Antral follicle count measured at down-regulation as predictor of ovarian response and cumulative live birth: single center analysis including 2731 long agonist IVF cycles.

OBJECTIVE: Evaluate antral follicle count measured after pituitary suppression (AFCaps) with a GnRH agonist as predictor of ovarian response and cumulative live birth (CLB). METHODS: This study is a large cohort analysis of retrospective data between January 2011 and September 2020 in a tertiary-care university hospital. All first initiated IVF/ICSI cycles in women under 43 years of age for whom AFCaps was registered in our database were included. To evaluate CLB rates (CLBRs), only finalized cycles were analyzed (at least one live birth and/or all embryos transferred), excluding PGT cycles and severe male factor requiring testicular sperm extraction. RESULTS: AFCaps showed a good predictive ability in predicting ovarian response to ovarian stimulation. Predicting poor response, AFCaps presented an area under the receiver-operating characteristic curve (AUCROC) of 0.85 (95% CI 0.83-0.87), for high response prediction, the AUCROC was 0.80 (95% confidence interval [CI] 0.77-0.83).Although AFCaps was statistically higher in patients who achieved at least one live birth (13.6 ± 6.05 vs. 9.79 ± 6.33) and CLBRs per started cycle significantly increase between AFCaps quartiles (15.9%, 36.2%, 45.1% and 52.9%) its ability to predict CLBR was modest, with an AUCROC of 0.67 (95% CI 0.65-0.69). CONCLUSIONS: Women undergoing their first IVF/ICSI cycle following a long agonist GnRH protocol can be counseled with AFCaps measurement about their probability of achieving poor/high response. Based on this marker physicians can personalize ovarian stimulation with the aim of optimizing ovarian response and minimizing its risks. However, AFCaps has failed to predict CLB per started IVF cycle as an isolated marker.

The Follicular Output Rate (FORT) as a method to evaluate transdermal testosterone efficacy in poor responders.

OBJECTIVE: Follicular Output Rate (FORT) is an efficient quantitative and qualitative marker of ovarian responsiveness to gonadotropins. Transdermal testosterone (TT) has been used as adjuvant therapy to gonadotrophins in order to improve ovarian response in poor responders (PR). The aim of this study was to analyze whether TT can improve follicular sensitivity to gonadotropins using FORT. METHODS: This retrospective study, held in a tertiary-care university hospital included 90 PR patients, according to the Bologna criteria. Patients in Group 1 (n = 46) received transdermal application of testosterone preceding gonadotrophin ovarian stimulation under pituitary suppression. In Group 2 (n = 44) ovarian stimulation was carried out with high-dose gonadotrophin in association with minidose GnRH agonist protocol. We analyzed ovarian stimulation parameters and IVF outcomes. We determined antral follicle count (AFC) (3-8 mm) before ovarian stimulation, pre-ovulatory follicle count (PFC) (16-22 mm) and the day of hCG administration. We calculated the FORT using the PFCx100/AFC ratio. RESULTS: Baseline characteristics and ovarian reserve parameters were similar in both groups. FORT and oocytes retrieved were significantly higher in group 1 vs group 2. There were no significant differences in pregnancy rates. In group 1 there was a significant correlation between FORT and AFC. CONCLUSIONS: This study suggests that the potential beneficial mechanism of TT in poor responder patients may be based on increasing the antral follicle sensitivity to gonadotrophin. FORT is an excellent tool to demonstrate this.

Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency.

RESEARCH QUESTION: Could in-vitro action of follicles and fresh tissue autotransplantation without tissue culture (drug-free IVA) be useful in patients with primary ovarian insufficiency (POI)? DESIGN: Prospective observational cohort study in a tertiary university hospital. Drug-Free IVA was carried out in 14 women with POI with a median age of 33 years (29-36 years), median length of amenorrhoea of 1.5 years (1-11 years), median FSH levels 69.2 mIU/ml (36.9-82.8 mIU/ml) and anti-Müllerian hormone of 0.02 ng/ml (0.01-0.1 ng/ml). The surgical procedure included laparoscopic removal of ovarian cortex, fragmentation of tissue and autografting. Human menopausal gonadotrophin (HMG) was started immediately after surgery. RESULTS: Follicle development was detected in seven out of the 14 patients, and five women achieved successful oocyte retrieval. In six women, HCG was administered in 10 cycles. Six embryo transfers were carried out in five women resulting in four pregnancies; a clinical pregnancy rate of four in seven oocyte retrievals and four in six embryo transfers. CONCLUSIONS: Drug-free IVA could be a useful therapeutic option for patients with POI, leading to successful IVF outcomes.

Comparison of GnRH agonist versus luteal estradiol GnRH antagonist protocol using transdermal testosterone in poor responders.

OBJECTIVE: Transdermal testosterone has been used in different doses and in different stimulation protocols in poor responders. The aim of the present study is to compare the luteal estradiol/GnRH antagonists protocol versus long GnRH agonists in poor responder patients according to the Bologna criteria, in which transdermal testosterone has been used prior to the stimulation with gonadotropins. METHODS: In this retrospective analysis, a total of 141 poor responder patients according to the Bologna criteria were recruited. All patients were treated with transdermal testosterone preceding ovarian stimulation with gonadotropins during 5 days. In 53 patients we used the conventional antagonist protocol (Group 1). In 88 patients (GrH pituitary suppression was achieved by leuprolide acetate according to the conventional long protocol (Group 2). We analyzed the ovarian stimulation parameters and IVF outcomes. RESULTS: Comparing groups 1 and 2, there were no significant differences between cancellation rates and number of oocytes retrieved. However the total gonadotropin dose used and the mean length of stimulation were significantly lower in group 1 when compared to group 2. There were no significant differences in pregnancy outcomes; however, there was a slight increase in the implantation rate in group 1 vis-a-vis group 2, although statistical significance was not achieved. CONCLUSION: TT in poor responder patients can be effective both with the conventional agonist's long protocol and with the conventional antagonist's protocol. However, short regimes with previous estradiol antagonists in the luteal phase facilitate ovarian stimulation by shortening the days of treatment and the consumption of gonadotropins.