia, or large for gestational age. Larger babies are also at increased risk for shoulder dystocia during delivery as well as resulting clavicle fractures, brachial plexus injuries, and nerve palsies. Preterm birth is another risk, which also increases the risk of short-term and long-term health complications. Lastly, a higher BMI is directly correlated with the risk of spontaneous abortion or stillbirth.
Summary
As the prevalence of obesity increases, it is important to discuss the health risks that are associated with this disease. In our patients of childbearing age and who may be hoping to conceive, it is even more important to discuss how a higher BMI may affect fertility and pregnancy. While discussing these topics with patients, it is important to try our best to build rapport with the patient so that the discussion is seen more as one of concern and support rather than one of criticism regarding their weight. We may want to help by not only telling patients to “lose weight” or “diet”, but we can also provide them with resources regarding dietary adjustments and ways they can incorporate physical activity into their lives without just telling them to eat less and move more. Stay tuned for our episode on the management of obesity in pregnancy.
Conclusion
Now we conclude episode number 156, “Obesity, fertility, and pregnancy.” Future Dr. Hamilton explained how obesity affects the hormonal regulation of fertility. She also explained the obstetrical risks associated with obesity. Primary care professionals need to educate our patients about the benefits of preconception weight control. Dr. Arreaza explained that hypertension is a common condition in pregnant patients with obesity and mentioned the benefits of treating mild hypertension in pregnancy. We hope to bring you an episode on the management of obesity in pregnancy soon, so stay tuned!
This week we thank Hector Arreaza and Shelby Hamilton. Audio editing by Adrianne Silva.
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