Association between oocyte donors' or recipients' body mass index and clinical outcomes after first single blastocyst transfers-the uterus is the most affected.

OBJECTIVE: To assess whether high body mass index (BMI) in either oocyte donors or recipients is associated with poorer outcomes after the first single blastocyst transfer. DESIGN: Retrospective study including 1,394 first blastocyst single embryo transfers (SETs) conducted by 1,394 recipients during oocyte donation cycles with the gametes retrieved from 1,394 women (January 2019-July 2021). Four BMI clusters were defined for both donors and recipients (underweight: <18.5 kg; normal weight: 18.5-24.9 kg; overweight: 25-29.9 kg; and obese: ≥30 kg). SETTING: Network of private IVF centers. PATIENTS: A total of 1,394 recipients aged 42.4 ± 4.0 and with a BMI of 23.2 ± 3.8 kg/m2, and 1,394 donors aged 26.1 ± 4.2 and with a BMI of 21.9 ± 2.5 kg/m2. INTERVENTION: All oocytes were vitrified at 2 egg banks and warmed at 8 in vitro fertilization clinics that were part of the same network. Intracytoplasmic sperm injection, blastocyst culture, and either fresh or vitrified-warmed SETs were conducted. Putative confounders were investigated, and the data were adjusted through regression analyses. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate (LBR) per SET according to donors' and/or recipients' BMI. The main secondary outcome was the miscarriage rate (<22 gestational weeks) per clinical pregnancy. RESULTS: The LBR per blastocyst SET showed no significant association with donors' BMI. Regarding recipients' BMI, instead, the multivariate odds ratio was significant in obese vs. normal-weight recipients (0.58, 95% confidence interval, 0.37-0.91). The miscarriage rate per clinical pregnancy was also significantly associated with recipients' obesity, with a multivariate odds ratio of 2.31 (95% confidence interval, 1.18-4.51) vs. normal-weight patients. A generalized additive model method was used to represent the relationship between predicted LBR or miscarriage rates and donors' or recipients' BMI; it pictured a scenario where the former outcome moderately but continuously decreases with increasing recipients' BMI to then sharply decline in the BMI range of 25-35 kg/m2. The miscarriage rate, instead, increases almost linearly with respect to both donors' and recipients' increasing BMI. CONCLUSION: Obesity mostly affects the uterus, especially because of higher miscarriage rates. Yet, poorer outcomes can be appreciated already with a BMI of 25 kg/m2 in both oocyte donors and recipients. Finer markers of nutritional homeostasis are therefore desirable; recipients should be counseled about poorer expected outcomes in cases of overweight and obesity; and oocyte banks should avoid assigning oocytes from overweight donors to overweight and obese recipients.

Conventional ovarian stimulation vs. delayed single dose corifollitropin alfa ovarian stimulation in oocyte donors: a prospective randomized study. Tail trial.

The present study compares two protocols for ovarian controlled stimulation in terms of number of cumulus-oocyte complexes and metaphase II oocytes. We employed a single injection of 150mcg of corifollitropin alfa after a 7-day oral contraceptive pill-free interval for TAIL group and a conventional administration of corifollitropin alfa after a 5-day OCP-free interval with additional rFSH from 8th of ovarian controlled stimulation. Prospective, randomized, comparative, non-inferiority, opened and controlled trial carried out in 180 oocyte donors 31 were excluded, 81 were randomized to the control group and 68 to the TAIL group. No differences were found in the number of follicles larger than 14 and 17 mm at triggering day. However, a lower number of cumulus-oocyte complexes and metaphase II oocytes were obtained in TAIL group compared to the control group, expressed as median (interquartile range): 10.5 (5.5-19) vs. 14 [11-21] and 9 (4-13) vs. 12 (9-17) respectively. Additionally, the incidence of failed retrieval or metaphase II oocytes = 0 was higher in TAIL group 7(10.3%) vs. 1(1.2%) p = 0.024. The use of a single injection of corifollitropin alfa after a 7-day oral contraceptive pill-free interval in oocyte donors resulted in a lower number of cumulus-oocyte complexes and metaphase II oocytes. No additional rFSH was administered in this group. Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-001343-44/results.

Endometrial receptivity tests in reproduction: a SWOT analysis.

Endometrial receptivity and its management in assisted reproduction is now a significant focus of research interest. Endometrial receptivity tests, which analyze different panels of gene expression, are usually offered in fertility clinics to determine the women's individual 'window of implantation', providing a personalized timing for embryo transfer. However, there are still no definite indications on whether its inclusion in the study of the infertile couple or the study of patients with repeated implantation failure is essential.

The role of thrombophilias in reproduction: A swot analysis.

Thrombophilia is a group of inherited or acquired coagulation disorders that have been associated with reproductive failure. However, there are still no clear recommendations on whether its inclusion in the initial study of the infertile couple or patients with recurrent implantation failure is necessary. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of the repercussions of thrombophilia screening and treatment in reproduction are evaluated. To avoid possible subjectivity in the analysis and results of this study, researchers followed Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed bibliography seem to indicate that, pending new evidence, it would be advisable not to include thrombophilia screening in the initial baseline study of the infertile couple. There is no evidence to support a clear association between thrombophilia and implantation failure or infertility. Thrombophilia testing in this setting may increase cost, with minimal potential benefit and lead to inappropriate use of anticoagulants with possible deleterious adverse effects. Future well-designed studies are needed to assess the possible benefit of anticoagulant therapy in infertile thrombophilic patients with implantation failure.

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.

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.

Can probiotics enhance fertility outcome? Capacity of probiotics as a single intervention to improve the feminine genital tract microbiota in non-symptomatic reproductive-aged women.

Modifications in vaginal and endometrial microbiome and microbiota have been associated with fewer implantation rates and poorest pregnancy outcomes. Therefore, its study has emerged as a new biomarker in reproductive medicine. Despite the numerous papers published on probiotic use for vaginal dysbiosis and their actual wide empiric use especially for infertile patients, there is still no clear answer to justify their recommendation. The impact of probiotics on the vaginal or endometrial microbiota has often been investigated under a symptomatic altered vaginal microbial ecosystem, such as bacterial vaginosis. However 50% of women with bacterial vaginosis are asymptomatic. Actual clinical practice guidelines clearly recommend the use of specific antimicrobial agents for the management of symptomatic vaginal infections. Assuming this should be the management as well for an infertile population, what should be the treatment for the 50% non-symptomatic women presenting unfavorable vaginal/endometrial microbiota? The aim of this review is to assess the capacity of probiotics as a single intervention to alter the feminine genital tract microbiota in non-symptomatic reproductive-aged women.

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.

Sperm DNA fragmentation on the day of fertilisation is not associated with assisted reproductive technique outcome independently of gamete quality.

The evaluation of sperm DNA fragmentation has been postulated as a predictive molecular parameter of the semen fertilising potential, as well as the ability to give rise to a healthy embryo and an ongoing pregnancy. However, there are controversial results due to oocyte quality, the use of different measurement techniques and interpretation criteria. Our objective is to investigate if sperm DNA fragmentation on the day of fertilisation influences in vitro fertilisation (IVF) outcome in a prospective double-blind study. Three groups of patients were defined: (i) 68 couples undergoing intracytoplasmic sperm injection (ICSI) due to severe male factor with normal ovarian response (NOR); (ii) 113 couples undergoing conventional in vitro fertilisation (IVF) in our oocyte donation programme due to ovarian failure; and (iii) 150 low ovarian response (LOR) patients undergoing ICSI or IVF. TUNEL assay was performed from an aliquot of each capacitated semen sample to detect DNA fragmentation. There was no relationship between blood serum ß-hCG positive test, clinical pregnancy and first trimester miscarriage with DFI levels in NOR (p = 0.41, p = 0.36, p = 0.40), recipient (p = 0.49, p = 0.99 and p = 0.38) and LOR (p = 0.52, p = 0.20, p = 0.64) groups of patients, respectively. Therefore, ART outcomes are not affected by sperm DNA fragmentation independently of gamete quality.

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.

Methylenetetrahydrofolate reductase gene polymorphisms are not associated with embryo chromosomal abnormalities and IVF outcomes.

The aim of our study was to investigate the effect of maternal and embryo MTHFR C677T and A1298C polymorphisms on embryo aneuploidies and mosaicism and the correlation between these genetic variants in transferred euploid embryos and IVF outcomes. MTHFR genotype was analyzed in 77 women who performed an IVF/ICSI cycle with PGT-A. Moreover, to evaluate the effect of embryo MTHFR polymorphisms on embryo aneuploidies and mosaicism, the MTHFR genotype was analyzed in 191 biopsied embryos from the PGT-A cycles of these patients. Additionally, 218 DNA samples from trophectoderm biopsies belonging to a different group of patients were also genotyped. MTHFR polymorphisms were analyzed in a total amount of 409 trophectoderm samples. The main parameters analyzed were embryo aneuploidy and mosaicism rates. Finally, the IVF outcomes of 241 single euploid embryo transfers were assessed and compared between different MTHFR embryo genotypes. The aneuploidy rates were similar in embryos from homozygous normal women and women with at least one mutated allele (54.7% vs. 30.2% in 677C>T and 37.8% vs. 42.7% in 1298A>C). Furthermore, no differences were observed in the mosaicism rate (24.0% vs. 13.8% in 677C>T and 17.1% vs. 17.3% in 1298A>C). A similar analysis was performed, taking into account the embryo genotype results. No differences in aneuploidy rate were observed between the study groups. The only significant difference was the mosaicism rate among 677C>T genotype (13.5% in 677CC group vs. 5.4% in 677CT/TT; p = 0.019). Implantation rate, biochemical and clinical miscarriage rates, and ongoing pregnancy rate were compared between different embryo genotypes, and no statistically significant differences were found. In conclusion, the maternal MTHFR genotype did not influence embryo chromosomal abnormalities. Moreover, the embryo MTHFR genotype was not associated with embryo aneuploidy or IVF outcomes such as implantation, pregnancy loss, and ongoing pregnancy when euploid embryos were transferred.Abbreviations: MTHFR: methylenetetrahydrofolate reductase; IVF: in vitro fertilization; PGT-A: preimplantation genetic testing for aneuploidies; SAM: S-adenosyl methionine; SNP: single nucleotide polymorphism; SPSS: Statistical Package for Social Sciences; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; hCG: human chorionic gonadotropin; PBS: phosphate buffered saline; CGH: comparative genomic hybridization; NGS: next generation sequencing.

Impact of chronic endometritis in infertility: a SWOT analysis.

Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chronic endometritis in the initial baseline study before assisted reproduction in order not to delay other assisted reproduction treatments. However, it would be advisable in cases of repetitive implantation failure and pregnancy loss after having undergone IVF with viable embryos and before continuing with costly reproductive processes, since results could be improved. The development of randomized studies assessing the impact of antibiotic treatment as a possible therapeutic option in infertile women with chronic endometritis, as well as the possible impact on endometrial microbiota and receptivity/implantation, would allow for the establishment of more precise clinical guidelines in this regard.

4D ultrasound as a method to assess uterine peristalsis.

OBJECTIVE: To study uterine peristalsis using step-by-step 4-dimensional (4D) ultrasound assessment video, explore its relationship with progesterone levels in a select in vitro fertilization population, and assess the reproducibility of the technique. DESIGN: Four-dimensional uterine ultrasound and a retrospective analysis of outcomes in relation with progesterone levels. The videos were also analyzed by a senior doctor, junior doctor, and a nurse for their reproducibility. SETTING: Instituto Bernabeu of Alicante is a private clinic. PATIENT(S): The study included 197 consecutive patients undergoing in vitro fertilization (from 2018 to 2019) with a history of recurrent implantation failure (defined as unsuccessful implantation of a total number of ≥3 blastocysts originated from oocyte donation cycles). Because it is known that most failures are attributed to the quality of the embryo, we deemed it important to explore the potential uterine factors explaining the failures in oocyte donation cycles, the use of which decreases the probability of embryo-related factors influencing it. INTERVENTION(S): The participants were evaluated for uterine contractions and serum progesterone levels (10-30 minutes before the embryo transfer procedure). Uterine contractility (UC) was assessed by recording a 6-minute-long video using a 4D mode (Voluson E10; General Electric, Boston, MA), which was performed by a single operator (B.M.). MAIN OUTCOMES MEASURE(S): The contractions were seen like waves going through the endometrial cavity. They were counted on a ×15 accelerated recording video. To define high-frequency UC, we separated uterine peristalsis (contractions per minute [cpm]) into quartiles. The highest quartile defined the hypercontractility group (>1.51 cpm; n = 41), considering the remaining quartiles as the normal contractility group (≤1.51 cpm; n = 156). The Mann-Whitney U test was performed. The intraclass correlation coefficient was used to validate variability. P <.05 was considered significant. SPSS version 21.0 was used for the statistical analysis. The institutional review board's approval was obtained. RESULT(S): Overall, an average of 1.1 cpm was found in the study population. There were no differences between the groups (hypercontractility vs. normal contractility) in terms of patient age and the presence of any uterine factor (adenomyosis, myomas, adhesions, or polyps). An inverse association was observed between UC and progesterone levels. Low progesterone levels (15.9 vs. 19.5 ng/mL; P = .027) were observed in the HUP and NUP group, respectively. The intraclass correlation coefficient to evaluate the interobserver variability was 0.75 (0.63-0.85; P = .000). CONCLUSION(S): Four-dimensional ultrasound assessment provides a dynamic view of uterine contractions, including their directionality and frequency. Even though recurrent implantation failure is yet a title of obscure definition and probably associated with multiple factors, a subgroup of patients with elevated UC associated with "low" progesterone levels may have a potential effect on their outcomes. Four-dimensional scan evaluation of UC constitutes a promising diagnostic tool in clinical practice; however, larger studies confirming our initial results are still pending.

Consistent results of non-invasive PGT-A of human embryos using two different techniques for chromosomal analysis.

RESEARCH QUESTION: Are discordances in non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) results attributable to the technique used for chromosomal analysis? DESIGN: A prospective blinded study was performed (September 2018 to December 2019). In total 302 chromosomal analyses were performed: 92 trophectoderm PGT-A biopsies and their corresponding spent embryo culture medium (SCM) evaluated by two methods (n = 184), negative controls (n = 8), and trophectoderm and inner cell mass biopsies from trophectoderm-aneuploid embryos (n = 18). Trophectoderm analyses were carried out using Veriseq (Illumina), and SCM was analysed using Veriseq and NICS (Yikon). RESULTS: Genetic results were obtained for 96.8% of trophectoderm samples versus 92.4% for both SCM techniques. The mosaicism rate was higher for SCM regardless of the technique used: 30.4% for SCM-NICS and 28.3% for SCM-Veriseq versus 14.1% for trophectoderm biopsies (P = 0.013, P = 0.031, respectively). No significant differences in diagnostic concordance were seen between the two SCM techniques (74.6% for SCM-NICS versus 72.3% for SCM-Veriseq; P = 0.861). For embryos biopsied on day 6, these rates reached 92.0% and 86.5%, respectively. On reanalysing trophectoderm-aneuploid embryos, the discrepancies were shown to be due to maternal DNA contamination (55.6%; 5/9), embryo mosaicism (22.2%; 2/9) and low resolution in SCM-NICS (11.1%; 1/9) and in both SCM techniques (11.1%; 1/9). CONCLUSIONS: This is the first study evaluating the consistency of different chromosomal analysis techniques for niPGT-A. In conclusion, the diagnostic concordance between PGT-A and niPGT-A seems independent of the technique used. Optimization of culture conditions and medium retrieval provides a potential target to improve the reliability of niPGT-A.

Effect of ovarian stimulation on embryo aneuploidy and mosaicism rate.

There is a high incidence of chromosome abnormalities in human embryos that leads to a failed IVF cycle. Different studies have shown that maternal age is the determining factor in the appearance of chromosomal alterations in the embryo. However, the possible influence of ovarian stimulation on oocyte and embryo aneuploidies and mosaicism is controversial. A retrospective study was carried out in which 835 embryos from 280 couples undergoing reproductive treatment using their oocytes were chromosomally analyzed. A binary logistic regression analysis was performed to evaluate the relationship between different parameters characterizing controlled ovarian stimulation (COS) and the rate of aneuploidy and embryonic mosaicism. The embryo aneuploidy rate showed no association with the use of oral contraceptives, type, total and daily doses of gonadotropins, stimulation protocol type, and drugs used for ovulation trigger (p > 0.05). In contrast, the duration of the ovarian stimulation treatment was correlated with the aneuploidy rate: patients requiring more days of stimulation presented a lower rate of aneuploid embryos (p = 0.015). None of the variables studied showed any association with the rate of embryo mosaicism. However, the duration of COS showed association with the appearance of aneuploidy, suggesting that faster recruitment could be deleterious for those reassuming meiosis, yielding more abnormal karyotype.Abbreviations: IVF: in vitro fertilization; COS: controlled ovarian stimulation; PGT-A: preimplantation genetic test for aneuploidy; hCG: human chorionic gonadotropin; GnRH: gonadotropin-releasing hormone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; NGS: next-generation sequencing; a-CGH: comparative genomic hybridization; TUNEL: Terminal transferase dUTP Nick End Labeling; FISH: fluorescent in situ hybridization.

Expert consensus for primary management of reproductive health: a Delphi study.

BACKGROUND: The main barrier for an appropriate primary management of the reproductive health was lack of knowledge about the risk factors and prevention measures for infertility and the main recommendations was to involve primary care physicians in reproductive health. AIMS: To reach a consensus around barriers and enablers for appropriate primary management of the reproductive health. METHODS: An observational study was performed using the modified Delphi technique, from October 2017 to April 2018 in private and public assisted reproduction clinics in Spain. A questionnaire consisted of 58 items, divided into four blocks to explore consensus among a group of experts by synthesizing opinions. RESULTS: In the first Delphi round, the response rate was 50% and panelists reached a 72.4% of consensus. In second round, the response rate was 55% and panelists reached a 25% of consensus. To minimize limitations related to the use of a structured questionnaire, a space for free text responses was provided. The following items yielded unanimous agreement: "It is necessary to promote reproductive planning-not just contraception-from secondary school," "The media should not trivialize pregnancies in women aged over 50," "Postponing family formation is the main cause of the increase in assisted reproduction treatments in Spain," and "Postponing motherhood implies an inherently decreased probability of having children." CONCLUSIONS: These recommendations could set the basis for a public health action plan for primary management of reproductive health. The findings may be applicable to any country whose health services system provides primary healthcare.

Monozygotic twinning following embryo biopsy at the blastocyst stage.

OBJECTIVE: Monozygotic twinning incidence following preimplantation genetic testing in embryos at cleavage-stage does not appear to increase; however, data regarding the possible impact of the blastocyst-stage preimplantation genetic testing is lacking. We compared the incidence of monozygotic twinning in preimplantation genetic testing cycles performed at the blastocyst-stage, versus cycles without PGT, following single embryo transfer. METHODS: In this retrospective cohort study, we analyzed the incidence of twin pregnancies in patients undergoing intracytoplasmic sperm injection and blastocyst-preimplantation genetic testing (253 cycles), versus a period-matched control population of patients undergoing intracytoplasmic sperm injection and single embryo transfer without preimplantation genetic testing (606 cycles). RESULTS: The overall monozygotic twinning rate was 14/859 (1.6%) per clinical pregnancy. The incidence of zygotic splitting following intracytoplasmic sperm injection and preimplantation genetic testing was 3.5% (95% Confidence interval 1.8%-6.6%) versus 0.8% (95% Confidence interval 0.3%-1.9%) following intracytoplasmic sperm injection without preimplantation sperm injection. After adjusting for potential confounders, preimplantation genetic testing cycles were associated with an increase in the incidence of monozygotic twinning when compared to cycles without embryo biopsy (Odd ratio 3.44, 95% Confidence interval 1.05-11.27, p=0.041). CONCLUSIONS: Our findings indicate that embryo biopsy for preimplantation genetic testing performed at the blastocyst stage is associated to an increase in the incidence of monozygotic twinning. Further validation in larger sample size studies is warranted. Patients undergoing preimplantation genetic testing must receive proper counselling about the potential risks of the technique.

COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management.

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.