Unlocking the Shocking Link Between Weight Loss and Infertility: What You Need to Know!

Infertility, a growing global health concern, affects a significant portion of the adult population. According to the World Health Organization (WHO), approximately 17.5% of adults worldwide faced infertility in 2023. Obesity, another escalating health issue, is associated with various chronic diseases, including infertility. This article explores the intricate relationship between weight loss, particularly medically induced weight loss, and its impact on fertility outcomes in both men and women.

The Interplay of Obesity and Infertility

Obesity is defined by the World Health Organization as “abnormal or excessive fat accumulation that may impair health,” resulting from an imbalance between calorie consumption and expenditure. Overweight is characterized by a Body Mass Index (BMI) over 25 kg/m2, while obesity is defined as a BMI over 30 kg/m2. Obesity can negatively impact both male and female fertility and reproduction.

Impact on Female Fertility

In women, obesity is linked to primary infertility outcomes such as:

Anovulation: The ovaries do not release an egg during the menstrual cycle. This is often due to dysregulation of the hypothalamic-pituitary-ovarian (HPO) axis and decreased amplitude of luteinizing hormone (LH) pulsatility.
Abnormal Reproductive Hormone Levels: Insulin resistance (IR) and hyperinsulinemia in obese women lead to reduced sex-hormone-binding globulin (SHBG) plasma concentrations and increased circulating free androgens and estrogen, suppressing follicle-stimulating hormone (FSH) release.
Impaired Endometrial Decidualization.
Decreased Pregnancy Rates: Obese women experience a 4-5% decrease in pregnancy rates.
Increased Time to Pregnancy: Achieving clinical pregnancy takes longer, especially when the BMI is over 35 kg/m2.
Lower Oocyte Yield: Morbidly obese women may have a lower oocyte yield due to altered mitochondrial function and endoplasmic reticulum stress in the oocyte.
Egg Quality: Research suggests that obesity can negatively impact the quality of eggs the ovaries produce.
Disrupted Hormonal Balance and Ovulation Cycles: Elevated estrogen levels due to excess adipose tissue can lead to irregular menstrual cycles, anovulation, and reduced fertility.
Insulin Resistance: Elevated insulin levels may stimulate the ovaries to produce excess androgens, contributing to conditions like polycystic ovary syndrome (PCOS).
Chronic Inflammation and Uterine Receptivity: Obesity is considered a state of chronic low-grade inflammation, affecting the uterus and making it difficult for an embryo to implant and develop into a pregnancy.
Increased Risk of Miscarriage and Poor ART Outcomes: Obese women have lower implantation rates and higher miscarriage rates. The live birth rate among obese women is lower compared to non-obese women following assisted reproductive technology (ART) treatment.

Impact on Male Fertility

In men, obesity contributes to infertility through:

Reduced Sperm Quality: Reduction in sperm concentration, morphology, and progressive motility.
Sexual Dysfunction: Fewer sexual encounters and erectile dysfunction (ED).
Increased Testicular Temperature.
Hormonal Imbalance: Increased estrogen and reduced testosterone plasma concentrations due to peripheral aromatization.
Poor Semen Parameters: Reduced sperm count, motility, and morphology.
Increased Oxidative Stress and DNA Fragmentation in Sperm.
Elevated Scrotal Temperature Affecting Sperm Production.
Higher Rates of Erectile Dysfunction and Decreased Libido.

Medical Weight Loss Therapies and Fertility

Several pharmacotherapies aim primarily at weight improvement. These include older drugs like orlistat and metformin, and newer medicines such as Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA). It is crucial to note that these medications are generally not recommended during planned pregnancy and should be discontinued in such cases.

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Orlistat

Orlistat is a gastrointestinal lipase inhibitor approved for long-term obesity management. Studies have shown that orlistat therapy can lead to:

Increased LH plasma concentrations.
Reduced free testosterone and anti-Müllerian hormone (AMH) concentrations.
Improved pregnancy rates.
Significant weight loss.
Improved hormonal profile in women with PCOS, including increased SHBG and reduced testosterone plasma concentrations.

However, a double-blind, placebo-controlled RCT found that orlistat-induced weight loss before IVF did not significantly improve live birth rates (LBRs).

Phentermine and Topiramate

Phentermine, a sympathomimetic amine, suppresses hunger and stimulates energy expenditure. Topiramate, an antiepileptic medicine, modulates central voltage-gated ion channels. The effects of this medical combination on primary fertility outcomes remain uncertain due to limited clinical experience and longer-term outcome data.

Metformin

Metformin, a biguanide antihyperglycemic medication, is used in diabetes mellitus (DM) therapy. Studies have indicated that metformin therapy can:

Improve body mass index, waist circumference, and insulin sensitivity.
Regulate menstrual cyclicity.
Reduce dehydroepiandrosterone-sulfate (DHEAS), testosterone plasma concentrations, and free androgen index (FAI).
Increase SHBG plasma concentrations.

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA)

Exenatide, dulaglutide, liraglutide, semaglutide, and tirzepatide are examples of GLP-1 RAs used for weight improvement. Exenatide, the first GLP-1 RA, has shown promise in:

Ameliorating the hormonal profile by increasing FSH and SHBG plasma concentrations and reducing testosterone serum concentrations.
Improving ovulation rates and menstrual cyclicity in women with PCOS.
Significant weight betterment, especially with combined therapy (e.g., metformin and exenatide).

The newer promising GLP-1 RAs show expectations regarding fertility improvement, as they have evidenced encouraging effects on improving ovulation rates and regulating the menstrual cycle. However, more human studies are needed to confirm this.

The Role of Lifestyle Factors

Lifestyle factors play an essential role in managing obesity and its impact on fertility.

Diet

A healthy diet, consisting of cereals, legumes, fruits, vegetables, and foods from animal sources, is crucial. Limiting energy intake from total fats and sugars and increasing the intake of healthy staples can benefit both weight management and fertility. Couples who consumed more seafood were able to get pregnant sooner than those who rarely ate seafood. Folic acid, vitamin B12, omega-3 fatty acids, and healthy eating plans like the Mediterranean diet have a positive impact on fertility in women.

Exercise

Consistent exercise is essential for maintaining long-term weight loss and preserving muscle mass. Physical activity and decreased sedentary behavior may improve fertility through the maintenance of a healthy body weight and hormonal levels. Aim for at least 150 minutes of moderate-intensity aerobic exercise per week.

Sleep

Adequate sleep plays an integral role in metabolic function, hormonal balance, and appetite control. Poor sleep can disrupt hormones like leptin and ghrelin, leading to insulin resistance and reduced glucose tolerance. Aim for more than 7 hours of sleep per night.

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Stress Management

Stress can influence the development of obesity through hormonal responses and behavioral changes. Techniques to manage stress, like mindfulness, can help foster a more positive relationship with food and exercise.

Weight Loss Benefits for Fertility

Weight loss, even as modest as a 5% to 10% reduction in excess weight can have a significantly positive impact on fertility for both men and women.

For women, weight loss can improve insulin sensitivity and restore balance in the HPG axis, leading to adequate levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are essential for egg development and ovulation.
Weight loss can also improve uterine receptivity and lead to better success with ART through higher pregnancy and live birth rates, fewer complications, and an improved response to medications.
For men, weight loss can result in reduced aromatase activity and estrogen, which helps increase testosterone levels, enhanced sperm parameters like concentration and motility, improved sexual function, and more.

Weight Change and Fertility: What the Evidence Suggests

While initial hope existed that weight loss might benefit fertility, recent evidence, including two large randomized controlled trials (RCTs), suggests that short-term weight loss does not increase fertility among overweight and obese women undergoing infertility treatment. However, observational evidence indicates that substantial weight gain between consecutive pregnancies, in the year prior to pregnancy attempt, and throughout adulthood is consistently harmful for time to pregnancy (TTP) and pregnancy maintenance.

Short-Term Weight Loss

Two large, well-conducted RCTs have shown that short-term weight loss for obese infertile women does not improve the outcomes of IVF cycles. However, overweight and obese anovulatory women may experience an increased likelihood of spontaneous pregnancy with weight loss.

Long-Term Weight Change

Observational cohort studies have found that the more weight a woman puts on between late adolescence and prior to pregnancy, the longer it takes her to get pregnant, and the higher her likelihood of pregnancy loss.

Recommendations

Maintain a Healthy Weight: Aim for a BMI between 18.5 and 24.9.
Moderate Weight Loss: Even modest weight loss (5% to 10% of excess weight) can positively impact fertility for women.
Healthy Lifestyle: Focus on an overall healthy lifestyle with exercise and good nutrition.
Avoid Weight Gain: Preventing weight gain is crucial for maintaining fertility.
Consult Professionals: Talk with a weight-loss specialist or healthcare provider for personalized guidance.

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