Introduction

Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting approximately 10 percent of reproductive-age women and is a leading cause of infertility. Despite its significant impact, it remains underdiagnosed and inadequately managed. This review examines the pathophysiological mechanisms linking endometriosis and infertility, current treatment strategies, and the role of dietary and lifestyle interventions in optimizing reproductive outcomes.

Endometriosis is characterized by the presence of endometrial-like tissue outside the uterine cavity, primarily on the ovaries, fallopian tubes, and peritoneum. It is associated with chronic pelvic pain, dysmenorrhea, and infertility. The condition is classified into four stages based on the extent of the disease, with advanced stages showing a significant reduction in fertility rates.

Pathophysiology of endometriosis-related infertility

Several mechanisms contribute to infertility in women with endometriosis:

• Pelvic adhesions and anatomical distortion – Fibrotic adhesions impair tubal function and sperm-egg interaction.
• Diminished ovarian reserve – Ovarian endometriomas damage healthy ovarian tissue, leading to a reduction in the ovarian follicular pool.
• Inflammatory microenvironment – Elevated cytokines disrupt implantation and embryo development.
• Oxidative stress – Reactive oxygen species damage oocytes, impairing mitochondrial function and reducing fertilization potential.
• Altered immune function – Dysregulated immune responses compromise implantation.

Clinical management strategies

Surgical management: Laparoscopic excision and GnRH agonist therapy. Laparoscopic surgery is the gold standard for treating symptomatic endometriosis, aiming to restore normal pelvic anatomy and improve fertility. Postoperative administration of GnRH agonists has been shown to reduce recurrence rates and enhance pregnancy outcomes.

Hormonal suppression therapy. Hormonal interventions play a crucial role in symptom management and fertility preservation:

• GnRH agonists – Suppress disease progression and improve implantation rates in ART cycles.
• Progestin-only therapy – Used for long-term suppression and recurrence prevention post-surgery.
• Low-estrogen combined oral contraceptives – Preferred over high-estrogen formulations to avoid exacerbating lesion growth.

Nutritional and lifestyle interventions. Emerging evidence suggests that dietary modifications can mitigate inflammation and enhance fertility outcomes in women with endometriosis.

Anti-inflammatory diet

• Omega-3 fatty acids – Reduce inflammatory cytokine activity and are found in foods such as salmon, flaxseeds, and walnuts.
• Antioxidants – Neutralize oxidative stress and are abundant in citrus fruits, bell peppers, green tea, and dark chocolate.
• Curcumin – Found in turmeric, it helps inhibit inflammatory responses.
• Low-glycemic carbohydrates – Help stabilize insulin levels and reduce systemic inflammation, with sources including quinoa, legumes, and sweet potatoes.

Diagnosis: MRI vs. ultrasound in endometriosis

Accurate diagnosis is crucial for optimizing fertility treatment. The two primary imaging modalities include:

• Magnetic resonance imaging (MRI):

  • Highly sensitive for detecting deep infiltrating endometriosis
  • Superior for identifying retroperitoneal involvement and ovarian endometriomas
  • Useful for surgical mapping in advanced cases
  • Costly and time-intensive

• Transvaginal ultrasonography (TVUS):

  • First-line imaging tool due to affordability and accessibility
  • High specificity for endometriomas but less reliable for peritoneal lesions
  • Operator-dependent, affecting detection accuracy

A combined approach utilizing both MRI and TVUS enhances diagnostic accuracy and guides treatment decisions.

Treatment strategies for fertility optimization

1. Surgical intervention
   Laparoscopic excision of endometriotic lesions can:

   • Reduce inflammation and pain
   • Improve ovarian function
   • Enhance spontaneous conception rates

   However, repeated surgeries may compromise ovarian reserve, necessitating careful planning.

2. GnRH agonists at the time of surgery
   The use of GnRH agonists following laparoscopic surgery has been shown to:

   • Reduce recurrence rates
   • Increase pregnancy rates
   • Improve hormonal balance, enhancing fertility outcomes

   While intrauterine systems and GnRH agonists have individually shown efficacy, further research is required to establish their combined utility.

3. Ovulation induction with timed intercourse or intrauterine insemination (IUI)
   For mild endometriosis cases with patent fallopian tubes, ovulation induction using letrozole or gonadotropins enhances conception rates.

4. In vitro fertilization (IVF): The most effective option for severe cases
   IVF circumvents many disease-related barriers by:

   • Optimizing egg retrieval through controlled ovarian stimulation
   • Utilizing intracytoplasmic sperm injection (ICSI) to bypass sperm toxicity
   • Employing preimplantation genetic testing to select viable embryos

Management of endometriomas during egg retrieval: avoidance vs. decompression

Endometriomas pose significant challenges during oocyte retrieval. Clinicians must weigh the risks of puncturing these cysts against the benefits of decompression:

• Avoiding endometriomas minimizes risks such as infection, inflammatory responses, and reduced ovarian reserve.
• Decompression benefits include improved follicular access and reduced oxidative stress, though studies report mixed results regarding pregnancy outcomes.

The approach should be tailored based on cyst size, ovarian reserve, infection risks, and follicle accessibility.

Future directions in endometriosis and fertility treatment

Emerging research aims to refine therapeutic approaches, including:

• Stem cell therapy for ovarian rejuvenation
• Non-invasive biomarkers for early diagnosis
• Targeted immunotherapies to modulate inflammation without compromising fertility

Conclusion

Endometriosis remains a significant yet surmountable barrier to fertility. Early diagnosis, coupled with a tailored treatment approach—ranging from surgical intervention to assisted reproductive technologies—can significantly enhance reproductive outcomes. As research continues to unveil novel strategies, a multidisciplinary approach remains paramount in optimizing fertility outcomes for affected women.

Oluyemisi (Yemi) Famuyiwa is a renowned fertility specialist and founder, Montgomery Fertility Center, committed to guiding individuals and couples on their path to parenthood with personalized care. With a background in obstetrics and gynecology from Georgetown University Hospital and reproductive endocrinology and infertility from the National Institutes of Health, she offers cutting-edge treatments like IVF and genetic testing. She can be reached on Linktr.ee, LinkedIn, YouTube, Facebook, Instagram @montgomeryfertility, and X @MontgomeryF_C.