From the Guidelines
Luteal phase progesterone supplementation after Letrozole treatment is crucial for improving fertility and pregnancy rates, as it compensates for potential luteal phase defects caused by the medication. The use of Letrozole for ovulation induction can result in inadequate corpus luteum function, leading to insufficient hormonal support for implantation and early pregnancy maintenance 1. Progesterone supplementation helps support the endometrial lining and early pregnancy, potentially increasing pregnancy success rates by 5-10% compared to cycles without supplementation.
Recommended Approach
The recommended approach is to start progesterone supplementation after ovulation is confirmed, typically 3 days after a positive ovulation predictor kit or after documented ovulation via ultrasound. Common regimens include:
- Vaginal progesterone (Endometrin 100mg twice daily, Crinone 8% gel once daily, or micronized progesterone 200mg twice daily)
- Intramuscular progesterone in oil (50mg daily) Supplementation should continue until 10-12 weeks of pregnancy if conception occurs, or until menstruation begins if no pregnancy occurs.
Rationale
Letrozole works by temporarily reducing estrogen production, which increases FSH release and stimulates follicle development 1. However, this process can sometimes result in inadequate corpus luteum function, making progesterone supplementation essential for supporting implantation and early pregnancy maintenance. The use of Letrozole does not reduce the number of mature oocytes obtained or their fertilization capacity, and no effect on congenital abnormality rates in children has been observed 1.
Key Considerations
- Ovarian stimulation with gonadotropins is required for oocyte and embryo cryopreservation, followed by follicle aspiration 1.
- The efficacy of oocyte and embryo cryopreservation to generate a subsequent pregnancy is tightly connected to the number of mature oocytes retrieved after ovarian stimulation 1.
- Recent data reported a cumulative live birth rate of 61.9% if 12 oocytes were cryopreserved in women 35 years of age and 43.4% if 10 oocytes were cryopreserved in women >35 years of age 1.
From the Research
Effects of Luteal Phase Progesterone Levels after Letrozole on Fertility and Pregnancy Rates
- The study 2 found that letrozole was associated with significantly higher clinical pregnancy and live birth rates per woman compared to clomiphene in treatment-naïve infertile women with PCOS.
- Another study 3 found that luteal phase support using intravaginal progesterone was associated with a 10% higher pregnancy rate, although this difference did not reach statistical significance.
- The study 4 found that letrozole co-treatment during ovarian stimulation with gonadotrophins for IVF increased mid-luteal progesterone levels, which may contribute to optimizing the luteal phase endocrinology.
- However, the study 5 found that luteal phase support with vaginal progesterone supplementation did not have a beneficial effect on β-hCG positivity and clinical pregnancy rates in women undergoing IUI.
- The study 6 found that letrozole cotreatment induced marked changes in both the follicular and luteal phase endocrinology, causing potentiation of follicle diameter and an improved corpus luteum function without affecting the secondarily recruited follicle cohort.
Luteal Phase Progesterone Levels and Pregnancy Outcomes
- The studies 3, 4, 6 suggest that luteal phase progesterone levels may play a role in pregnancy outcomes, with higher levels potentially contributing to improved pregnancy rates.
- However, the study 5 found no beneficial effect of luteal phase support on pregnancy outcomes, highlighting the need for further research in this area.
Letrozole and Fertility Treatment
- The studies 2, 3, 4, 6 suggest that letrozole may be a useful adjunct to fertility treatment, particularly in women with PCOS or those undergoing IVF.
- Letrozole co-treatment may improve follicle growth, increase androgen production, and optimize luteal phase endocrinology, potentially leading to improved pregnancy outcomes.