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The study investigates whether a 3-day pretreatment course with a GnRH antagonist in the early follicular phase has an impact on the number of retrieved COCs in a GnRH antagonist stimulation protocol. This is a retrospective single center crossover study involving women who did not conceive after one GnRH antagonist stimulation cycle ("standard cycle") and proceeded with another GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days ("pretreatment cycle") with fresh embryo transfer or frozen embryo transfer. 430 patients undergoing 860 cycles were included. The mean female age was 34.4 ± 4.8 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%), tubal (4.7) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 430 cycles) and group 2 (pretreatment, 430 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.28). The starting dose of gonadotropin (234.9 vs 196.8 IU, p<0.001), total amount of gonadotropin used (2419 vs 2020 IU, p<0.001), the total number of retrieved COCs (10 vs 7.8 p<0.001) and the number of mature oocytes (8 vs 5.8 p<0.001) were significantly higher in group 2 than in group 1. The Generalized estimating equation (GEE) regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.4, p <0.001 after adjusting for known confounders (age, indication, stimulation dose, type, and duration of stimulation). In conclusion, A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after ovarian stimulation. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C? SUMMARY ANSWER CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C. WHAT IS KNOWN ALREADY Since the beginning of IVF, embryo culture has been performed at 37.0°C; however, the optimal culture temperature remains unknown. Changes in incubator types have led to significant improvements in temperature control. Stable temperature control, i.e. with temperature differences of max. 0.1°C between chambers, is possible in some incubators. A previous prospective pilot study showed that embryo development on Day 5/6 was not affected when embryos were cultured at a stable temperature of 36.6°C or 37.1°C, but culture at 37.1°C resulted in an increased CPR when compared to culture at 36.6°C (74.2% vs 46.4%). STUDY DESIGN, SIZE, DURATION A prospective randomized controlled trial was performed in a tertiary fertility centre between February 2017 and November 26, 2022. A sample size of 89/89 patients with fresh single embryo transfer (SET) was required to achieve 80% power to detect a difference of 0.22 between group proportions (0.43–0.65) at a significance level of 0.05 using a two-sided z -test with continuity correction. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were recruited on the day of oocyte retrieval based on inclusion criteria with final randomization after denudation once six mature oocytes were present. The primary endpoint was CPR (heartbeat at 7 weeks); secondary endpoints were fertilization rate, blastocyst development, biochemical pregnancy rate, live birth rate (LBR), and cumulative live birth rate (CLBR). MAIN RESULTS AND THE ROLE OF CHANCE A total of 304 patients were eligible for the study; of these 268 signed the consent, 234 (intention-to-treat) were randomized and 181 (per-protocol) received a SET on Day 5: 90 received culture at 36.6°C and 91 at 37.1°C. Patients were on average 32.4 ± 3.5 versus 32.5 ± 4.2 years old, respectively. No differences were observed in embryological outcomes per cycle between culture at 36.6°C versus 37.1°C: 12.0 ± 3.8 vs 12.1 ± 3.8 COCs retrieved (P  = 0.88), 10.0 ± 3.1 versus 9.9 ± 2.9 mature oocytes inseminated (P  = 0.68), with a maturation rate of 84.2% (901/1083) versus 83.5% (898/1104) (P  = 0.87); and 8.0 ± 3.1 versus 7.9 ± 2.7 normally fertilized oocytes with a fertilization rate of 79.7% (720/901) vs 80.5% (718/898) (P  = 0.96), respectively. On average 1.5 ± 1.7 versus 1.4 ± 1.9 (P  = 0.25) and 1.1 ± 1.1 versus 0.9 ± 1.0 (P  = 0.45) supernumerary blastocysts were vitrified on Day 5 and Day 6, respectively. The utilization rate per fertilized oocyte was 46.1% vs 41.5% (P  = 0.14). A SET was performed for 181 patients, leading to a biochemical pregnancy rate of 72.2% (65/90) versus 62.7% (57/91) (P  = 0.17), respectively. The CPR per fresh transfer cycle was 51.1% (46/90) versus 48.4% (44/91) [OR (95% CI) 1.11 (0.59–2.08), P  = 0.710]. To date, a CLBR of 73.3% (66/90) versus 67.0% (61/91) (P  = 0.354) has been observed, respectively. In each group, seven patients without live birth have remaining blastocysts frozen. The CPR for the intention-to-treat groups were 38.3% vs 38.6% [OR (95% CI) 0.98 (0.56–1.73), P  = 0.967], respectively, for culture at 36.6°C versus 37.1°C. LIMITATIONS, REASONS FOR CAUTION Only selected patients with expected good prognosis were eligible for the study. WIDER IMPLICATIONS OF THE FINDINGS Embryos tend to tolerate small changes in temperature deviations during culture to the blastocyst stage, as demonstrated by their similar implantation potential at two slightly different temperatures. STUDY FUNDING/COMPETING INTEREST(S) There is no funding or conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03548532. TRIAL REGISTRATION DATE 23 October 2017 DATE OF FIRST PATIENT'S ENROLMENT 10 November 2017 [ABSTRACT FROM AUTHOR]

Research question: Does a frozen-embryo transfer in an artificially-prepared endometrium (FET-HRT) cycle yield similar clinical pregnancy rate with 7 days of oestrogen priming compared to 14 days? Design: This is a single-centre, randomized, controlled, open-label pilot study. All FET-HRT cycles were performed in a tertiary centre between October 2018 and January 2021. Overall, 160 patients were randomized, with a 1:1 allocation, into two groups of 80 patients each: group A (7 days of E2 prior to P4 supplementation) and group B (14 days of E2 prior to P4 supplementation). Both groups received single blastocyst stage embryos on the 6th day of vaginal P4 administration. The primary outcome was the feasibility of such strategy assessed as clinical pregnancy rate, secondary outcomes were biochemical pregnancy rate, miscarriage rate, live birth rate and serum hormone levels on the day of FET. Chemical pregnancy was assessed by an hCG blood test 12 days after FET and clinical pregnancy was confirmed by transvaginal ultrasound at 7 weeks. Results: The analysis included 160 patients who were randomly assigned to either group A or group B on the seventh day of their FET-HRT cycle if the measured endometrial thickness was above 6.5 mm. Following screening failures and of drop-outs, 144 patients were finally included both in group A (75 patients) or group B (69 patients). Demographic characteristics for both groups were comparable. The biochemical pregnancy rate was 42.5% and 48.8% for group A and group B, respectively (p 0.526). Regarding the clinical pregnancy rate at 7 weeks, no statistical difference was observed (36.3% vs 46.3% for group A and group B, respectively, p = 0.261). The secondary outcomes of the study (biochemical pregnancy, miscarriage, and live birth rate) were comparable between the two groups for IIT analysis, as well as the P4 values on the day of FET. Conclusions: In a frozen embryo transfer cycle, performed with artificial preparation of the endometrium, 7 versus 14 days of oestrogen priming are comparable, in terms of clinical pregnancy rate; the advantages of a seven-day protocol include the shorter time to pregnancy, reduced exposure to oestrogens, and more flexibility of scheduling and programming, and less probability to recruit a follicle and have a spontaneous LH surge. It is important to keep in mind that this study was designed as a pilot trial with a limited study population as such it was underpowered to determine the superiority of an intervention over another; larger-scale RCTs are warranted to confirm our preliminary results. Trial registration: Clinical trial number: NCT03930706. [ABSTRACT FROM AUTHOR]

Purpose: Although a robust physiological rationale supports follicle stimulating hormone (FSH) use in male idiopathic infertility, useful biomarkers to evaluate its efficacy are not available. Thus, the primary aim of the study was to evaluate if testosterone serum levels are related to sperm DNA fragmentation (sDF) index change after FSH administration. The secondary aim was to confirm sDF index validity as a biomarker of FSH administration effectiveness in male idiopathic infertility. Methods: A retrospective, post-hoc re-analysis was performed on prospectively collected raw data of clinical trials in which idiopathic infertile men were treated with FSH and both testosterone serum levels and sDF were reported. Results: Three trials were included, accounting for 251 patients. The comprehensive analysis confirmed FSH's beneficial effect on spermatogenesis detected in each trial. Indeed, an overall significant sDF decrease (p < 0.001) of 20.2% of baseline value was detected. Although sDF resulted to be unrelated to testosterone serum levels at baseline, a significant correlation was highlighted after three months of FSH treatment (p = 0.002). Moreover, testosterone serum levels and patients' age significantly correlated with sDF (p = 0.006). Dividing the cohort into responders/not responders to FSH treatment according to sDF change, the FSH effectiveness in terms of sDF improvement was related to testosterone and male age (p = 0.003). Conclusion: Exogenous FSH administration in male idiopathic infertility is efficient in reducing sDF basal levels by about 20%. In terms of sDF reduction, 59.2% of the patients treated were FSH-responders. After three months of FSH administration, a significant inverse correlation between sDF and testosterone was detected, suggesting an association between the FSH-administration-related sDF improvement and testosterone serum levels increase. These observations lead to the hypothesis that FSH may promote communications or interactions between Sertoli cells and Leydig cells. [ABSTRACT FROM AUTHOR]

Do cumulative live birth rates (CLBR) differ between polycystic ovary syndrome (PCOS) phenotypes when a freeze-all strategy is used to prevent OHSS after ovarian stimulation? A single-centre, retrospective cohort study of 422 women with PCOS or polycystic ovarian morphology (PCOM), in whom a freeze-all strategy was applied after GnRH agonist triggering because of hyper-response in their first or second IVF/ICSI. Primary outcome was CLBR; multivariate logistic regression analysis was used. Phenotype A (hyperandrogenism + ovulation disorder + PCOM [HOP]) (n = 91/422 [21.6%]); phenotype C (hyperandrogenism + PCOM [HP]) (33/422 [7.8%]; phenotype D (ovulation disorder + PCOM [OP]) (n = 161/422 [38.2%]); and PCOM (n = 137/422 [32.5%]. Unadjusted CLBR was similar among the groups (69.2%, 69.7%, 79.5% and 67.9%, respectively; P = 0.11). According to multivariate logistic regression analysis, the phenotype did not affect CLBR (OR 0.72, CI 0.24 to 2.14 [phenotype C]; OR 1.55, CI 0.71 to 3.36 [phenotype D]; OR 0.84, CI 0.39 to 1.83 [PCOM]; P = 0.2, with phenotype A as reference). In women with PCOS, hyper-response after ovarian stimulation confers CLBR of around 70%, irrespective of phenotype, when a freeze-all strategy is used. This contrasts with unfavourable clinical outcomes in women with hyperandrogenism and women with PCOS who underwent mild ovarian stimulation targeting normal ovarian response and fresh embryo transfer. The results should be interpreted with caution because the study is retrospective and cannot be generalized to all cycles as they pertain to those in which hyper-response is observed. [ABSTRACT FROM AUTHOR]

Are cumulative live birth rates (CLBR) after follitropin alpha (Ovaleap®) and follitropin beta (Puregon®) similar when used for ovarian stimulation with ICSI (intracytoplasmic sperm injection) in a first-rank gonadotrophin-releasing hormone (GnRH) antagonist protocol? Retrospective single-centre cohort study including 832 infertile patients undergoing ovarian stimulation with a daily dose of 150–225 IU FSH in their first ICSI cycle at a tertiary referral centre between July 2016 and July 2019. Of those, 349 patients used Ovaleap and 483 patients received Puregon. Baseline characteristics were not statistically different between the groups. The duration of stimulation was slightly longer in the Ovaleap group (10.6 ± 1.7 versus 10.3 ± 1.6 days; P = 0.012). The number of mature oocytes was not statistically different and there was no significant difference in fertilization rate or embryo utilization rate between the two groups. After fresh embryo transfer, biochemical pregnancy rate (137/349 [39.3%] versus 186/483 [38.5%]) as well as clinical pregnancy rate (105/349 [30.1%] versus 152/483 [31.5%]) were comparable (P = 0.83 and 0.67, respectively). Live birth rate (LBR) after fresh embryo transfer (94/349 [26.9%] versus 141/483 [29.2%]; P = 0.48) and CLBR (199/349 [57.0%] versus 287/483 [59.4%]; P = 0.49) were not significantly different. Multivariable regression analysis revealed that the type of gonadotrophin was not associated with CLBR (P = 0.28). This retrospective study shows no significant difference in CLBR between Ovaleap and Puregon in patients undergoing their first GnRH antagonist ICSI cycle. [ABSTRACT FROM AUTHOR]

Over 80 species are recognized in the commercially important genus Morchella, many of them endemic to specific regions or continents. Among them, M. anatolica and M. rufobrunnea are the earliest diverging lineages and are key in decoding the evolutionary history, global biogeography, and ecological trends within this iconic genus. Early ancestral area reconstruction (AAR) tests postulated a western North American origin of morels but had not included in the analyses M. anatolica, whose phylogenetic identity remained at the time unresolved. Following new collections of M. anatolica and M. rufobrunnea from the Mediterranean islands of Cyprus, Kefalonia, Lesvos, Malta, and Zakynthos, we performed revised AAR tests to update the historical biogeography of the genus. Our results, inferred from multilocus analysis of an expanded data set of 79 phylospecies, challenge previous reconstructions and designate the Mediterranean basin as the most likely place of origin for morels. Detailed morphoanatomical analyses demonstrate that ascocarp rufescence, the nondarkening apothecial ridges, the absence of a sinus, and the stipe pruinescence are all stable synapomorphic features of sect. Rufobrunnea, which could be interpreted as ancestral for the genus. The saprotrophic mode of nutrition, suggested by the prolific in vitro growth of M. anatolica, might also be an ancestral trait. Emended descriptions, including extensive imagery and scanning electron microscopy, are provided, and a new evolutionary hypothesis of the genus is proposed. [ABSTRACT FROM AUTHOR]

What are the reproductive outcomes of women aged 43 years and older undergoing IVF and intracytoplasmic sperm injection (ICSI) treatment using their own eggs. Retrospective study of 833 woman aged 43 years or older undergoing their first IVF and ICSI cycle using autologous oocytes at a tertiary referral hospital between January 1995 and December 2019. Live birth rate (LBR) after 24 weeks' gestation was the primary outcome. Ninety-five out of 833 (11.4%) had a positive HCG, whereas 59 (62.1% per positive HCG) had a miscarriage before 12 weeks' gestation and 36 (4.3%) live births were achieved. Analysis by age showed that the number of cumulus–oocyte complexes retrieved was significantly different between the four age groups: 43 years (5 [3–9]); 44 years (5 [2–7]); 45 years (3 [2–8)]); ≥45 years (2.5 [2–6]); P < 0.01; the number of metaphase II oocytes, however, was similar. Positive HCG rates remained low: 43 years (78/580 [13.4%]); 44 years (14/192 [7.3%]); 45 years (1/39 [2.6%]; and ≥46 years (2/22 [9.1%]); P = 0.03, as did LBR: 43 years (28 [4.8%]); 44 (7 [3.6%]); 45 years (0 [0%]); and ≥46 years (1 [4.5%]); P = 0.5. Multivariate regression analysis revealed that only number of metaphase II was significantly associated with LBR, when age was considered as a continuous (OR 1.08, 96% CI 1.004 to 1.16) or categorical variable (OR 1.08, 95% CI 1.005 to 1.16). The chances of achieving a live birth in patients aged 43 years and older undergoing IVF/ICSI with their own gametes are low, even in cases of patients with a relatively 'normal' ovarian reserve for their age. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are cumulative and live birth rates (LBRs) comparable in poor ovarian response women treated with different protocols of mild stimulation IVF (i.e. oral compounds, lower doses or shorter treatments) versus conventional IVF? SUMMARY ANSWER Mild ovarian stimulation (MOS) results in comparable outcomes to those of conventional stimulation in poor ovarian response patients with low ovarian reserve. WHAT IS KNOWN ALREADY Several randomized trials and meta-analyses have been published evaluating the role of mild (MOS) versus conventional ovarian stimulation in poor ovarian response patients. Most report a potentially higher safety profile, patient satisfaction and lower costs, suggesting that the higher cycle cancellation rate and fewer oocytes retrieved following MOS does not affect the final reproductive outcome. Additionally, over the last few years, new publications have added data regarding MOS, and shown the possible benefit of a higher oocyte yield which may also improve prognosis in patients with poor ovarian response. STUDY DESIGN, SIZE, DURATION We conducted a systematic search of relevant randomized controlled trials (RCTs). We searched electronic databases, including MEDLINE, EMBASE, LILACS-BIREME, CINAHL, The Cochrane Library, CENTRAL (Cochrane Register), Web of Science, Scopus, Trip Database and Open Grey, to identify all relevant studies published up to March 2020. We examined trial registries for ongoing trials. No publication-year or language restrictions were adopted. We explored the reference list of all included studies, reviews and abstracts of major scientific meetings. The primary outcomes were cumulative and fresh LBR (CLBR and FLBR) per woman randomized. PARTICIPANTS/MATERIALS, SETTING, METHODS We included subfertile women undergoing IVF/ICSI characterized as poor responders and compared primary and secondary outcomes between the different protocols of mild stimulation IVF (i.e. oral compounds, lower doses or shorter treatments) and conventional IVF. We used the PICO (Patients, Intervention, Comparison and Outcomes) model to select our study population. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 15 RCTs were included in the meta-analysis. CLBR and FLBR were comparable between mild versus conventional stimulation (RR 1.15; 95% CI: 0.73 − 1.81; I2 = 0%, n = 424, moderate certainty and RR 1.01; 95% CI: 0.97 − 1.04; I 2 = 0%, n = 1001, low certainty, respectively). No difference was observed either when utilizing oral compounds (i.e. letrozole and clomiphene) or lower doses. Similarly, ongoing pregnancy rate (OPR) and clinical pregnancy rate (CPR) were equivalent when comparing the two groups (RR 1.01; 95% CI: 0.98 − 1.05; I 2 = 0%, n = 1480, low certainty, and RR 1.00; 95% CI: 0.97 − 1.03; I2 = 0%, n = 2355, low certainty, respectively). A significantly lower oocyte yield (mean differences (MD) −0.80; 95% CI: −1.28, -0.32; I2 = 83%, n = 2516, very low certainty) and higher rate of cycle cancellation (RR 1.48; 95% CI: 1.08 − 2.02; I2 = 62%, n = 2588, low certainty) was observed in the MOS group. LIMITATIONS, REASONS FOR CAUTION The overall quality of the included studies was low to moderate. Even though strict inclusion criteria were used, the selected studies were heterogeneous in population characteristics and treatment protocols. We found no differences in CLBR between MOS and COS (95% CI: 0.73 − 1.81.) WIDER IMPLICATIONS OF THE FINDINGS MOS could be considered as a treatment option in low prognosis poor responder patients, given that it results in similar fresh and CLBRs compared with COS. A milder approach is associated with a lower number of oocytes retrieved and a higher cancellation rate, although treatment cost is significantly reduced. Future research should focus on which type of ovarian stimulation may be of benefit in better prognosis women. WHAT DOES THIS MEAN FOR PATIENTS? The objective of this study was to examine whether a lower (mild stimulation) or higher (conventional stimulation) dose used during ovarian stimulation makes a difference to the chances of a successful outcome (i.e. live birth, pregnancy) in women with a low ovarian reserve (also named 'poor responders') undergoing IVF. For many years, there has been a debate on whether poor responders would benefit from a mild ovarian stimulation regimen (i.e. lower doses, the use of an oral medication (letrozole or clomiphene) or delaying the start of the treatment) compared with conventional stimulation (higher doses to obtain more oocytes and consequently more embryos), with studies yielding conflicting results. We performed a systematic review (i.e. literature review that uses systematic methods to collect data) and a meta-analysis (i.e. a statistical analysis that combines the results of multiple scientific studies) to evaluate whether one strategy was superior to the other. Based on our study, mild stimulation could be considered as an option for women with poor ovarian reserve, as we found similar results between the two strategies. STUDY FUNDING/COMPETING INTERESTS There were no sources of financial support. N.P.P. received research grants, honoraria for lectures from: Merck Serono, MSD, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex and Gedeon Richter. P.D. received unrestricted grants and honoraria from Merck Serono, MSD and Ferring Pharmaceuticals. I.G.F. received unrestricted grants and honoraria from Merck Serono, MSD, Ferring Pharmaceuticals, Gedeon-Richter and IBSA. P.M.B. reported no conflict of interest. TRIAL REGISTRATION NUMBER CRD42020167260. [ABSTRACT FROM AUTHOR]

36.9% of men worldwide use tobacco. Previous studies suggest a negative effect of cigarette smoking on semen quality, but the results are contradictory. We have studied the effects of smoking on the semen characteristics such as sperm concentration, semen volume, sperm motility, sperm vitality and sperm morphology in a large group of infertile men. This retrospective study was conducted on a total of 5146 infertile men with at least one year of idiopathic infertility, who admitted to the Centre for Reproductive medicine (CRG) at the Brussels University Hospital, Belgium between 2010 and 2017. The smokers were classified as mild (1-10 cigarettes/d), moderate (11-20 cigarettes/d) or heavy smokers (> 20 cigarettes/d). Semen analysis was performed for all patients. Statistical analysis was performed using the R software package and t-test or Mann-Whitney U tests were used, group comparisons were performed using ANOVA, ANCOVA or Kruskal-Wallis tests as appropriate. A p-value <0.05 was considered as statistically significant. Comparing the semen parameters in the two global groups showed that smoking had a significant decrease in semen volume (p=0.04074) and sperm concentration (p=0.029). ANOVA testing on the different smoking groups versus non-smoking group showed a significant decrease in sperm concentration (p=0.0364). After adjusting for the confounders, age and testosterone, ANCOVA testing showed significant effect on the sperm concentration (p=0.03871) in smokers versus non-smokers. No significant correlation was detected between the other semen characteristics. We concluded that smoking had a significant and independent effect on the sperm concentration in a semen analysis. Other parameters, like semen volume, sperm motility, sperm vitality and sperm morphology were not influenced by smoking. [ABSTRACT FROM AUTHOR]

Study Question: Does the freeze-all strategy in high-responders increase pregnancy rates and improve safety outcomes when compared with GnRH agonist triggering followed by low-dose hCG intensified luteal support with a fresh embryo transfer?Summary Answer: Pregnancy rates after either fresh embryo transfer with intensified luteal phase support using low-dose hCG or the freeze-all strategy did not vary significantly; however, moderate-to-severe ovarian hyperstimulation syndrome (OHSS) occurred more frequently in the women who attempted a fresh embryo transfer.What Is Known Already: Two strategies following GnRH agonist triggering (the freeze-all approach and a fresh embryo transfer attempt using a low-dose of hCG for intensified luteal phase support) are safer alternatives when compared with conventional hCG triggering with similar pregnancy outcomes. However, these two strategies have never been compared head-to-head in an unrestricted predicted hyper-responder population.Study Design, Size, Duration: This study included women with an excessive response to ovarian stimulation (≥18 follicles measuring ≥11 mm) undergoing IVF/ICSI in a GnRH antagonist suppressed cycle between 2014 and 2017. Our primary outcome was clinical pregnancy at 7 weeks after the first embryo transfer. Secondary outcomes included live birth and the development of moderate-to-severe OHSS.Participants/materials, Setting, Methods: Following GnRH agonist triggering, women were randomized either to cryopreserve all good-quality embryos followed by a frozen embryo transfer in an subsequent artificial cycle or to perform a fresh embryo transfer with intensified luteal phase support (1500 IU hCG on the day of oocyte retrieval, plus oral estradiol 2 mg two times a day, plus 200 mg of micronized vaginal progesterone three times a day).Main Results and the Role Of Chance: A total of 212 patients (106 in each arm) were recruited in the study, with three patients (one in the fresh embryo transfer group and two in the freeze-all group) later withdrawing their consent to participate in the study. One patient in the freeze-all group became pregnant naturally (clinical pregnancy diagnosed 38 days after randomization) prior to the first frozen embryo transfer. The study arms did not vary significantly in terms of the number of oocytes retrieved and embryos produced/transferred. The intention to treat clinical pregnancy and live birth rates (with the latter excluding four cases lost to follow-up: one in the fresh transfer and three in the freeze-all arms, respectively) after the first embryo transfer did not vary significantly among the fresh embryo transfer and freeze-all study arms: 51/105 (48.6%) versus 57/104 (54.8%) and 41/104 (39.4%) versus 42/101 (41.6%), respectively (relative risk for clinical pregnancy 1.13, 95% CI 0.87-1.47; P = 0.41). However, moderate-to-severe OHSS occurred solely in the group that received low-dose hCG (9/105, 8.6%, 95% CI 3.2% to 13.9% vs 0/104, 95% CI 0 to 3.7, P < 0.01).Limitations, Reasons For Caution: The sample size calculation was based on a 19% absolute difference in terms of clinical pregnancy rates, therefore smaller differences, as observed in the trial, cannot be reliably excluded as non-significant.Wider Implications Of the Findings: This study offers the first comparative analysis of two common strategies applied to women performing IVF/ICSI with a high risk to develop OHSS. While pregnancy rates did not vary significantly, a fresh embryo transfer with intensified luteal phase support may still not avoid the risk of moderate-to-severe OHSS and serious consideration should be made before recommending it as a routine first-line treatment. Future trials may allow us to confirm these findings.Study Funding/competing Interest(s): The authors have no conflicts of interest to disclose. No external funding was obtained for this study.Trial Registration Number: ClinicalTrials.gov identifier NCT02148393.Trial Registration Date: 28 May 2014.Date Of First Patient’s Enrolment: 30 May 2014. [ABSTRACT FROM AUTHOR]

Study Question: Does the phenotype of patients with polycystic ovary syndrome (PCOS) affect clinical outcomes of ART following in-vitro oocyte maturation?Summary Answer: Cumulative live birth rates (CLBRs) after IVM were significantly different between distinct PCOS phenotypes, with the highest CLBR observed in patients with phenotype A/HOP (= hyperandrogenism + ovulatory disorder + polycystic ovaries), while IVM in patients with phenotype C/HP (hyperandrogenism + polycystic ovaries) or D/OP (ovulatory disorder + polycystic ovaries) resulted in lower CLBRs (OR 0.26 (CI 0.06-1.05) and OR 0.47 (CI 0.25-0.88), respectively, P = 0.03).What Is Known Already: CLBRs in women with hyperandrogenic PCOS phenotypes (A/HOP and C/HP) have been reported to be lower after ovarian stimulation (OS) and ART when compared to CLBR in women with a normo-androgenic PCOS phenotype (D/OP) and non-PCOS patients with a PCO-like ovarian morphology (PCOM). Whether there is an influence of the different PCOS phenotypes on success rates of IVM has been unknown.Study Design, Size, Duration: This was a single-centre, retrospective cohort study including 320 unique PCOS patients performing their first IVM cycle between April 2014 and January 2018 in a tertiary referral hospital.Participants/materials, Setting, Methods: Baseline patient characteristics and IVM treatment cycle data were collected. The clinical outcomes following the first IVM embryo transfer were retrieved, including the CLBR defined as the number of deliveries with at least one live birth resulting from one IVM cycle and all appended cycles in which fresh or frozen embryos were transferred until a live birth occurred or until all embryos were used. The latter was considered as the primary outcome. A multivariate regression model was developed to identify prognostic factors for CLBR and test the impact of the patient's PCOS phenotype.Main Results and the Role Of Chance: Half of the patients presented with a hyperandrogenic PCOS phenotype (n = 140 A/HOP and n = 20 C/HP vs. n = 160 D/OP). BMI was significantly different between phenotype groups (27.4 ± 5.4 kg/m2 for A/HOP, 27.1 ± 5.4 kg/m2 for C/HP and 23.3 ± 4.4 kg/m2 for D/OP, P < 0.001). Metformin was used in 33.6% of patients with PCOS phenotype A/HOP, in 15.0% of C/HP patients and in 11.2% of D/OP patients (P < 0.001). Anti-müllerian hormone levels differed significantly between groups: 12.4 ± 8.3 µg/l in A/HOP, 7.7 ± 3.1 µg/l in C/HP and 10.4 ± 5.9 µg/l in D/OP patients (P = 0.01). The number of cumulus-oocyte complexes (COC) was significantly different between phenotype groups: 25.9 ± 19.1 COC in patients with phenotype A/HOP, 18.3 ± 9.0 COC in C/HP and 19.8 ± 13.5 COC in D/OP (P = 0.004). After IVM, patients with different phenotypes also had a significantly different number of mature oocytes (12.4 ± 9.3 for A/HOP vs. 6.5 ± 4.2 for C/HP vs. 9.1 ± 6.9 for D/OP, P < 0.001). The fertilisation rate, the number of usable embryos and the number of cycles with no embryo available for transfer were comparable between the three groups. Following the first embryo transfer, the positive hCG rate and LBR were comparable between the patient groups (44.7% (55/123) for A/HOP, 40.0% (6/15) for C/HP, 36.7% (47/128) for D/OP, P = 0.56 and 25.2% (31/123) for A/HOP, 6.2% (1/15) for C/HP, 26.6% (34/128) for D/OP, respectively, P = 0.22). However, the incidence of early pregnancy loss was significantly different across phenotype groups (19.5% (24/123) for A/HOP, 26.7% (4/15) for C/HP and 10.2% (13/128) for D/OP, P = 0.04). The CLBR was not significantly different following univariate analysis (40.0% (56/140) for A/HOP, 15% (3/20) for C/HP and 33.1% (53/160) for D/OP (P = 0.07)). When a multivariable logistic regression model was developed to account for confounding factors, the PCOS phenotype appeared to be significantly correlated with CLBR, with a more favourable CLBR in the A/HOP subgroup (OR 0.26 for phenotype C/HP (CI 0.06-1.05) and OR 0.47 for phenotype D/OP (CI 0.25-0.88), P = 0.03)).Limitations, Reasons For Caution: These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors and misassignment of the PCOS phenotype. Moreover, the sample size for phenotype C/HP was too small to draw conclusions for this subgroup of patients.Wider Implications Of the Findings: Caucasian infertile patients with a PCOS phenotype A/HOP who undergo IVM achieved a higher CLBR than their counterparts with C/HP and D/OP. This is in strong contrast with previously reported outcomes following OS where women with PCOS and hyperandrogenism (A/HOP and C/HP) performed significantly worse. For PCOS patients who require ART, the strategy of OS followed by an elective freeze-all strategy remains to be compared with IVM in a prospective fashion; however, the current data provide support for IVM as a valid treatment option, especially in the most severe PCOS phenotypes (A/HOP). Our data suggest that proper patient selection is of utmost importance in an IVM programme.Study Funding/competing Interest(s): The clinical IVM research has been supported by research grants from Cook Medical and Besins Healthcare. All authors declared no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

The prolonged lockdown of health services providing high-complexity fertility treatments –as currently recommended by many reproductive medicine entities– is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born –but who will not be so due to the lockdown of infertility services– might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment. [ABSTRACT FROM AUTHOR]

Research Question: Does reproductive outcome differ among the various subgroups of poor ovarian responders according to the Bologna criteria? Design: This was a retrospective, cohort study including poor ovarian responders according to Bologna criteria, undergoing an ICSI cycle from January 2011 until December 2017. Patients were divided into four groups: (1) age ≥ 40 years and abnormal ovarian response test, (2) age ≥ 40 years, abnormal ovarian reserve test and one previous poor response to stimulation, (3) age ≥ 40 years and one previous poor response, (4) abnormal ovarian reserve test and one previous poor response. Result(s): Overall, 846 cycles in 706 Bologna poor ovarian responders were included: 310 cycles in group 1, 169 in group 2, 52 in group 3, and 315 in group 4. There were significant differences in age, antral follicle count, antimüllerian hormone, cycle cancellation rates, and number of retrieved oocytes between the four groups. Live birth and cumulative live birth rate differed significantly between groups and were highest in Group 4 [Live birth rate: 7.4% (1) vs. 4.1% (2) vs. 5.8% (3) vs. 13.4% (4), p = 0.001 and Cumulative live birth rate: 8.3% (1) vs. 4.1 % (2) vs. 9.6% (3) vs. 16.8% (4) p < 0.001]. The multivariate GEE analysis revealed that the number of MIIs and the Bologna criteria pattern were the variables which were significantly associated with cumulative live birth rate. Conclusion(s): Poor ovarian responders represent a heterogeneous population. The young subpopulation has a better clinical prognosis in terms of fresh and cumulative live birth rate. [ABSTRACT FROM AUTHOR]

Monitoring the riverine output of Suspended Particulate Matter (SPM) distribution in marine embayment is a crucial factor for the water quality of neighbouring coastal regions. This study presents satellite-derived SPM calculations against in-situ measurements in the continental shelf of North-East Aegean surrounding the transboundary Evros river mouth. Surface SPM, Inherent Optical Properties (IOPs) and remote sensing reflectance (Rrs) data were collected in a field campaign during low river discharge period (June 2016). The relationship between the optical backscattering coefficient (bbp) and the in-situ SPM concentrations was investigated. Subsequently, an empirical single band model was applied for estimating SPM concentrations by using the Landsat-8 Operational Land Imager (L8/OLI) red band and the model was then locally tuned within the study area. Furthermore, a multi-band SPM-retrieval algorithm was developed using the in-situ surface reflectance Rrs for calibration and it was validated using the Leave-One-Out Cross Validation technique (LOOCV). The relationship between in-situ SPM and backscattering coefficient values showed good proportionality, thus, nominating the predominance of terrestrial mineral particles. Validation against field measurements indicated that the SPM concentrations derived from the newly-developed multi-band algorithm had an improved significance correlation (96%), compared to both the single band model (not-tuned) (coefficient of determination, R2 = 0.82) and its locally tuned version (R2 = 0.83). Most importantly, the generated multi-band model apart from exhibiting the best performance (R2 = 0.93), it revealed high SPM spots which were not detected by the locally tuned single band model, indicating additional processes originating from river outflows, coastal erosion and subaqueous thermal springs in the area. In contrast, the locally tuned single band model overestimated SPM values in offshore waters, where low concentrations are encountered under the influence of the clear Black Sea Water (BSW). [ABSTRACT FROM AUTHOR]

Do ongoing pregnancy rates (OPR) differ between modified natural cycle IVF (MNC-IVF) and conventional high-dose ovarian stimulation (HDOS) in advanced-age Bologna poor responders? This was a retrospective cohort study including patients with poor ovarian response (POR) attending a tertiary referral university hospital from 1 January 2011 to 1 March 2017. All women who fulfilled the Bologna criteria for POR and aged ≥40 years who underwent their first intracytoplasmic sperm injection (ICSI) cycle in the study centre were included. In total, 476 advanced-age Bologna poor responder patients were included in the study: 189 in the MNC-IVF group and 287 in the HDOS group. OPR per patient were significantly lower in the MNC-IVF group (5/189, 2.6%) compared with the HDOS group (29/287, 10.1%) (P = 0.002). However, after adjustment for relevant confounders (number of oocytes and presence of at least one top-quality embryo), the multivariate logistic regression analysis showed that the type of treatment strategy (HDOS versus MNC-IVF) was not significantly associated with OPR (odds ratio 2.56, 95% confidence interval 0.9–7.6). In advanced-age Bologna poor responders, MNC-IVF, which is a more patient-friendly approach, could be a reasonable alternative in this difficult-to-treat group of women. [ABSTRACT FROM AUTHOR]