Diabetes, including both Type 1 (T1D) and Type 2 (T2D), is a chronic condition with significant implications for women’s reproductive health. This comprehensive review explores how diabetes affects female fertility, the diagnostic processes for infertility in diabetic women, steps to enhance fertility, and current treatment options, including the role of GLP-1 receptor agonists (GLP-1 RAs).

Impact of Diabetes on Female Fertility


Diabetes can cause several reproductive abnormalities in women, such as menstrual irregularities like oligomenorrhea (infrequent menstruation) and amenorrhea (absence of menstruation). These issues are often linked to poor glycemic control, a hallmark of unmanaged diabetes. Women with diabetes may also experience delayed menarche (first menstrual period) and premature menopause, shortening their reproductive period.

In women with T1D, menstrual irregularities are more frequent than in those without diabetes, influenced by the age of diabetes onset and glycemic control levels. Conversely, T2D in reproductive-age women presents additional health challenges, including increased cardiovascular risk and neuropathy, which indirectly affect fertility. Poorly controlled diabetes can impair ovarian function, affecting folliculogenesis (formation of ovarian follicles) and oocyte development, both crucial for fertility.

Diagnosis of Infertility in Women with Diabetes


Infertility is typically diagnosed after a couple fails to conceive after one year of regular, unprotected intercourse. For diabetic women, diagnosing infertility may require a comprehensive evaluation of the hypothalamic-pituitary-ovarian axis, hormonal status assessment, and screening for autoimmune disorders. Diagnostic tests often include:

  • Hormone-Level Blood Tests
  • Ultrasounds: To examine reproductive organs.
  • Laparoscopy: Sometimes used to identify physical abnormalities affecting fertility.

Steps to Improve Fertility in Women with Diabetes

Women with diabetes can take several proactive steps to enhance their fertility:

  • Glycemic Control: Maintaining optimal blood glucose levels is crucial. Improved glycemic control can help regulate menstrual cycles and enhance fertility rates.
  • Lifestyle Modifications: A healthy diet and regular exercise improve insulin sensitivity and reproductive health, contributing to better glycemic control.
  • Monitoring and Management: Regular blood glucose level monitoring, potentially with continuous glucose monitoring (CGM) devices, helps maintain stable glucose levels, beneficial for fertility.

Current Treatment Options for Infertility in Diabetic Women


Several treatment options are available for diabetic women experiencing fertility issues:

  • Medications:
    For women with polycystic ovary syndrome (PCOS), commonly associated with insulin resistance and diabetes, medications like metformin improve insulin sensitivity and stimulate ovulation. Clomiphene citrate and letrozole are other medications used to induce ovulation.
  • Assisted Reproductive Technologies (ART):
    In cases where medication alone is insufficient, ART, such as in vitro fertilization (IVF), may be considered.
  • Hormonal Treatments:
    Hormonal therapies can help regulate menstrual cycles and improve ovulation.
  • Surgical Interventions:
    Some cases may require surgical procedures to correct anatomical issues affecting fertility.

The Role of GLP-1 Receptor Agonists in Female Fertility


GLP-1 receptor agonists, such as liraglutide and exenatide, have potential benefits for women with obesity and PCOS, common causes of infertility. Studies show that GLP-1 RAs can lead to significant weight loss and testosterone level reductions, which can improve fertility outcomes in women with PCOS. However, the effects of GLP-1 RAs on insulin resistance and menstrual patterns have been mixed.

The fertility benefits of GLP-1 RAs are primarily linked to their weight loss effects, as weight reduction significantly influences fertility and pregnancy outcomes. Additionally, GLP-1 RAs may enhance insulin sensitivity and reduce cardiovascular disease risk, which is advantageous for women with PCOS.

Animal studies provide further insight into GLP-1’s role in fertility. In mice, GLP-1 receptor deletion results in disrupted estrous cycling and reduced fertility, highlighting a potential physiological role of incretin receptors in reproductive outcomes. Mice lacking GLP-1 receptors produce fewer litters than wild-type controls, emphasizing GLP-1’s importance in fertility.

However, GLP-1 RAs are not recommended during planned pregnancy due to potential risks, and more human studies are needed to understand their impact on fertility fully.

Conclusion 

Diabetes profoundly impacts female fertility, leading to menstrual irregularities and impaired ovarian function. Diagnosing infertility in diabetic women involves a thorough evaluation of hormonal and reproductive health. Managing blood glucose levels, adopting a healthy lifestyle, and exploring treatment options such as medications and ART can help many diabetic women overcome fertility challenges and achieve successful pregnancies. While GLP-1 RAs show promise in improving fertility outcomes, particularly in women with PCOS, further research is necessary to fully understand their role and ensure their safe use in women planning to conceive.Â