The aim of this article is to describe unexpected spontaneous pregnancies in poor responder patients with long-term infertility, when treated with dehydroepiandrosterone (DHEA) supplementation prior to in vitro fertilization (IVF). Our evaluation was carried out in two groups of women. The first group included 39 young women with <40 years, all treated with DHEA because of a previous poor response. The second group included 38 women over 40 years who received DHEA supplementation. Controls for latter group were 24 comparable women who had not been treated with DHEA before the first IVF cycle to evaluate the spontaneous pregnancy rate during preparation to IVF. Three tablets daily of 25 mg micronized DHEA were administered for at least 12 weeks before starting a long stimulation protocol for IVF. Surprisingly, spontaneous pregnancy rate significantly increased after DHEA treatment, allowing to achieve 10 spontaneous pregnancies and 9 spontaneous ongoing pregnancies among young poor responders. Pregnancy rate and ongoing pregnancy rate obtained before starting the IVF cycle were also significantly higher in older women treated with DHEA than in the control group: 21.05% and 13.15% and 4.1% and 0, respectively. Our results show that DHEA supplementation improves the ovarian function in poor responders and in women over 40 years, suggesting that this molecule alone can raise fecundity and fertility treatment success in women with poor prognosis for pregnancy.

SUMMARYSpermatozoa can be retrieved in non-obstructive azoospermia (NOA) patients despite the absence of ejaculated spermatozoa in their semen because of the presence of isolated foci with active spermatogenesis. Conventional testicular sperm extraction (c-TESE) in patients with NOA has been partially replaced by micro-TESE. It is still under debate the problem regarding the higher costs related to micro-TESE when compared with c-TESE. In this study, we evaluated sperm retrieval rate (SRR) of c-TESE in naive NOA patients. Sixty-three NOA patients were referred to our centre for a c-TESE. For every subject, we collected demographic data, cause of infertility, time to first infertility diagnosis, serum levels of LH, FSH, total testosterone and prolactin. A statistical analysis was conducted to correlate all the clinical variables, the histology and the Johnsen score with the SRR. Sixty-three consecutive NOA patients with a mean age of 37.3 years were included. The positive SRR was 47.6%. No statistical differences were observed between positive vs. negative SRR regarding mean FSH (17.12 vs. 19.03 mUI/mL; p = 0.72), and LH (9.72 vs. 6.92 mUI/mL; p = 0.39) values. Interestingly, we found a statistically significant difference in terms of time to first infertility diagnosis (+SRR vs. ÀSRR; 44.5 vs. 57 months; p = 0.02) and regarding to age (+SSR vs. ÀSRR; 40.1 vs. 35.3; p = 0.04). There was a statistically significant decrease in SRRs with the decline in testicular histopathology from hypospermatogenesis to maturation arrest, and SCO. The mean Johnsen score was 5.9 with a mean percentage of Johnsen score ≥8 tubules equal to 19%. The overall pregnancy rate was 26.6%. In our prospective cohort of patients successful SRR with c-TESE was 47.6%. Lower costs and high reproducibility of this technique still support this procedure as an actual reliable option in NOA patients for sperm retrieval.

Background: Poor ovarian response remains one of the biggest challenges for reproductive endocrinologists. The introduction of corifollitropin alpha (CFA) offered an alternative option to other gonadotropins for its longer halflife, its more rapid achievement of the threshold and higher FSH levels. We compared two different protocols with CFA, a long agonist and a short antagonist, and a no-CFA protocol. Methods: Patients enrolled fulfilled at least two of the followings: AFC < 5, AMH < 1,1 ng/ml, less than three oocytes in a previous cycle, age > 40 years. Ovarian stimulation with an antagonist protocol was performed either with 300 UI rFSH and 150 UI rLH or 300UI HMG. In the long agonist group, after pituitary suppression with triptorelin, CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. In the short antagonist group CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. The primary objective was the effect on the number of oocytes and MII oocytes. Secondary objective were pregnancy rates, ongoing pregnancies and ongoing pregnancies per intention to treat. Results: The use of CFA resulted in a shorter lenght of stimulation and a lower number of suspended treatments. Both the CFA protocols were significantly different from the no-CFA group in the number of retrieved oocytes (p < 0,05), with a non-significant difference in favour of the long agonist protocol. Both CFA groups yielded higher pregnancy rates, especially the long protocol, due to the higher number of oocytes retrieved (p < 0,05), as implantation rates did not differ. The cumulative pregnancy rate was also different, due to the higher number of cryopreserved blastocysts (p < 0,02). Conclusions: The long agonist protocol with the addition of rFSH and rLH showed the best results in all the parameters. A short antagonist protocol with CFA was less effective, but not significantly, although provided better results compared to the no-CFA group. We suggest that a long agonist protocol with CFA and recombinant gonadotropins might be a valuable option for poor responders. Trial registration: The study was approved by the local Ethics Committee (EudraCT2015-002817-31).

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75-150 UI/day were started on day 2-5, GnRH antagonist was added when the lead follicle was >14 mm and the final trigger was obtained with hCG 250 µg or triptorelin 0.2 mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.

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