What are the optimal protocols for a patient with endometriosis undergoing a frozen embryo (FET - Frozen Embryo Transfer) replacement cycle?

From the Guidelines

For patients with endometriosis undergoing frozen embryo replacement cycle, a single embryo transfer (SET) is strongly recommended to minimize the risks of pregnancy complications and multiple gestations. This approach is supported by the most recent and highest quality study, which emphasizes the importance of SET in reducing the risks of ectopic pregnancy, neonatal death, and complications associated with multiple pregnancies 1.

Key Considerations

• The ESHRE guideline on the number of embryos to transfer during IVF/ICSI highlights the benefits of SET, particularly in patients with poor prognosis factors, such as advanced age, poor-quality embryos, and previous unsuccessful ART cycles 1.
• The study notes that transferring two embryos does not significantly improve cumulative live birth rates in poor prognosis patients and increases the risk of pregnancy complications and multiple gestations.
• Patients with endometriosis should be counseled about the risks and benefits of SET versus double embryo transfer (DET), including the increased risk of ectopic pregnancy and complications associated with multiple pregnancies.

Protocol Recommendations

• A hormone replacement therapy (HRT) protocol is generally recommended for patients with endometriosis undergoing frozen embryo transfer (FET) 1.
• The standard regimen includes estradiol valerate 2mg orally three times daily, starting on day 2-3 of the menstrual cycle, and continuing for approximately 12-14 days until the endometrial lining reaches 7-9mm thickness.
• Vaginal progesterone or intramuscular progesterone in oil is added once adequate endometrial development is achieved, and embryo transfer typically occurs after 5 days of progesterone for blastocyst-stage embryos.
• Consider adding a 2-3 month course of GnRH agonist prior to starting the FET cycle to suppress endometriosis activity and improve outcomes.

From the Research

Endometrial Preparation Protocols for Frozen Embryo Transfer Cycles in Women with Endometriosis

• The optimal endometrial preparation protocol for frozen embryo transfer (FET) cycles in women with endometriosis is still unclear 2, 3, 4.
• Studies have compared different protocols, including stimulated cycles, programmed cycles, natural cycles, and hormone replacement therapy (HRT) with or without gonadotropin-releasing hormone agonist (GnRHa) pretreatment 2, 3, 4.
• Some studies suggest that stimulated cycles may improve clinical pregnancy rates compared to programmed cycles 2, while others found no difference in pregnancy outcomes among different protocols 3, 4.
• GnRHa pretreatment has been shown to improve pregnancy outcomes in women with adenomyosis 5, but its effect on women with endometriosis is still unclear.

GnRHa Pretreatment and Pregnancy Outcomes

• A study found that long-term GnRHa pretreatment improved pregnancy outcomes in women with adenomyosis undergoing FET cycles 5.
• However, another study found that more injections of GnRHa had no advantage in pregnancy outcomes and may even increase the early miscarriage rate in women with endometriosis 3.
• The optimal number of GnRHa injections is still unclear, and more studies are needed to determine its effect on pregnancy outcomes in women with endometriosis.

Clinical Efficacy of Leuprolide Acetate in Treating Endometriosis

• Leuprolide acetate has been shown to reduce dysmenorrhea, dyspareunia, and chronic pelvic pain in women with endometriosis 6.
• However, it may cause weight gain and increase the risk of obesity-related diseases, particularly in obese patients 6.
• The expression of the MIF gene, which is involved in obesity, was found to be higher in obese women with endometriosis and increased after treatment with leuprolide acetate 6.

Pregnancy and Perinatal Outcomes

• Studies have found no difference in clinical pregnancy outcomes or prenatal outcomes among different endometrial preparation protocols for FET cycles in women with endometriosis 3, 4.
• Singleton live births were assessed for perinatal outcomes and obstetric complications, but no advantages or disadvantages were found among the different protocols 4.