Embryo long-term storage does not affect assisted reproductive technologies outcome: analysis of 58,001 vitrified blastocysts over 11 years.

BACKGROUND: Recently, the potential detrimental effect that the duration of storage time may have on vitrified samples has raised some concerns, especially when some studies found an association between cryostorage length and decreased clinical results. OBJECTIVE: This study aimed to evaluate the effects of the storage time length of day-5 vitrified blastocysts in 2 study groups: freeze-all cycles and nonelective frozen embryo transfers. STUDY DESIGN: This was a retrospective study that included 58,001 vitrified/warmed day-5 blastocysts from 2 different populations, according to the reason for frozen embryo transfer. Elective frozen embryo transfer comprised freeze-all cycles (N=16,615 blastocysts and 16,615 patients) in which only single embryo transfers and only the first frozen embryo transfer were included. The nonelective frozen embryo transfer group included 41,386 embryos from 25,571 patients where frozen embryo transfer took place using supernumerary embryos after fresh embryo transfer. All the possible frozen embryo transfers were included. Both single embryo transfer and double embryo transfers were included. Donor and autologous oocytes were used. The period covered by this study was 11 years. The blastocyst sample was clustered into deciles, which provided specific storage duration categories. The main outcome was the live birth rate, and secondary outcomes were embryo survival, miscarriage, and clinical and ongoing pregnancy rates according to storage duration. The impact of storage time was assessed by univariable analyses in both groups. The comparison was made between each decile and the last one. A multivariable logistic regression analysis was conducted, including the variables with significant association found in the univariate analysis. Student t test and chi-square tests, or an analysis of variance, were used wherever appropriate. P<.05 was considered statistically significant. RESULTS: There were statistical differences in baseline characteristics of patients included in the study groups. Storage durations ranged from ≤0.67 to ≥4.34 and from ≤1.8 to ≥34.81 months in freeze-all and nonelective frozen embryo transfer, respectively. Embryo survival did not show statistical differences across the categories of storage time in freeze-all and nonelective frozen embryo transfer groups. Statistical differences were found for the live birth rate across some, but not all, the subgroups of storage duration. The multivariable analysis showed no association between storage time and the live birth rate in both groups (nonsignificant). Blastocyst quality, body mass index, number of retrieved oocytes, endometrial preparation, male factor, and uterine factor were related to the drop in the live birth rate in the freeze-all group (P<.05). In the nonelective frozen embryo transfer group, the variables that showed significant association with the live birth rate were age at retrieval and frozen embryo transfer, type of frozen embryo transfer (single embryo transfer or double embryo transfers), number of retrieved oocytes, body mass index, endometrial preparation, origin of sperm sample, and female factor. CONCLUSION: This large study demonstrated no association between storage time and clinical outcome. Other variables, such as the patient's age, embryo quality, body mass index, and etiology, are somewhat responsible for impacting the outcome. This provides evidence for the safety of embryo vitrification, even after long storage periods. This is reassuring for both in vitro fertilization practitioners and patients undergoing frozen embryo transfer of either elective or nonelective embryos.

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.

Shared IVF among female couples: clinical outcomes of the Reception of Oocytes from the Partner (ROPA) method.

RESEARCH QUESTION: What is the population undergoing the ROPA (Reception of Oocytes from Partner) method and what are the outcomes of the technique? DESIGN: Case series of all ROPA treatments carried out between 2011 and 2020 in 18 fertility clinics in Spain. Demographic characteristics, cycle features, laboratory and clinical outcomes, and the intentions regarding the disposition of surplus embryos were analysed. RESULTS: Donor patients were on average 3.5 years younger than recipients (P = 0.001). No significant differences were found in body mass index or anti-Müllerian hormone. In 13% of cases, fertility issues were found: poor ovarian reserve (6.8%); endometriosis (2.9%); and polycystic ovary syndrome (2.2%). Including cases of advanced age (38 years old or older), more than one-half of couples (53.6%) had some condition that could affect fertility. Mean number of mature oocytes per cycle was 10 (+/- 5.7), and fertilization rate was 74.5% (+/- 18.8). Mean number of viable embryos was 3.2 (+/- 1.5). Surplus embryos were cryopreserved in 50.4% of cycles. Outcomes after embryo transfers from ROPA, and subsequent frozen cycles were as follows: positive pregnancy test (61.0%), clinical pregnancy (54.1%) and miscarriage rate (16.1%). Other outcomes were live birth rate per embryo transfer (44.7%); multiple pregnancy rate (5.4%); per cumulative ROPA cycle (48.6%); and per couple (61.6%). CONCLUSION: The outcomes of the ROPA method are reassuring. About one-half of the ROPA cycles resulted in a live birth and one-quarter of the cycles had surplus embryos after achieving a live birth. Main neonatal outcomes were also reassuring.

Female couples undergoing assisted reproduction - choices and the importance of pregnancy and genetics.

OBJECTIVE: To evaluate female couples' reproductive choices, the importance given to genetics and pregnancy and their expectations regarding mother-child relationship. METHODS: Observational study based on an anonymous survey applied to 217 patients during 2021. The survey was given to female couples under reproductive treatment in a private fertility clinic. The outcomes were divided into 3 main groups: the choice of their reproductive treatment, motherhood and biological links, and their plans for future reproductive treatments. RESULTS: Most patients found it easy to choose their treatments and roles. The choice was mainly driven by success rates, costs, and simplicity, except for ROPA for which sharing biological motherhood was the main reason. Most couples consider genetics and pregnancy important but, in the end, they believe they will have a similar connection to their child, regardless of the role played. In the future, some couples consider doing the same treatment while others consider inverting roles. CONCLUSIONS: Most female couples have no difficulty when it comes to choosing a reproductive treatment or role to play, mainly based on costs, success rates and the possibility of sharing biological motherhood with the ROPA method. These patients give great importance to genetics and pregnancy, but they expect a similar connection to their child regardless of the type of treatment and the roles played.

The combined effect of BMI and age on ART outcomes.

STUDY QUESTION: For a woman with infertility and overweight/obesity, can infertility treatment be postponed to first promote weight loss? SUMMARY ANSWER: Advice regarding a delay in IVF treatment to optimize female weight should consider female age, particularly in women over 38 years for whom only substantial weight loss in a short period of time (3 months) seems to provide any benefit. WHAT IS KNOWN ALREADY: Body weight excess and advanced age are both common findings in infertile patients, creating the dilemma of whether to promote weight loss first or proceed to fertility treatment immediately. Despite their known impact on fertility, studies assessing the combined effect of female age and BMI on cumulative live birth rates (CLBRs) are still scarce and conflicting. STUDY DESIGN, SIZE, DURATION: We performed a multicentre retrospective cohort study including 14 213 patients undergoing their first IVF/ICSI cycle with autologous oocytes and subsequent embryo transfers, between January 2013 and February 2018 in 18 centres of a multinational private fertility clinic. BMI was subdivided into the following subgroups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥30.0 kg/m2). PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome was CLBR. The secondary outcome was time to pregnancy. To assess the influence of female age and BMI on CLBR, two multivariable regression models were developed with BMI being added in the models as either an ordinal categorical variable (Model 1) or a continuous variable (Model 2) using the best-fitting fractional polynomials. CLBR was estimated over 1-year periods (Model 1) and shorter timeframes of 3 months (Model 2). We then compared the predicted CLBRs according to BMI and age. MAIN RESULTS AND THE ROLE OF CHANCE: When compared to normal weight, CLBRs were lower in women who were overweight (adjusted odds ratio (aOR) 0.86, 95% CI 0.77-0.96) and obese (aOR 0.74, 95% CI 0.62-0.87). A reduction of BMI within 1 year, from obesity to overweight or overweight to normal weight would be potentially beneficial up to 35 years old, while only a substantial reduction (i.e. from obesity to normal BMI) would be potentially beneficial in women aged 36-38 years. Above 38 years of age, even considerable weight loss did not compensate for the effect of age over a 1-year span but may be beneficial in shorter time frames. In a timeframe of 3 months, there is a potential benefit in CLBR if there is a loss of 1 kg/m2 in BMI for women up to 33.25 years and 2 kg/m2 in women aged 33.50-35.50 years. Older women would require more challenging weight loss to achieve clinical benefit, specifically 3 kg/m2 in women aged 35.75-37.25 years old, 4 kg/m2 in women aged 37.50-39.00 years old, and 5 kg/m2 or more in women over 39.25 years old. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design and lower number of women in the extreme BMI categories. The actual effect of individual weight loss on patient outcomes was also not evaluated, as this was a retrospective interpatient comparison to estimate the combined effect of weight loss and ageing in a fixed period on CLBR. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that there is potential benefit in weight loss strategies within 1 year prior to ART, particularly in women under 35 years with BMI ≥25 kg/m2. For those over 35 years of age, weight loss should be considerable or occur in a shorter timeframe to avoid the negative effect of advancing female age on CLBR. A tailored approach for weight loss, according to age, might be the best course of action. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. All authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: N/A.

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.

Serum progesterone concentrations are reduced in obese women on the day of embryo transfer.

RESEARCH QUESTION: Does serum progesterone concentration vary on the day of embryo transfer according to female body mass index (BMI)? DESIGN: Retrospective analysis including 3210 infertile patients undergoing an embryo transfer in the context of an artificial endometrial preparation cycle with sequential administration of oestrogens and micronized vaginal progesterone (MVP) (400 mg/12 h). Serum progesterone was measured on the day of embryo transfer, 6 ± 2 h after last MVP administration. Serum progesterone concentrations were subdivided into optimal (≥9.2 ng/ml) or suboptimal (<9.2 ng/ml) concentrations, and the cut-off point was defined according to our previous results. The primary objective was the correlation between progesterone concentrations on the day of embryo transfer and patient BMI, as a continuous variable and according to four ranges (underweight: <18.5 kg/m2; normal weight: 18.5-24.9 kg/m2; overweight: 25-29.9 kg/m2; and obesity: ≥30 kg/m2), according to the World Health Organization classification. Secondary objectives included the evaluation of reproductive outcome according to patient BMI and progesterone concentrations on the day of embryo transfer. RESULTS: Mean serum progesterone concentrations and the ratio of patients with progesterone concentrations above the cut-off point of 9.2 ng/ml fell progressively as BMI increased. Overweight and obese patients had lower mean serum progesterone concentrations than underweight and normal weight women (P < 0.001). A trend was observed towards impaired reproductive results in obese patients with suboptimal progesterone concentrations, absent when concentrations were optimal. CONCLUSIONS: Serum progesterone concentrations on the day of embryo transfer in artificial cycles with MPV decrease as BMI increases. It is highly recommended that serum progesterone concentrations are moitored to ensure optimal concentrations and reproductive outcomes.

Similar reproductive outcomes between lesbian-shared IVF (ROPA) and IVF with autologous oocytes.

PURPOSE: To compare reproductive outcomes of the ROPA method (reception of oocytes from partner) to IVF with autologous oocytes. To study the impact of the absence of a genetic link between the embryo and its recipient in reproductive outcomes. METHODS: Retrospective multicentric cohort study performed from January 2011 to December 2020 in 18 fertility clinics in Spain. A total of 99 ROPA (73 couples) and 2929 non-ROPA cycles (2334 couples or single patients) of women younger than 38 years old with no known female fertility disorder were included. Clinical outcomes were compared between both groups and included positive pregnancy test, clinical pregnancy, miscarriage, ectopic pregnancy, pre-term birth, live birth, weeks of gestation at birth, and newborn weight at birth. RESULTS: No differences were found between groups in clinical outcomes. The total clinical pregnancy rates per embryo transfer were 57% and 50.2% (p = 0.15) and the live-birth rates were 46.1% and 40.9% (p = 0.14) for the ROPA and non-ROPA groups, respectively. When adjusted to age and BMI of donors and recipients, there were also no differences in live-birth rates between both groups. The cumulative live-birth rate per ROPA cycle was 73.7% and the cumulative live-birth rate per couple was 78.3%. CONCLUSION: Clinical outcomes following the ROPA method and IVF with autologous oocytes were found to be similar. These findings suggest no impact of the absence of genetic ties between the embryo and the uterus on reproductive treatments' outcomes. Data regarding the outcomes of the ROPA method are reassuring.

BMI and miscarriage after IVF.

PURPOSE OF REVIEW: To summarize recent findings related to the risk of miscarriage in women with elevated BMI undergoing IVF, and the mechanisms involved in said risk. RECENT FINDINGS: Miscarriage rates are increased in overweight and obese women in both natural and assisted reproduction. Oocyte and embryo quality assessed according to classic morphological static parameters does not seem to be affected by excessive female body weight. Despite the initial lack of consensus between studies regarding embryo morphokinetics in obese women, blastocyst formation and quality have recently been shown to be similar across BMI groups, even in the case of euploid embryos. However, some metabolomic differences have been described in oocytes and embryos from obese women, thus pointing to a functional alteration. In women with elevated BMI, the percentage of aneuploid embryos is similar to that of normal weight women, and rates of miscarriage are higher, despite the transfer of euploid embryos. Therefore, the origin of the increased pregnancy loss rate after IVF in these women may be related to metabolomic, epigenetic or mitochondrial oocyte and embryo disturbances, or to the abnormal endocrine, metabolic and inflammatory uterine environment induced by obesity, which seems to be also responsible for other numerous complications during pregnancy and the in-utero fetal programming of postnatal diseases. A displacement of the window of implantation in obese women undergoing artificial endometrial preparation has recently been described and may be related to the poorer embryo implantation rates and increased risk of miscarriage observed following fresh and frozen embryo transfers with autologous oocytes, and with donated ova in recipients with extremely high BMI. SUMMARY: Female obesity is related to poorer outcome in natural and assisted conception, including an increased risk of miscarriage. Embryo morphology, assessed by conventional methods or by morphokinetics, does not seem to be affected by excess weight, with similar blastocyst formation and quality than normal weight women reported in IVF cycles. Embryo aneuploidy is not increased, and higher miscarriages rates are seen after euploid embryo transfer in obese women. Disturbances of the uterus or its environment induced by female obesity seem to be the most likely cause of the increased risk of miscarriage, although metabolomic, epigenetic or mitochondrial oocyte and embryo dysfunction cannot be ruled out as cannot congenital anomalies. In the context of all the above, weight reduction before pregnancy should be advised in obese women trying to become pregnant.

ROPA - Lesbian shared in vitro fertilization - Ethical aspects.

Recently, a technique of assisted reproduction was developed to allow lesbian women to share biological motherhood of their offspring - the ROPA method (in Spanish - Recepción de Ovocitos de Pareja; in English - Reception of Partner's Oocytes), also known as lesbian shared in vitro fertilization. One mother provides the oocytes (genetic mother) and the other receives the embryo and gets pregnant (gestational mother). As for most issues related to medically assisted reproduction, this technique raises a lot of ethical questions in respect to patients, future offspring, gametes, and embryos. Furthermore, the fact that it is directed to homosexual women poses its own issues, both biological and social in nature. This is a state-of-the-art review of the main ethical dilemmas related to this technique, primarily focusing on the basic principles of bioethics, but also specific concerns directly related to this kind of treatments.

Blastocyst formation is similar in obese and normal weight women: a morphokinetic study.

STUDY QUESTION: Does the embryo cleavage pattern and rate of blastocyst formation differ between normal weight and obese women undergoing IVF? SUMMARY ANSWER: Embryo morphokinetic development, final blastocyst formation rate and blastocyst morphology do not differ between obese and normal weight women. WHAT IS KNOWN ALREADY: Female obesity has been related to impaired IVF outcomes. Although the mechanisms responsible for this detrimental effect are thought to include impaired oocyte and embryo quality and reduced endometrial receptivity, they are yet to be confirmed. Embryo quality has been commonly assessed using static morphological criteria. Only three studies have analysed the progress of embryos up to the blastocyst stage in women with elevated BMI, but they have used small samples of patients or have obtained contradictory results. STUDY DESIGN, SIZE, DURATION: This retrospective, cohort study, was performed from January 2016 to May 2020. A total of 3316 ICSI cycles from 2822 women were included, of which 1251 cycles were part of a preimplantation genetic testing programme. In total, 17 848 embryos were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study reports on the IVF cycles of infertile women, with a known BMI, who underwent ICSI and whose embryos were grown until the fifth/sixth day of development in a time-lapse system. Patients were grouped as follows. Underweight was defined as a BMI <18.5 kg/m2; normal weight was a BMI of 18.5-24.9 kg/m2; overweight was a BMI of 25-29.9 kg/m2; and obesity was a BMI of ≥30 kg/m2. Embryo development was assessed on an external computer with analysis software. MAIN RESULTS AND THE ROLE OF CHANCE: Despite an initial slower pattern of embryo development, the blastocyst formation rate on day 5 or on day 5 plus day 6 did not differ in obese women with respect to the other three BMI groups. Moreover, based on the evaluation of inner cell mass and the trophectoderm on both days of blastocyst development, embryo quality was similar across the BMI groups, as were the pattern of development and arrest up to blastocyst formation and the distribution of the categories of full, expanded and hatching blastocysts. LIMITATIONS, REASONS FOR CAUTION: Limitations include the retrospective analysis of data, the use of BMI as the only parameter to define normal/abnormal female body weight, and the lack of complete information about clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst formation and embryo morphokinetics are not affected by female obesity, and the poorer IVF outcomes described for such women are probably due to deficient endometrial receptivity. The role of endometrial progesterone exposure on the day of embryo transfer should be analysed in future studies as a possible determining factor. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used and there are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Obesity Affects Endometrial Receptivity by Displacing the Window of Implantation.

Our aim was to determine prospectively whether increased body mass index (BMI) affects endometrial receptivity through displacement of the window of implantation (dWOI) using the endometrial receptivity analysis (ERA), and whether this effect is BMI-dependent. We recruited a population of 170 infertile women with a normal uterus and no clinical history of recurrent miscarriage or implantation failure. These women were divided into four groups according to BMI: normal weight (18.5-24.9 kg/m2; n = 44), overweight (25-29.9 kg/m2; n = 29), class I obese (30.0-34.9 kg/m2; n = 54), and class II and III obese (> 35 kg/m2; n = 43). We also assigned the patients to one of two larger BMI cohorts: non-obese (normal weight and overweight; n = 73) and obese (class I, II, and III obese; n = 97). We compared analytical and clinical data and dWOI in these categories, finding significant metabolic differences in glycemia, TSH, insulin, HDL cholesterol, LDL cholesterol, triglycerides, and systolic and diastolic blood pressure among the different BMI groups. One-day dWOI increased significantly with BMI, and significant differences were observed in the non-obese versus obese categories (9.7% vs 25.3 %, respectively (p = 0.02)). dWOI was most pronounced in patients with class II-III obesity. In addition, displacement was longer as BMI increased since ERA revealed a higher proportion of displacements of 1 day than of 12 h and showed they were predominantly pre-receptive. In conclusion, obesity has a negative effect on endometrial receptivity through delaying of the WOI, which increases in function of BMI as well as the metabolic disturbances of the patient.

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.

Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone.

STUDY QUESTION: Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced? SUMMARY ANSWER: Serum P levels <8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles. WHAT IS KNOWN ALREADY: We previously found that serum P levels <9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin. STUDY DESIGN, SIZE, DURATION: This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET. MAIN RESULTS AND THE ROLE OF CHANCE: Women with serum P levels <8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P < 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels <8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION: Only women with MVP were included. Extrapolation to other P administration forms needs to be validated. WIDER IMPLICATIONS OF THE FINDINGS: This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: NCT03272412.

Female obesity increases the risk of miscarriage of euploid embryos.

OBJECTIVE: To determine whether female body mass index (BMI) is associated with an increased risk of miscarriage after euploid embryo transfer. DESIGN: A retrospective, observational, multicenter cohort study. SETTING: University-affiliated in vitro fertilization center. PATIENT(S): In this study, 3,480 cycles of in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) in the blastocyst stage and euploid embryo transfer were divided into four groups according to patient BMI. INTERVENTION(S): In vitro fertilization with PGT-A. MAIN OUTCOME MEASURE(S): The primary outcome was the miscarriage rate, which included both biochemical and clinical miscarriages. Secondary outcomes were implantation, pregnancy, clinical pregnancy, and live birth rates. RESULT(S): Cycles were divided into four groups according to BMI (kg/m2): underweight (<18.5; n = 155), normal weight (18.5-24.9; n = 2,549), overweight (25-29.9; n = 591), and obese (≥30; n = 185). The number of PGT-A cycles per patient was similar in the four groups. Fertilization rate, day of embryo biopsy, technique of chromosomal analysis, number of euploid embryos, number of transferred embryos, and method of endometrial preparation for embryo transfer were similar in the four BMI groups. Miscarriage rates were significantly higher in women with obesity compared to women with normal weight, mainly due to a significant increase in the clinical miscarriage rates. Live birth rates also were lower in women with obesity. Obesity in women and day 6 trophectoderm biopsy were found to influence the reduced live birth rate. CONCLUSION(S): Women with obesity experience a higher rate of miscarriage after euploid embryo transfer than women with a normal weight, suggesting that other mechanisms than aneuploidy are responsible for this outcome.

Time of morulation and trophectoderm quality are predictors of a live birth after euploid blastocyst transfer: a multicenter study.

OBJECTIVE: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET). DESIGN: Observational cohort study conducted in two phases: training and validation. SETTING: Private in vitro fertilization centers. PATIENT(S): Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively. INTERVENTION(S): Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set. MAIN OUTCOME MEASURE(S): Live births per SET. RESULT(S): The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51). CONCLUSION(S): Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation.

Ovarian stimulation for oocyte vitrification does not modify disease-free survival and overall survival rates in patients with early breast cancer.

RESEARCH QUESTION: Does ovarian stimulation for oocyte vitrification affect disease-free survival and overall survival rates in women with early breast cancer? DESIGN: This cohort study included 259 patients with early breast cancer; 148 patients underwent ovarian stimulation, whereas 111 patients did not. Patients were treated between January 2008 and December 2016. To calculate the disease-free survival time and overall survival rate, the time of definitive surgery was defined as the starting point. The follow-up was conducted up to 5 years. RESULTS: Exposed and non-exposed groups were comparable in tumour, node and metastases classification, Nottingham grade, hormonal receptor status, tumour molecular phenotype, histology and pathology stage. The exposed group was younger than the non-exposed. Recurrences occurred in 9/148 women (6.1%) in the exposed group and 15/111 women (13.5%) in the non-exposed group, with no significant difference. The mean disease-free survival time was 63.9 months (95% confidence interval [CI]: 61.5-66.4) in the exposed group and 60.6 months (95% CI: 56.9-64.2) in the non-exposed, with no significant difference (log-rank [Mantel-Cox] test). Overall survival rates were comparable; 2/148 (1.4%) and 4/111 (3.6%) patients died, in exposed and non-exposed groups, respectively, during the period analysed. Mean overall survival times were 67.2 months (95% CI: 66.2-68.2) in the exposed group and 65.9 months (95% CI: 64.0-67.9) in the unexposed, with no significant difference (log-rank [Mantel-Cox] test). CONCLUSIONS: This study suggests that ovarian stimulation in patients with early-stage breast cancer is safe in the long term.