Continuous ovarian stimulation: a proof-of-concept study exploring the uninterrupted use of corifollitropin α in DuoStim cycles for enhanced efficiency and patient convenience (Alicante protocol).

Objective: To explore the use of weekly continuous dosing of corifollitropin α in DuoStim cycles. Design: Pilot-matched case-control study. Setting: Private fertility center. Patients: Cases were defined as DuoStim cycles performed from November 2022 to May 2023 receiving weekly continuous dosing of corifollitropin α (n = 15). Controls were chosen from a database comprising DuoStim cycles conducted at our institution during the years 2021/2022. Matching was done on a 1-to-1 basis, based on antimüllerian hormone values (±0.4 pmol/L) and age (n = 15). Interventions: Injections of corifollitropin α once every 8 days, along with uninterrupted oral administration of micronized progesterone 200 mg/d (for luteinizing hormone surge prevention) throughout the follicular and luteal phases for ovarian stimulation. Oocyte retrieval. Main outcome measures: Total number of cumulus-oocyte complexes and metaphase II oocytes obtained in follicular + luteal phase stimulation. Secondary outcomes evaluated fertilization rates, number of blastocysts, days of stimulation, number of injectables required, and gonadotropin cost. Results: The study group achieved similar total oocyte and MII yield vs. daily follicle-stimulating hormone protocol (13.3 ± 6.9 vs. 11.8 ± 6.1 and 10.4 ± 6.3 vs. 9.2 ± 4.6, respectively). All secondary outcomes showed no significant differences. The study group experienced a significant reduction of injections to complete a DuoStim cycle (4.5 ± 1.4 vs. 35.2 ± 12.2; mean deviation -30.7; 95% confidence interval, -37.5- to -23.9)]. Conclusions: Corifollitropin α on a weekly basis throughout a DuoStim cycle yields an equivalent number of oocytes as standard daily follicle-stimulating hormone administration while drastically reducing the number of required injections. Trial registration number: NCT05815719. EudraCT: 2022-003177-32.

The impact of (very) young donor age on euploid rates: An analysis of 1831 trophectoderm biopsies evaluated with 24-chromosome NGS screening in oocyte donation cycles.

RESEARCH QUESTION: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles? DESIGN: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables. RESULTS: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences. CONCLUSION: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups.

Impact of Group vs Individual Embryo Culture Strategies on Blastocyst and Clinical Outcomes.

Embryo culture is one of the most important steps in an assisted reproduction laboratory. Embryos can be cultured individually, one embryo per media drop, or in groups, culturing several embryos in the same media drop. Due to the controversy generated on this subject, we wondered which embryo culture method would have the best results in terms of quality and blastocyst formation rate. We designed a prospective randomized study comparing two different embryo culture strategies: group and individual embryo culture. The data were obtained from 830 embryos from 103 egg donation treatments. The zygotes were randomized into two groups: individual culture (group 1) or group culture (group 2). The embryos were cultured in 35-µl drops until day 5 when they were classified morphologically. We observed a significant increase in the blastocyst formation rate and in the usable embryo rate in individual culture on day 5 compared to group culture. However, good embryo quality (A/B blastocysts), implantation, and pregnancy rates were similar regardless of the type of embryo-culture. As a conclusion, individual culture may increase blastocyst formation rate and may benefit embryo quality on day 5. Our results support previous reports suggesting that individual culture could improve embryo development.

Endometrial receptivity in women with endometriosis.

As endometriosis is recognized as a contributing factor to infertility, prompting couples to embark on Assisted Reproductive Technology (ART) treatments, it becomes crucial to comprehend the extent and way this condition can affect success rates. Natural conception data reveal lower success rates for women with endometriosis, yet the same cannot be extrapolated to the outcomes of in vitro fertilization (IVF). In recent years, advancements in the ART process, particularly the distinct stages of the IVF pathway and investigations into embryo quality have shown a comparable rate of embryonic quality and chromosomal normalcy (euploidy) between embryos obtained from individuals with or without endometriosis. Thus, the primary question that lingers relates to the functionality of the endometrium. This review addresses whether endometriosis can influence endometrial receptivity and implantation rates.

Random-start ovarian stimulation in an oocyte donation programme: a large, single-centre, experience.

RESEARCH QUESTION: Do live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols? DESIGN: Retrospective analysis of 891 ovarian stimulations in egg donors (January-December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1-3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome. RESULTS: Duration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable. CONCLUSIONS: No notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles.

Progesterone levels on the day of embryo transfer using a single pessary of 400mg of vaginal progesterone vs. 200mg x2 pessaries in hormonal replacement cycles.

OBJECTIVE: Does the use of 400mg pessaries of micronized progesterone provide comparable results as pessaries of 200mg x2, in terms of progesterone levels in hormonal replacement cycles for embryo transfer?. METHODS: Retrospective cohort study based on 299 embryo transfer treatments under artificial endometrial preparation carried out at Instituto Bernabeu. 131 patients received 1 pessary of 400 mg b.i.d. (group A) and 168 received 2 pessaries of 200 mg b.i.d. (group B). RESULTS: Mean serum progesterone levels were similar between groups (A: 13.64±4.47ng/mL vs. B: 13.88±7.17ng/mL). There were no differences in suboptimal progesterone levels between groups (A: 11.5% vs. B: 16.8%). In terms of patients receiving additional progesterone supplementation, there were no differences between groups (A: 26% vs. B: 35.3%.). No differences between groups were observed in clinical outcomes: pregnancy rate (PR) (A: 55% vs. B: 54.8%), biochemical pregnancy loss rate (BPLR) (A: 13.4% vs. B: 17.6%), miscarriage rate (MR) (A: 17.9% vs. B: 19.8%) and ongoing pregnancy rate (OPR) (A: 36.5% vs. B: 34.1%). CONCLUSIONS: One progesterone pessary of 400mg (Cyclogest®) twice daily appears to be non-inferior to the use of two-200mg pessaries twice daily in terms of progesterone levels in HRT cycles.

Influence of the starting day of luteal phase stimulation on double stimulation cycles.

Background: Double ovarian stimulation is one of the most used strategies in poor-prognosis patients. There is a high heterogeneity between the studies regarding the execution of this stimulation protocol. The aim of this study was to investigate whether the day on which luteal phase stimulation begins after the first oocyte retrieval affects ovarian response in DuoStim cycles. Methods: This observational and retrospective study included 541 DuoStim cycles between January 2018 and December 2021 in a private fertility clinic. Patients were assigned to 4 groups according to the timing of the onset of luteal phase stimulation after oocyte retrieval (0-2nd day, 3rd day, 4th day and 5th-6th day). The primary outcome was the number of oocytes retrieved in the luteal phase in each group. Results: No differences were found between groups in the number of oocytes collected (5.12 ± 3.56 vs. 5.39 ± 3.74 vs. 5.61 ± 3.94 vs. 5.89 ± 3.92; p=0,6), MII or number of follicles. An increase in the duration of stimulation was found when stimulation started on the 4th day (10.42 ± 2.31 vs. 10.68 ± 2.37 vs. 11.27 ± 2.40 vs. 10.65 ± 2.37 days, p=0,033). A lower number of fertilized oocytes was observed when stimulation began before the fourth day (3.36 ± 2.80 vs. 3.95 ± 2.53 vs. 4.03 ± 2.73 vs. 4.48 ± 3.11; p=0,036). The number of blastocysts was higher when the stimulation started 5-6 days after retrieval (1.82 ± 1.74 vs. 2.13 ± 1.61 vs. 2.33 ± 2.06 vs. 2.91 ± 2.39; p= 0,030). Discussion: The number of oocytes retrieved does not differ depending on the day that stimulation begins. However, oocytes competence in terms of fertilized oocytes and blastulation, appears to be lower when the second stimulation starts before the fourth day after oocyte retrieval.

Noninvasive preimplantation genetic testing using the embryo spent culture medium: an update.

PURPOSE OF REVIEW: The presence of cell-free DNA (cf-DNA) in the embryo spent culture medium allows to develop a noninvasive PGT-A (niPGTA). Noninvasive PGT-A may provide a simpler, safer and less costly approach to preimplantation genetic testing of aneuploidy (PGT-A). Furthermore, niPGTA would provide wider access to embryo genetic analysis and circumvent many legal and ethical considerations. However, the concordance rate between the results obtained by PGT-A and niPGTA varies among studies and, their clinical utility has not been already demonstrated. This review evaluates the niPGTA reliability based on SCM and adds new knowledge about the clinical relevance of SCM for noninvasive PGT-A. RECENT FINDINGS: The most recent concordance studies evaluating the accuracy of niPGTA using SCM showed a high variation in the informativity rate of SCM and the diagnostic concordance. Also, sensitivity and specificity showed similar heterogeneous results. Therefore, these results do not support the clinical utility of niPGTA. Regarding clinical outcome, the data are initial and further research, including randomized and nonselection studies are needed. SUMMARY: Further research, including randomized and nonselection studies, as well as optimization of embryo culture conditions and medium retrieval, are needed to improve the reliability and clinical utility of niPGTA.

Characterization of the Endometrial Microbiome in Patients with Recurrent Implantation Failure.

An abnormal endometrial microbiota has been associated with implantation failure; therefore, it may be important to evaluate it in order to improve reproductive outcomes in infertile patients. The main objective of our study was to compare the endometrial microbiome of patients with recurrent implantation failure (RIF) and control patients undergoing assisted reproduction treatment (ART). A prospective cohort study including forty-five patients with their own or donated gametes. The endometrial microbiome was analysed by massive sequencing of the bacterial 16S rRNA gene. Different bacterial communities were detected in RIF and control patients. Lactobacillus stands out as the most frequent genus, with 92.27% in RIF patients and 97.96% in control patients, and significant differences were reported between the two groups (p = 0.002). No significant differences were found regarding alpha diversity index. In beta diversity analysis, a significant trend was observed in the separation of the bacterial community between established groups (p < 0.07). Relative abundance analysis identified genera Prevotella (p < 0.001), Streptococcus (p < 0.001), Bifidobacterium (p = 0.002), Lactobacillus (p = 0.002) and Dialister (p = 0.003). Our results demonstrated the existence of an endometrial microbiota characteristic of RIF patients and showed that there might be a relationship between population of the endometrial microbiome and embryo implantation failure, providing us the possibility to improve clinical results in this patients.

Exploring self-detection of the endogenous LH surge using a urine test as a tool to predict a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles.

OBJECTIVE: Is self-detection of the endogenous LH surge using a urine testing a reliable method to confirm a successful gonadotropin-releasing hormone agonist (GnRHa) trigger in IVF cycles? METHODS: Prospective observational study including a total of 103 oocyte donation cycles between November 2019 and January 2020. Urine LH testing (Akralab SL, Spain, cut-of value 30 mIU/mL) was performed at home in samples from the first micturition in the morning after the GnRHa trigger and a picture of the result was sent to the nurse coordinator; this information was concealed and only disclosed after oocyte aspiration. RESULTS: From the total group, two cycles were excluded. A total of 101 oocyte donors performed the LH urine testing, all proceeded to oocyte aspiration and were included in final analysis. A total of 85 (84.2%) had a positive LH test and an uneventful oocyte retrieval with good retrieval rates (false positive rate: 0%). A total of 16 had a negative LH test (15.8%) and had a good oocyte retrieval rates (false negative rate: 15.8%). There were no cases of empty follicle syndrome. CONCLUSIONS: Due to a high false negative rate, self-testing of endogenous LH release using a LH urine test when performed approximately 12-hours after triggering does not seem to be a reliable method to predict a suboptimal response to gonadotropin-releasing hormone.

Does mRNA COVID-19 vaccination in oocyte donors impact ovarian stimulation parameters or IVF outcomes for recipients?

RESEARCH QUESTION: What is the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in young oocyte donors in terms of ovarian response to stimulation, fertilization rate, embryo development and clinical outcomes in recipients? DESIGN: This retrospective, multicentre cohort study evaluated 115 oocyte donors who had undergone at least two ovarian stimulation protocols (before and after complete SARS-CoV-2 vaccination) between November 2021 and February 2022. Comparisons were made of the primary outcomes of days of stimulation, total dose of gonadotrophins and laboratory performance in ovarian stimulation in oocyte donors before and after vaccination. A total of 136 cycles in matched recipients were analysed as secondary outcomes and, from those, 110 women received a fresh single-embryo transfer, with analysis of biochemical ß-human chorionic gonadotrophin concentrations and rates of clinical pregnancy with heartbeat. RESULTS: Longer stimulation was required in the post-vaccination than pre-vaccination group (10.31 ± 1.5 versus 9.51 ± 1.5 days; P < 0.001) along with higher gonadotrophin consumption (2453.5 ± 740 versus 2235.5 ± 615 IU; P < 0.001) with a similar starting dose of gonadotrophins in both groups. More oocytes were retrieved in the post-vaccination group (16.62 ± 7.1 versus 15.38 ± 7.0; P = 0.02). However, the number of metaphase II (MII) oocytes was similar between groups (pre-vaccination 12.61 ± 5.9 versus post-vaccination 13.01 ± 6.6; P = 0.39) and the ratio of MII/retrieved oocytes favoured the pre-vaccination group (0.83 ± 0.1 versus 0.77 ± 0.2 post-vaccination; P = 0.019). In recipients with a similar number of provided oocytes, the fertilization rate, total number of obtained blastocysts, number of top-quality blastocysts, and rates of biochemical pregnancy and clinical pregnancy with heartbeat were not significantly different between groups. CONCLUSIONS: This study shows no adverse influence of mRNA SARS-CoV-2 vaccination on ovarian response in a young population.

Conventional follicular-phase ovarian stimulation vs. luteal-phase stimulation in suboptimal responders: a randomized controlled trial.

Objective: To compare the oocyte yield between follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in suboptimal responders. Design: Prospective, randomized, crossover clinical trial. Patients: Forty-one patients with infertility according to the POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria (1b/2b). Interventions: Crossover study on 2 assigned ovarian stimulations that started randomly in the follicular or luteal phase. The in vitro fertilization cycles were not consecutive but separated in time (45 days to 6 months). The random crossover design ensured that all subjects received the first treatment by chance. Main Outcome Measures: The primary objective was the number of cumulus-oocyte complexes retrieved in each cycle. Secondary objectives were number of metaphase II and fertilized oocytes, additional doses of recombinant follicle-stimulating hormone, and the duration of ovarian stimulation (days). Results: The mean number of cumulus-oocyte complexes retrieved was similar between the FPS and LPS groups (7.5 ± 4.6 vs. 7.0 ± 4.1; 95% confidence interval [CI] for the mean, 5.8-8.7 vs. 5.6-8.3, respectively; the difference between means, -0.5; 95% CI, -1.8 to +1.5). Similarly, the mean number of metaphase II oocytes retrieved was not different between the FPS and LPS groups (5.4 ± 3.6 vs. 5.2 ± 2.8; 95% CI for the mean, 4.2-6.5 vs. 4.3-6.1, respectively; the difference between means, -0.2; 95% CI, -1.2 to +1.1). Moreover, the secondary objectives were similar between FPS and LPS groups. Conclusions: In this study, the oocyte yield in LPS did not increase in suboptimal responders compared with that in FPS when the onset of LPS was separated in time from FPS. Clinical Trial Registration Number: NCT039393990 https://beta.clinicaltrials.gov/study/NCT03939390.

Application of machine learning to predict aneuploidy and mosaicism in embryos from in vitro fertilization cycles.

BACKGROUND: The factors associated with embryo aneuploidy have been extensively studied. Mostly maternal age and to a lesser extent male factor and ovarian stimulation have been related to the occurrence of chromosomal alterations in the embryo. On the other hand, the main factors that may increase the incidence of embryo mosaicism have not yet been established. OBJECTIVE: This study aimed to establish a machine learning model that would allow prediction of aneuploidies and mosaicism in embryos conceived via in vitro fertilization, and thus help to determine which variables are associated with these chromosomal alterations. STUDY DESIGN: The study design was observational and retrospective. A total of 6989 embryos from 2476 cycles of preimplantation genetic testing for aneuploidies were included (January 2013 to December 2020). The trophoectoderm biopsies on day-5, -6, or -7 blastocysts were analyzed by preimplantation genetic testing for aneuploidies (PGT-A). The different maternal, paternal, couple, embryo, and in vitro fertilization cycle characteristics were recorded in a database (22 predictor variables) from which predictive models of embryo aneuploidy and mosaicism were developed; 16 different unsupervised classification machine learning algorithms were used to establish the predictive models. RESULTS: Two different predictive models were performed: one for aneuploidy and the other for mosaicism. The predictor variable was of multiclass type because it included the segmental- and whole-chromosome alteration categories. The best predicting models for both aneuploidies and mosaicism were those obtained from the Random Forest algorithm. The area under ROC curve (AUC) value was 0.792 for the aneuploidy explanatory model and 0.776 for mosaicism. The most important variable in the final aneuploidy model was maternal age, followed by paternal and maternal karyotype and embryo quality. In the predictive model of mosaicism, the most important variable was the technique used in preimplantation genetic testing for aneuploidies and embryo quality, followed by maternal age and day of biopsy. CONCLUSION: It is possible to predict embryo aneuploidy and mosaicism from certain characteristics of the patients and their embryos.

FSH receptor genotype and its influence on the results of donor ovarian stimulation using corifollitropin alfa.

RESEARCH QUESTION: Does the FSH receptor (FSHR) genotype influence the results of donor ovarian stimulation using corifollitropin alfa? DESIGN: A prospective cohort study was performed including 152 oocyte donor ovarian stimulations: group 1 (n = 80) using a single dose of 150 µg of corifollitropin alpha; and group 2 (n = 72) using in addition to corifollitropin alpha, continued stimulation using recombinant FSH 225 IU daily. Allelic discrimination was used to genotype the FSHR p.N680S polymorphism. Linear regression analysis was performed to study the differences between groups. RESULTS: No differences in clinical characteristics between genotypes were reported. Overall, the results of ovarian stimulation were better in oocyte donors with SN and NN genotypes compared with SS in terms of the number of retrieved oocytes (15.78 versus 10.83; P = 0.008) and retrieved metaphase II (MII) oocytes (12.34 versus 9.00; P = 0.032). Corresponding differences were also observed in group 1 for the number of retrieved oocytes (13.83 versus 7.50, P = 0.018) and retrieved MII oocytes (10.24 versus 5.42; P = 0.038). However, in group 2 no significant differences were found for oocytes retrieved (17.55 versus 13.06, P = 0.064) or MII oocytes (14.25 versus 11.39; P = 0.12). CONCLUSIONS: This study suggests that ovarian stimulation protocols with corifollitropin alfa in women with the SS genotypes could be associated with fewer oocytes and MII oocytes retrieved. Despite the fact that corifollitropin alfa has a longer half-life, the results for the SS genotype do not match those for the other genotypes, so other factors must be involved. Therefore, to tailor treatments, it would be advisable to genotype women at p.N680S of the FSHR.

Cervical pessary and cerclage placement for preterm birth prevention and cervicovaginal microbiome changes.

INTRODUCTION: Our objective was to compare the vaginal microbiome in low-risk and high-risk pregnant women and to explore a potential association between vaginal microbiome and preterm birth. MATERIAL AND METHODS: A pilot, consecutive, longitudinal, multicenter study was conducted in pregnant women at 18-22 weeks of gestation. Participants were assigned to one of three groups: control (normal cervix), pessary (cervical length ≤25 mm) and cerclage (cervical length ≤25 mm or history of preterm birth). Analysis and comparison of vaginal microbiota as a primary outcome was performed at inclusion and at 30 weeks of gestation, along with a follow-up of pregnancy and perinatal outcomes. We assessed the vaginal microbiome of pregnant women presenting a short cervix with that of pregnant women having a normal cervix, and compared the vaginal microbiome of women with a short cervix before and after placement of a cervical pessary or a cervical cerclage. RESULTS: The microbiome of our control cohort was dominated by Lactobacillus crispatus and inners. Five community state types were identified and microbiome diversity did not change significantly over 10 weeks in controls. On the other hand, a short cervix was associated with a lower microbial load and higher microbial richness, and was not correlated with Lactobacillus relative abundance. After intervention, the cerclage group (n = 19) had a significant increase in microbial richness and a shift towards community state types driven by various bacterial species, including Lactobacillus mulieris, unidentified Bifidobacterium or Enterococcus. These changes were not significantly observed in the pessary (n = 26) and control (n = 35) groups. The cerclage group had more threatened preterm labor episodes and poorer outcomes than the control and pessary groups. CONCLUSIONS: These findings indicate that a short cervix is associated with an altered vaginal microbiome community structure. The use of a cerclage for preterm birth prevention, as compared with a pessary, was associated with a microbial community harboring a relatively low abundance of Lactobacillus, with more threatened preterm labor episodes, and with poorer clinical outcomes.

Vitrification does not affect birth weight: lessons from the oocyte donation model.

RESEARCH QUESTION: Is embryo cryopreservation a cause of high birth weight and large for gestational age (LGA) in singletons resulting from vitrified-warmed embryo transfer? DESIGN: Retrospective cohort study evaluating 670 oocyte recipients who underwent fresh (367 cycles) or vitrified-warmed embryo transfer (303 cycles) at Instituto Bernabeu between July 2017 and March 2019. All single blastocyst transfers carried out in an artificial cycle that resulted in a singleton live birth were included. RESULTS: Maternal age (42.21 ± 4.45; 42.79 ± 3.83; P = 0.519), body mass index (23.34 ± 3.69; 23.80 ± 3.78; P = 0.075), gestational age (38.96 ± 1.97; 38.77 ± 2.15; P = 0.207), maternal smoking (10.8%; 13.0%; P = 0.475), gestational diabetes (4.9%; 4.3% P = 0.854), preeclampsia (2.7%; 5.6%; P = 0.074), hypertensive disorders (3.3%; 2.3%; P = 0.494), maternal parity (multiparous 18.5%; 14.5%; P = 0.177) and liveborn gender (female 44.5%; 48.8%; P = 0.276) were not significantly different between fresh or vitrified-warmed groups. Endometrial thickness was significantly higher in the fresh versus vitrified-warmed group (8.83 ± 1.73 versus 8.57 ± 1.59; P = 0.035, respectively). Oocyte donor height was similar between the fresh versus vitrified-warmed group (163.22 ± 5.88 versus 164.27 ± 6.66 cm; P = 0.057, respectively). Mean birth weight was not significantly different (3239.21 ± 550.43; 3224.56 ± 570.83; adjusted P = 0.058). No differences were observed in macrosomia (7.1%; 6.3%; adjusted OR 0.857, 95% CI 0.314 to 2.340, P = 0.764), LGA (6.0%; 6.7%; adjusted OR 0.450, 95% CI 0.176 to 1.149, P = 0.095), pre-term birth (10.9%; 9.0% adjusted P = 0.997), very pre-term birth (0.8%; 1.3%; adjusted P = 1.000), extremely pre-term birth (0%; 1.0%; adjusted P = 0.998); underweight (10.0%; 7.0%; adjusted P = 0.050); very low weight (0.6; 1.1%; adjusted P = 1.000) and small for gestational age (1.9%; 0.7%; adjusted P = 0.974) between fresh or vitrified-warmed groups. CONCLUSION: This study eliminates potential confounders that might influence fetal growth and demonstrates that embryo vitrification and warming procedures do not affect birth weight.

Comparison of the assisted reproductive technology outcomes between conventional IVF and ICSI with donor oocytes in normozoospermic patients.

There is no evidence for the superiority of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) using donor oocytes. This retrospective descriptive study aimed to compare the outcomes of conventional IVF (n = 506) and ICSI (n = 613) with donor oocytes in (n = 968) normozoospermic patients. Although the fertilization rate was statistically higher in the ICSI group (p < 0.001), conventional IVF provided better results than ICSI with respect to embryo quality (number of grade A embryos, p < 0.001). In addition, we observed more blastocysts in the conventional IVF group (p < 0.001) and more good quality embryos were obtained for cryopreservation compared to ICSI (p < 0.001). Regarding clinical results, there were no statistical significant differences in the positive pregnancy test, clinical pregnancy and clinical miscarriage rates between IVF and ICSI. However, the implantation rate was statistically higher when IVF was performed (50.4% vs. 43.0%, p = 0.031, OR (95% CI): 1.185 (1.050-2.530)). In conclusion, with the use of normozoospermic samples in our oocyte donation programme, IVF offers more embryo efficiency and increased implantation rates than ICSI.

The Effect of Twisted Uterus Caused by Endometriosis or Myomatosis on Reproductive Treatment Outcomes.

Objective: Twisted uterus is detected when the body of the uterus is rotated from the cervical canal. This anomaly may be due to different causes, such as uterine fibroids, endometriosis or the presence of both. The study has aimed to compare the effect of the twisted uterus cause in terms of reproductive treatment outcomes. Materials and methods: It consisted of a retrospective study of twisted uterus cases with repeated implantation failure (more than three embryo transfers or four blastocysts transferred unsuccessfully) in our ultrasound department. The twisted uterus was defined when the vaginal probe needed to be rotated to assess the endometrial line thoroughly or when the coronal view was seen by 2D scan. From 2017 to 2020, 879 gynecological ultrasounds were performed. For statistical analysis, we carried out a logistical regression analysis adjusted by confounding factors. Results: From 145 patients included only 92 patients underwent reproductive treatments. With the known cause of uterine torsion. 56 patients with endometriosis, 18 with uterine myoma and the remaining 18 suffered from both. After assisted reproductive treatment, the endometriosis group showed the highest clinical pregnancy rate (53.57%) compared to myoma (22.22%) and endometriosis and myoma (38.89%) groups. Conclusion: Uterine myoma capable of causing uterine torsion may affect embryo implantation more than endometriosis. Prospective randomized studies with a larger number of patients would be needed to confirm these findings.

Impact of the Vaginal and Endometrial Microbiome Pattern on Assisted Reproduction Outcomes.

Uterine microbiota may be involved in reproductive health and disease. This study aims to describe and compare the vaginal and endometrial microbiome patterns between women who became pregnant and women who did not after in vitro fertilization. We also compared the vaginal and endometrial microbiome patterns between women with and without a history of repeated implantation failures (RIF). This pilot prospective cohort study included 48 women presenting to the fertility clinic for IVF from May 2017 to May 2019. Women who achieved clinical pregnancy presented a greater relative abundance of Lactobacillus spp. in their vaginal samples than those who did not (97.69% versus 94.63%; p = 0.027. The alpha and beta diversity of vaginal and endometrial samples were not statistically different between pregnant and non-pregnant women. The Faith alpha diversity index in vaginal samples was lower in women with RIF than those without RIF (p = 0.027). The alpha diversity of the endometrial microbiome was significantly higher in women without RIF (p = 0.021). There were no significant differences in the vaginal and endometrial microbiomes between pregnant and non-pregnant women. The relative abundance of the genera in women with RIF was different from those without RIF. Statistically significant differences in the endometrial microbiome were found between women with and without RIF.