By: Rebecca Bremer
Editor’s Note: Although this is a summary of an article [1] published in 2002, it highlights the importance of responding to good research by applying its findings in clinical practice. Twenty-three years have passed and we have an epidemic of obesity and its consequences. The primary care specialties (family medicine, internal medicine, pediatrics, and gynecology) have traditionally shouldered the task of educating patients on the impact of lifestyle choices (e.g., sleep, nutrition, physical activity, tobacco use) on their health and fertility. Given the validated results from decades of research on the impact of lifestyle on multiple health outcomes, all medical specialties must engage patients in meaningful dialogue about lifestyle choices to prevent disease, restore fertility, and help them lead healthier lives.
Introduction
In the United States, the obesity epidemic has created a ripple effect in different areas of medicine. The impact of obesity on reproductive health is often overlooked, and the negative effect of obesity on a couple’s ability to conceive is still widely underestimated. The article by Crosignani [1] summarized below was a comprehensive review of the available literature at the time to assess the effect of obesity or being overweight on spontaneous and induced fertility, as well as the positive impact of weight loss on the same measures.
Weight Impacts Ovulation and Fertility
The author began by discussing the general effects of obesity on ovulation and spontaneous fertility. Several studies found that being overweight is associated with menstrual irregularities, anovulation, infertility, and polycystic ovary syndrome (PCOS). [2] One study found that a BMI greater than 27 had a relative risk of 3.1 for primary ovulatory infertility compared to those with BMI less than 27. [3] The study also identified that the risk of infertility was even greater in women who were overweight and had PCOS.
“Being overweight is associated with menstrual irregularities, anovulation, infertility, and polycystic ovary syndrome (PCOS).”
Beyond the impact of weight, body fat distribution can have a detrimental effect on a woman’s menstrual cycle. [4] A study found that women with a waist-to-hip ratio of less than 0.8 (described as pear-shaped) had the highest rate of pregnancy, whereas women with a larger waist-to-hip ratio (described as apple-shaped) had significantly lower rates of spontaneous pregnancy. [5]
Being overweight decreases sex hormone binding globulin (SHBG), which increases circulating androgen concentrations, leading to increased insulin secretion and resistance. [6] Both the elevated androgen secretion and insulin concentrations play a role in the distribution of body fat. Patients with obesity, hyperandrogenism, and acanthosis nigricans — a sign of insulin resistance — had the highest waist-to-hip ratio and, thus, the highest risk of infertility and cycle irregularity. [1]
Another negative effect of obesity is the increased difficulty of ovarian stimulation and ovulation induction for individuals who are overweight. Obese patients were found to be less responsive to ovulation induction with clomiphene citrate and required a higher dose.[7] In in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, the use of low dose gonadotropins in overweight patients led to lower ovulation rates, higher miscarriage rates, and suboptimal ovarian response. [1]
The Good News!
Although there is strong evidence of harmful effects of obesity on fertility, the evidence also reveals that weight loss can quickly re-establish ovulation and improve pregnancy rates. One study discussed in Crosignani et al’s article [1] showed that after 10-15% weight loss, 90% of the women resumed ovulation, 30% achieved spontaneous pregnancy, and 40-50% achieved drug-induced pregnancy. [8]
“The evidence also reveals that weight loss can quickly re-establish ovulation and improve pregnancy rates. One study … showed that after 10-15% weight loss, 90% of the women resumed ovulation (and) 30% achieved spontaneous pregnancy.”
Other pro-fertility benefits of weight loss include decreased insulin, androstenedione, DHEA, and estradiol concentrations. [9] With lower circulating androgens, the concentration of SHBG increased, which enhanced insulin sensitivity and led to a lower waist-to-hip ratio in women’s body fat distribution. [1] Weight loss was also shown to lower ovarian volume and consistently improve menstrual cyclicity. [1] The authors noted that in the studies demonstrating weight loss benefit, patients who did not lose weight showed no improvement in the identified factors.
The authors also noted the benefit of metformin on ovulation and fertility. Given the proven link between insulin resistance and anovulation in obese patients, the benefit of an insulin-sensitizing agent like metformin to restore reproductive health is an important consideration in this population. [10] Overall, the studies reviewed in the article showed metformin restored menstrual cycles, improved spontaneous and clomiphene-induced ovulation, and decreased levels of serum insulin, testosterone, and leptin. [1] These benefits were independent of weight reduction. The use of metformin during pregnancy in patients with both obesity and PCOS showed decreased first-trimester pregnancy loss and a lower risk of gestational diabetes. [11]
Conclusion
Crosignani et al [1] provided an in-depth review of various articles that brought to light many important factors regarding obesity. As physicians, it is crucial to understand the precise negative effects of obesity on reproductive health as well as the positive impact of weight reduction in this population. The promising evidence in the article highlights that for people who desire conception, counseling on weight reduction through changes in diet and exercise is essential. Weight reduction will not only improve their overall health but their fertility as well. It could also help them avoid frustration and disappointment, and save time and money.
“For people who desire conception, counseling on weight reduction through changes in diet and exercise is essential, (as) weight reduction will not only improve their overall health but their fertility as well.”
Crosignani et all wrote the article in 2002; since then, numerous studies delved deeper to further investigate the same topics. For example, the authors hoped for larger controlled studies on the benefits of metformin in overweight patients, and much more research has been in this area. Decades later, the information presented can still help guide discussions with patients on the risks of being overweight to their reproductive health, and which lifestyle changes can reverse those effects.
Editor’s Note: To learn more about the impact of lifestyle factors such as nutrition, exercise, and sleep on reproductive health and fertility, plan to attend the FACTS Virtual Conference this fall, October 10-11, 2025! It will be preceded by a self-directed, online pre-conference to build an even stronger foundation.
References
[1] Crosignani PG, Vegetti W, Colombo M, Ragni G. 2002. Resumption of fertility with diet in overweight women. Reproductive BioMedicine Online. 5, 60-64.
[2] Reid RL, Van Vugt DA. 1987. Weight-related changes in reproduction function. Fertility and Sterility. 48, 905–913.
[3] Grodstein F, Goldman MB, Cramer DW. 1994. Body mass index and ovulatory infertility. Epidemiology. 5, 247–250.
[4] Hartz AJ, Rupley DC, Rimm AA. 1984. The association of girth measurements with disease in 32,856 women. American Journal of Epidemiology. 119, 71–80.
[5] Zaadstra BM, Seidell JC, Van Noord PA et al. Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. British Medical Journal. 306, 484–487.
[6] Kiddy DS, Sharp PS, White DM et al. Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases. Clinical Endocrinology (Oxford). 32, 213–220.
[7] Imani B, Eijkemans MJ, te Velde ER et al. Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Journal of Clinical Endocrinology and Metabolism. 83, 2361–2365.
[8] Clark AM, Roberts B, Galletley C et al. 2000. Maximizing weight loss in the overweight infertile patient – a prospective randomized controlled trial. Human Reproduction. 15, 65–66.
[9] Hollmann M, Runnebaum B, Gerhard I. 1996. Effects of weight loss on the hormonal profile in obese, infertile women. Human Reproduction. 11, 1884–1891.
[10] Barley CJ, Turner RC. 1996. Metformin. New England Journal of Medicine. 334, 574–579.
[11] Jakubowicz DJ, Iuorno MJ, Jakubowicz S et al. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism. 87, 524–529.
ABOUT THE AUTHOR
Rebecca Bremer, DO
Rebecca Bremer, DO was a fourth-year medical student at Michigan State University College of Osteopathic Medicine when she wrote this review. Since then, she completed residency in obstetrics and gynecology. She took the FACTS elective during her fourth year to be better educated on the different ways she can help her future female patients.
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