Is letrozole during ovarian stimulation useful in breast cancer patients undergoing fertility preservation to reduce early luteal progesterone levels following GnRH-agonist trigger?

BACKGROUND: In absence of contraindication, breast cancer patients of reproductive age can undergo fertility preservation with controlled ovarian stimulation for oocyte/embryo cryopreservation before the administration of potentially gonadotoxic treatments. High hormonal levels induced by ovarian stimulation might have an adverse impact on hormone-positive breast cancer. Whether letrozole supplementation during ovarian stimulation (COSTLES) reduces serum progesterone levels after GnRHa trigger remains unknown. We aimed to determine whether COSTLES might be useful for breast cancer patients undergoing fertility preservation to reduce early luteal progesterone levels following GnRH-agonist (GnRHa)trigger. METHODS: All women who underwent COS with GnRH antagonist protocol with GnRHa trigger were included. Serum progesterone level measured 12 h after GnRHa trigger was compared between patients undergoing COS with letrozole supplementation (COSTLES group) and patients undergoing COS without letrozole (Control group) for fertility preservation purposes. RESULTS: A total of 246 patients were included, of which 84 patients (34.1%) in the COSTLES group and 162 patients (65.6%) in the Control group. All patients in the COSTLES group were BC patients (n = 84, 100%), while the Control group included 77 BC patients (47.5%). Patients in the two groups were comparable. The mean number of oocytes recovered and vitrified at metaphase 2 stage did not significantly differ between the two groups. Serum progesterone levels on the day after GnRHa trigger were significantly lower in the COSTLES group (8.6 ± 0.7 vs. 10.5 ± 0.5 ng/mL, respectively, p < 0.03), as well as serum E2 levels (650.3 ± 57.7 vs. 2451.4.0 ± 144.0 pg/mL, respectively, p < 0.01). However, the GnRHa-induced LH surge was significantly higher in in the COSTLES group (71.9 ± 4.6 vs. 51.2 ± 2.6 UI/L, respectively, p < 0.01). CONCLUSIONS: Our results show that COSTLES for fertility preservation in breast cancer patients using GnRHa trigger reduces serum progesterone levels compared to ovarian stimulation without letrozole. These findings encourage the use of COSTLES in this context to decrease the potential deleterious effect of elevated hormonal levels on hormone-positive breast cancer.

Efficacy of tocopherol and pentoxifylline combined therapy for women undergoing assisted reproductive treatment with poor endometrial development: a retrospective cohort study on 143 patients.

Poor endometrial development during in vitro fertilization remains challenging. Indeed, no broadly accepted definition of poor endometrial development exists, and no treatment has shown any improvement in the condition. The aim of this study was to analyze whether treatment with a combination of pentoxifylline and tocopherol increases endometrial volume. This monocentric and retrospective study includes patients with previous miscarriages, in vitro fertilization failure, or poor endometrial development. The patients had an ultrasonography during the mid-luteal phase to assess both endometrial thickness and endometrial volume (EV). If the volume was less than 2 mL, they were given pentoxifylline (PTX) and tocopherol for at least 2 months before a second ultrasound assessment. One hundred and forty-four patients were analyzed. The mean duration of treatment was 132 days. The combination of tocopherol and PTX significantly increased the EV by 0.47 mL (p < 0.0001; 95% CI 0.38-0.57). The mean ± SD EV was 1.34 ± 0.38 mL and 1.82 ± 0.63 mL before and after the treatment respectively. No data concerning pregnancy rates were interpretable. We showed an improvement of poor endometrial proliferation with a treatment including PTX and tocopherol. These promising results should be followed up by a prospective study.

Anti Müllerian Hormone: More than a biomarker of female reproductive function.

Anti-Müllerian hormone (AMH), known for its role during sexual differentiation, is a dimeric glycoprotein that belongs to the transforming growth factor-ß (TGF-ß) family. AMH has recently been identified as a reliable marker of ovarian reserve that can help predict early ovarian follicle loss and menopause onset. AMH levels also reflect the effects of damaging gynecologic surgeries or gonadotoxic treatments such as chemotherapy on ovarian reserve. Furthermore, AMH participates in the diagnosis of certain diseases such as granulosa cell tumors or Polycystic Ovary Syndrome (PCOS). Currently used to establish patient profiles and predict ovarian response to stimulation, its role in ART techniques is crucial. Nevertheless, AMH appears to be a weak independent predictor of qualitative outcomes such as implantation, pregnancy, and live birth. As the reliability and reproducibility of AMH dosage have raised many doubts due to different existing standards and thresholds, an international consensus is still expected to improve AMH measurement and interpretation.