From the Guidelines
Referral to a Reproductive Endocrinology and Infertility (REI) specialist should be considered after 3-6 unsuccessful cycles of letrozole treatment for ovulation induction, as letrozole has demonstrated its maximum effectiveness within these treatment windows 1. If a patient under 35 years old has not conceived after 6 cycles of letrozole, or if a patient over 35 has not conceived after 3-4 cycles, REI referral is appropriate. Additionally, immediate referral is warranted in cases of known tubal disease, severe male factor infertility, or if the patient has a history of multiple pregnancy losses despite letrozole therapy. Patients with diminished ovarian reserve or those approaching advanced reproductive age (>38 years) should be referred sooner rather than later. The rationale for these timeframes is that letrozole, which works by inhibiting estrogen production and thereby increasing follicle-stimulating hormone to stimulate ovulation, has demonstrated its maximum effectiveness within these treatment windows, and continuing the same treatment beyond these timeframes without additional interventions is unlikely to significantly improve outcomes and may delay access to more advanced reproductive technologies like intrauterine insemination or in vitro fertilization that an REI specialist can provide 1. Some studies have shown that ovarian stimulation for fertility preservation has no adverse effect on survival in women with breast cancer or other malignancies, and the use of letrozole does not reduce the number of mature oocytes obtained or their fertilisation capacity 1. Key factors to consider when referring to an REI specialist include:
- Age of the patient
- Number of unsuccessful cycles of letrozole treatment
- Presence of known tubal disease or severe male factor infertility
- History of multiple pregnancy losses despite letrozole therapy
- Diminished ovarian reserve or advanced reproductive age
- The potential benefits and risks of ovarian stimulation for fertility preservation, including the use of letrozole and other hormonal stimulation regimens 1. It is essential to weigh these factors and consider referral to an REI specialist to provide the best possible outcomes for patients undergoing letrozole treatment for ovulation induction 1.
From the Research
Referral to Reproductive Endocrinology and Infertility (REI) after Letrozole Treatment
- The decision to refer to REI after letrozole treatment depends on various factors, including the patient's response to treatment, ovulation induction, and pregnancy outcomes 2, 3, 4, 5, 6.
- Studies have shown that letrozole is an effective treatment for ovulation induction in women with polycystic ovary syndrome (PCOS) 2, 3, 4, 5, 6.
- However, the referral to REI may be considered if the patient:
- Fails to ovulate or conceive after multiple cycles of letrozole treatment 3, 4.
- Experiences recurrent miscarriages or failed pregnancies 5, 6.
- Has a history of ovarian hyperstimulation syndrome (OHSS) or other complications related to ovulation induction 4, 6.
- Requires further evaluation and management of underlying fertility issues, such as tubal damage or male factor infertility 2, 3.
- The American Society for Reproductive Medicine (ASRM) recommends that women with PCOS who fail to conceive after 6-12 months of ovulation induction with letrozole or other medications be referred to an REI specialist for further evaluation and treatment 6.
Factors Influencing Referral to REI
- Patient's age and reproductive history 2, 3.
- Presence of other fertility-related issues, such as endometriosis or unexplained infertility 4, 5.
- Response to letrozole treatment, including ovulation induction and pregnancy outcomes 2, 3, 4, 5, 6.
- Patient's preferences and values regarding fertility treatment options 5, 6.
Benefits of Referral to REI
- Access to specialized care and expertise in reproductive endocrinology and infertility 2, 3, 4, 5, 6.
- Comprehensive evaluation and management of underlying fertility issues 2, 3, 4, 5.
- Increased chances of conception and live birth rates with advanced fertility treatments, such as in vitro fertilization (IVF) 5, 6.