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Research Question: Does a short co-incubation of gametes in conventional IVF affect post-insemination outcomes and embryo morphokinetics?, Design: Sibling oocyte randomized pilot study conducted between December 2020 and March 2023. Eligible couples (n = 55) were women aged 18-43 years with BMI 35 km/m 2 or lower and male normal semen parameters. Cumulus oocyte complexes (COC) (six to 12) were randomized in a 1:1:2 proportion in long (16-18 h) or short (2 h) co-incubation IVF exposure and ICSI, respectively. All oocytes inseminated via IVF were monitored by time-lapse. Blastocysts graded BL3CC or higher underwent trophectoderm biopsy on days 5, 6 or 7, and were analysed by next-generation sequencing., Results: A total of 954 COC were distributed to long co-incubation (n = 235 [24.6%]), short co-incubation (n = 235 [24.6%]) and ICSI (n = 484 [50.7%]). In total, 202 were MII after long co-incubation, 209 after short co-incubation and 394 at ICSI. Regression analyses showed that short co-incubation groups (OR 0.72, 95% CI 0.46 to 1.11, P = 0.139) and ICSI (OR 1.43, 95% CI 0.95 to 2.15, P = 0.090) did not significantly affect normal fertilization rates (2PN) compared with long co-incubation. Usable blastocysts per MII, per 2PN, and euploid blastocysts per MII, per 2PN and per tested blastocysts were similar among the groups. The rate of embryo arrest (hazard ratio [HR] 0.79, 95% CI 0.57 to 1.11, P = 0.183) and timings to reach morphokinetic milestones among embryos reaching blastulation were similar between IVF groups (P > 0.05 for all)., Conclusion: A short 2-h co-incubation of gametes in IVF yields comparable fertilization, blastocyst and euploidy rates without adverse embryo morphokinetic events, compared with standard overnight co-incubation., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is late follicular phase stimulation as efficient as early follicular phase stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol in oocyte donors in terms of the number of oocytes., Design: In this open label, phase 3, non-inferiority, randomized controlled trial using a two-arm design with a 1:1 allocation ratio, 84 oocyte donors were allocated to the early follicular start group (control group, n = 41) or the late follicular start group (study group, n = 43). In the control group, women followed a fixed GnRH antagonist protocol with recombinant FSH (r-FSH) 225 IU. In the study group, r-FSH 225 IU was initiated in the late follicular phase. The primary outcome was the number of oocytes. The secondary outcomes were the number of mature oocytes, consumption of gonadotrophins and GnRH antagonist, and cost of medication., Results: The number of oocytes did not differ between the control group and the study group (intent-to-treat analysis 15.5 ± 11.0 versus 14.0 ± 10.7, P = 0.52; per-protocol analysis 18.2 ± 9.7 versus 18.8 ± 7.8, P = 0.62). In addition, the number of mature oocytes did not differ between the groups (14.1 ± 8.1 versus 12.7 ± 8.5, P = 0.48). The duration of stimulation was shorter in the control group (10.0 ± 1.4 versus 10.9 ± 1.5 days, P = 0.01). The total amount of r-FSH used was lower in the control group (2240.7 ± 313.9 IU versus 2453.9 ± 330.1 IU, P = 0.008). A GnRH antagonist was used for approximately 6 days in the control group, while a GnRH antagonist was only prescribed for one woman in the study group (6.0 ± 1.4 days versus 0.13±0.7 days, P < 0.001). There was a significant difference in the cost of medication per cycle between the groups (1147.9 ± 182.8€ in control group versus 979.9 ± 129.0€ in study group, P < 0.001)., Conclusions: Late follicular phase stimulation is as efficient as early follicular phase stimulation in terms of the number of oocytes., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does a progestin-primed ovarian stimulation (PPOS) protocol with dydrogesterone from cycle day 7 yield similar outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol in the same oocyte donors?, Design: This retrospective longitudinal study included 128 cycles from 64 oocyte donors. All oocyte donors had the same type of gonadotrophin and daily dose in both stimulation cycles. The primary outcome was the number of cumulus-oocyte complexes (COC) retrieved., Results: The number of COC retrieved (mean ± SD 19.7 ± 10.8 versus 19.2 ± 8.3; P = 0.5) and the number of metaphase II oocytes (15.5 ± 8.4 versus 16.2 ± 7.0; P = 0.19) were similar for the PPOS and GnRH antagonist protocols, respectively. The duration of stimulation (10.5 ± 1.5 days versus 10.8 ± 1.5 days; P = 0.14) and consumption of gonadotrophins (2271.9 ± 429.7 IU versus 2321.5 ± 403.4 IU; P = 0.2) were also comparable, without any cases of premature ovulation. Nevertheless, there was a significant difference in the total cost of medication per cycle: €898.3 ± 169.9 for the PPOS protocol versus €1196.4 ± 207.5 (P < 0.001) for the GnRH antagonist protocol., Conclusion: The number of oocytes retrieved and number of metaphase II oocytes were comparable in both stimulation protocols, with the advantage of significant cost reduction in favour of the PPOS protocol compared with the GnRH antagonist protocol. No cases of premature ovulation were observed, even when progestin was started later in the stimulation., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The growing utilization of assisted reproductive technology (ART) by the LGBTQ+ community, especially among lesbian couples, challenges societal norms and promotes inclusivity. The reception of oocytes from partner (ROPA) technique enables both female partners to have a biological connection to their child. A systematic review was conducted of the literature on ROPA IVF to provide the latest data and a SWOT analysis was subsequently performed to understand the strengths, weaknesses, opportunities and threats associated with ROPA IVF. Publications from 2000 to 2023 with relevant keywords were reviewed and 16 records were included. Five studies provided clinical information on couples who used ROPA IVF. ROPA IVF provides a unique opportunity for a biological connection between the child and both female partners and addresses concerns related to oocyte donation and anonymity. Weaknesses include limited cost-effectiveness data and unresolved practical implications. Opportunities lie in involving both partners in parenthood, advancing ART success rates and mitigating risks. Threats encompass increased pregnancy complications, ethical concerns, insufficient safety data, legal or cultural barriers, and emotional stress. In conclusion, ROPA IVF offers a promising solution for lesbian couples seeking to create a family in which both partners want to establish a biological connection with their child., (Copyright © 2023 Reproductive Healthcare Ltd. All rights reserved.)

Research Question: What is the intra-day variation of serum progesterone related to vaginal progesterone administration on the day of frozen embryo transfer (FET) in an artificial cycle?, Design: A prospective cohort study was conducted including 22 patients undergoing a single blastocyst artificial cycle (AC)-FET from August to December 2022. Endometrial preparation was achieved by administering oestradiol valerate (2 mg three times daily) and consecutively micronized vaginal progesterone (MVP; 400 mg twice daily). A blastocyst FET was performed on the 6th day of MVP administration. Serum progesterone concentrations were measured on the day of transfer at 08:00, 12:00, 16:00 and 20:00 hours. The first and last blood samples were collected just before MVP was administered., Results: The mean age and body mass index of the study population were 33.95 ± 3.98 years and 23.10 ± 1.95 kg/m 2 . The mean P-values at 08:00, 12:00, 16:00 and 20:00 hours were 11.72 ± 4.99, 13.59 ± 6.33, 10.23 ± 3.81 and 9.28 ± 3.09 ng/ml, respectively. A significant decline, of 2.41 ng/ml (95% confidence interval 0.81-4.00), was found between the first and last progesterone measurements., Conclusion: A statistically significant intra-day variation of serum progesterone concentrations on the day of FET in artificially prepared cycles was observed. This highlights the importance of a standardized procedure for the timing of progesterone measurement on the day of AC-FET. Of note, the study results are applicable only to women using MVP for luteal phase support; therefore it is necessary to confirm its validity in comparison with the different existing administration routes of progesterone., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is parental consanguinity associated with a reduced ovarian reserve in women from the Arabian Peninsula, comparing anti-Müllerian hormone (AMH) and antral follicle count (AFC)?, Design: Retrospective large-scale observational study including 2482 women from the Arabian Peninsula, aged 19-49 years, who had their serum AMH and AFC measured as part of their fertility assessment, from May 2015 to November 2019. Consanguinity was defined as women whose parents were first-degree or second-degree cousins. Serum AMH was measured for all participants., Results: A total of 2198 women were included: 605 in the consanguine group (27.53%), 1593 (72.47%) in the non-consanguine group. There were no significant differences between groups in terms of body mass index, years of infertility or smoking status. Women from the consanguine group were significantly younger (mean age 33.74 ± 6.64 years) compared with the non-consanguine group (mean age 34.78 ± 6.64 years, P < 0.0001). Median AMH and AFC for the consanguine group were 1.90 ng/ml (min-max: 0.01-23.8) and 11 (0-80), respectively, and for the non-consanguine group 1.84 ng/ml (min-max: 0.01-23.0) and 11 (0-60), respectively. AMH and AFC exhibit an age-dependent decline. As both parameters are age-dependent, the multivariate analysis showed that women from the consanguine group presented significantly lower AMH (coefficient of variation [CV] -0.07 ± 0.03, P = 0.036) and AFC (CV -0.16 ± 0.06, P = 0.003) compared with non-consanguine women, and the highest differences were found for women below 35 years of age (AMH median [min-max]: 2.82 ng/ml (0.01-23.80) versus 2.92 ng/ml (0.01-23.00); P = 0.035; AFC median [min-max]: 15 (0-80) versus 14 (0-80); P = 0.001)., Conclusion: The adjusted analysis by age indicates that female parental consanguinity is associated with reduced ovarian reserve in the studied population. Clinical evaluation should include extensive family history and subsequent counselling of the affected couples., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does the position of the euploid blastocyst in the uterine cavity upon transfer, measured as distance in millimetres (mm) from the fundus (DFF) to the air bubble, influence implantation potential?, Design: A total of 507 single/double euploid frozen embryo transfer (FET) cycles at blastocyst stage were included retrospectively between March 2017 and November 2018 at a single centre. The patients were on average 33.3 years old. The FET were performed in natural cycles (n = 151) or hormone replacement therapy cycles (n = 356)., Results: Of the 507 transfers, 370 (73.0%) resulted in a pregnancy, defined as human chorionic gonadotrophin concentration over 15 mIU/ml, and 341 (67.3%) in a clinical pregnancy, with an implantation rate of 62.0% and ongoing pregnancy rate of 59.6% (302/507). When comparing the number of embryos transferred, the pregnancy rate, clinical pregnancy rate and ongoing pregnancy rate were significantly higher after double-embryo transfer (DET) (P = 0.002: P < 0.001 and P = 0.002). The quality of the blastocyst in the single-embryo transfer group had a positive effect on the pregnancy rate (A versus B, P = 0.016; A versus C, P = 0.003) and clinical pregnancy rate (A versus C, P = 0.013). After performing a multivariate logistic regression analysis to consider the effect of all explanatory variables, a negative effect between DFF and pregnancy (P = 0.001), clinical pregnancy (P = 0.001) and ongoing pregnancy (P = 0.030) was found. When all variables remained constant, an increase of 1 mm of DFF changed the odds of pregnancy by 0.882, of clinical pregnancy by 0.891 and of ongoing pregnancy by 0.925. No significant effect of DFF was found on the miscarriage outcome (P = 0.089)., Conclusions: The depth of blastocyst replacement inside the uterine cavity may influence the pregnancy, clinical pregnancy and ongoing pregnancy rates and should be considered as an important factor to improve the success of IVF cycles., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: This study explored the relationship between anti-Müllerian hormone (AMH) and oocyte survival after vitrification. The association between AMH and blastocyst formation after oocyte vitrification was also assessed., Design: A retrospective observational analysis was performed in a private IVF centre. A total of 4507 metaphase-II warmed oocytes were included from 450 couples, predominantly of Arab ethnicity. Between August 2015 and August 2018, couples underwent 484 intracytoplasmic sperm injection (ICSI) treatments using vitrified-warmed oocytes., Results: Patients' median age ± SD was 36.2 ± 6.1 years, AMH concentration 2.6 ± 3.4 ng/ml and body mass index (BMI) 26.5 ± 4.6 kg/m 2 . The oocyte survival rate after vitrification was 87.37 ± 20.42%. AMH concentration showed a significant correlation (Kendall's tau 0.087, P = 0.0079) with oocyte survival rate independent of oocyte yield. Correlation was significant (odds ratio 1.041, 95% confidence interval 1.007-1.077, P = 0.018) when a multivariant model was applied that included AMH, age and BMI. The receiver operating characteristic curve showed an AMH cut-off value of 1.09 ng/ml that could obtain at least a 70% survival rate, with an area under the curve of 0.669. Regarding embryo development in ICSI cycles including fresh and warmed oocytes for the same patient, blastocyst formation rate was higher in fresh compared with warmed oocytes (P < 0.001). In this subgroup no significant correlation was seen between fertilization or blastocyst rate and AMH concentration., Conclusions: AMH concentration showed a significant correlation with oocyte survival. Blastocyst formation was significantly lower after oocyte vitrification, but no correlation was found with AMH. Clinicians should carefully evaluate oocyte vitrification for patients with AMH below 1.09 ng/ml and consider embryo accumulation for these patients in preference to oocyte accumulation., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the current reproductive attitudes and experiences of women who have previously undergone planned oocyte cryopreservation (OoC)?, Design: Retrospective questionnaire-based cohort study involving women who had previously undergone planned OoC between January 2009 and September 2016 at a single centre. Eligible women were contacted via e-mail and invited to complete an anonymous standardized questionnaire that had been developed to evaluate their current relationship status and reproductive situation, their attitudes towards planned OoC and their future reproductive intentions., Results: Of 460 women who had completed at least one OoC cycle, questionnaires were obtained from 138 women. After a mean (± SD) follow-up of 4.5 ± 2.4 years, two-thirds of respondents (65%) anticipated using their oocytes at some point in the future. The respondents reported an overwhelmingly positive attitude towards planned OoC, with 98% indicating they would recommend this intervention to others. Overall, 83% of respondents were single at the time they requested OoC but only 44% were single at the time they completed the survey. While 43/62 (69%) of women became pregnant after undergoing OoC, the majority 30/43 (70%) of these pregnancies were achieved without using their vitrified oocytes. Finally, 13/28 (46%) who used their cryopreserved oocytes stated that they had achieved a live birth., Conclusions: The majority of women who undergo OoC do not regret their experience and many have found a partner in subsequent years. Twenty-one per cent of respondents who attempted to conceive after OoC had a live birth using their cryopreserved oocytes., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does the levonorgestrel-releasing intrauterine device (LNG-IUD) influence cumulative live birth rate (CLBR) in oocyte donor cycles?, Design: Retrospective cohort study based on prospectively collected data from 1 May 2009 to 31 December 2017, without attrition, consisting of 491 consecutive cycles of vitrified oocyte donation, none lost to follow-up (unique donor-recipient pairs). All donors underwent ovarian stimulation using gonadotrophin releasing hormone (GnRH) antagonist co-treatment and GnRH agonist trigger. CLBR was chosen as primary outcome measure., Results: In total, 103 (21.0%) cycles were carried out in donors carrying a LNG-IUD. In 388 (79.0%) cycles, no LNG-IUD was present. After confounder-adjustment, the use of an LNG-IUD did not have a statistically significant influence on CLBR., Conclusions: The LNG-IUD does not negatively affect CLBR., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does the type of pituitary suppression protocol influence cumulative live birth rate (LBR) in Bologna poor responders treated with corifollitropin alfa (CFA)?, Design: Retrospective cohort analysis including poor responder patients fulfilling the Bologna criteria who underwent their first intracytoplasmic sperm injection cycle using a CFA-based ovarian stimulation protocol between 2011 and 2017. The starting dose of CFA was 150 µg. The primary outcome was cumulative LBR, defined as the first delivery of a live born resulting from the fresh and all the subsequent frozen embryo transfers., Results: A total of 717 cycles were divided into three groups: A (gonadotrophin-releasing hormone [GnRH] antagonist protocol, n = 407), B (long GnRH agonist protocol, n = 224) and C (short GnRH agonist protocol, n = 86). Cumulative LBR did not significantly differ between groups (20.1% versus 17.4% versus 14.0%; P = 0.35). Significantly more patients in Group A had supernumerary embryos cryopreserved (28.3% versus 18.4% versus 11.6%; P < 0.001). Days of additional highly purified human menopausal gonadotrophin 300 IU injections following CFA were significantly different between Groups A, B and C (3 versus 5 versus 3 days; P < 0.001). Multivariate logistic regression analysis showed that the number of oocytes retrieved remained an independent predictive factor (odds ratio 1.23, 95% confidence interval 1.16-1.31) for cumulative LBR., Conclusions: Poor responders according to the Bologna criteria in whom CFA is used for ovarian stimulation had comparable cumulative LBR, irrespective of the type of pituitary suppression. An increase in number of oocytes retrieved is an independent variable related to cumulative LBR., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Progesterone overproduction during ovarian stimulation is associated with lower live birth rates (LBR) after fresh embryo transfer. Therefore, circulating P concentrations on the day of HCG administration are frequently measured in clinical practice and followed by an elective cryopreservation strategy whenever late-follicular elevated P (LFEP) occurs. A recent study concluded that the duration of LFEP >1.00 ng/mL prior to HCG administration may also affect clinical pregnancy rates. The objective of this current study was to assess whether this hypothesis was reproducible using LBR as the primary outcome., Design: Retrospective analysis including women undergoing IVF/ICSI between 2010-2015. LBR were compared among different P elevation duration subgroups (0, 1 or >1 day) using two LFEP thresholds (>1.00 ng/mL and >1.50 ng/mL)., Results: The duration of LFEP >1.00 ng/mL was not associated with a significant decrease in LBR according to whether the patient had LFEP lasting for 0, 1 or >1 days (29.9%, 30.3% and 26.3%, respectively). Conversely, when using >1.50 ng/mL as the LFEP threshold, LBR decreased significantly (30.3% 20.4% and 20.5%, respectively). However, the relative frequency of having LFEP >1.50 ng/mL for >1 day was exceedingly rare (1.9%) and the additional benefit of evaluating LFEP beyond the day of HCG triggering no longer remained statistically significant after confounder-adjustment with multivariable regression analysis., Conclusion: These results suggest a lack of benefit in measuring serum P in the days preceding HCG administration, since LBR in women with LFEP >1 day do not vary significantly from those with LFEP detected only on the day of HCG administration., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The evaluation of endometrial thickness (EMT) is still part of standard cycle monitoring during IVF, despite the lack of robust evidence of any value of this measurement to predict little revalidation in contemporary medical practice; other tools, however, such as endocrine profile monitoring, have become increasingly popular. The aim of this study was to reassess whether EMT affects the outcome of a fresh embryo transfer in modern-day medicine, using a retrospective, single-centre cohort of 3350 IVF cycles (2827 women) carried out between 2010 and 2014. In the multivariate regression analysis, EMT was non-linearly associated with live birth, with live birth rates being the lowest with an EMT less than 7.0 mm (21.6%; P < 0.001) and then between 7.0 mm and 9.0 mm (30.2%; P = 0.008). An EMT less than 7.0 mm was also associated with a decrease in neonatal birthweight z-scores (-0.40; 95% CI -0.69 to -0.12). In conclusion, these results reaffirm the use of EMT as a potential prognostic tool for live birth rates and neonatal birthweight in contemporary IVF, namely when considered together with other ovarian stimulation monitoring methods, such as the late-follicular endocrine profile., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

As the oocyte is the starting point for a new life, artificial reproductive technology (ART) techniques should not affect the (ultra) structural and functional integrity, or the developmental competence. Oocyte vitrification -one of the most significant achievements in human ART during the past decade- should therefore be a safe and efficient technique. This review discusses the principles and developments of the existing and future techniques, applications possibilities and safety concerns. The broad range of vitrification media and devices that are currently available, show differences in their effects on the oocyte ultrastructure and preimplantation development. It is not yet fully decided whether this has an influence on the obstetric and neonatal outcome, since only limited information is available with different media and devices. For autologous oocytes, the obstetric and neonatal outcomes appear promising and comparable to pregnancies obtained with fresh oocytes. This however, is not the case for heterologous fresh or vitrified oocytes, where the immunological foreign foetus induces adverse obstetric and neonatal outcomes. Besides the oocyte vitrification process itself, the effect of multiple stimulations (for oocyte banking or for oocyte donors), seems to influence the possibility to develop gynaecological cancers further in life. Automated vitrification/warming should offer a consistent, cross-contamination free process that offers the highest safety level for the users. They should also produce more consistent results in survival, development and clinical pregnancies between different IVF clinics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Controversy exists about the risk of microbiological contamination from direct contact with unsterile liquid nitrogen during oocyte vitrification. The aim of this observational study was to evaluate the effectiveness of oocyte vitrification using a high-security closed vitrification system in a donation programme. Oocyte vitrification was performed using CBS High Security closed straws (Cryo Bio System) with DMSO/ethylene glycol/sucrose as the cryoprotectant (Irvine Scientific freeze kit). A total of 123 vitrified metaphase-II oocytes were warmed in 20 recipient cycles (6.2 warmed oocytes per recipient); of these, 111 oocytes (90.2%) survived vitrification and warming. All surviving oocytes were microinjected and 86 (77.5%) were normally fertilized, of which 53 (61.6%) developed up to good-quality day 3. Ten embryo transfers resulted in a clinical pregnancy (50.0%) and an ongoing clinical pregnancy rate of 45%. Five revitrified embryos were warmed in three warming cycles (survival rate 100%). These transfers resulted in an additional ongoing twin pregnancy, leading to a cumulative ongoing pregnancy rate per patient of 50% (10/20). The ongoing implantation rate per warmed oocyte and per injected oocyte was 10.6% (13/123) and 11.7% (13/111). The present data demonstrate that oocyte vitrification using a closed vitrification device yields excellent oocyte survival, fertilization and embryo development., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)