Intra-patient analysis of individual weight gain or loss between IVF cycles: cycle now and transfer later.

STUDY QUESTION: What is the impact of clinically significant weight change on outcomes related to IVF cycle performance? SUMMARY ANSWER: While individual weight loss did not significantly impact ovarian response to stimulation or other cycle outcome parameters in our study, some positive associations were found for individual weight gain. WHAT IS KNOWN ALREADY: The role of weight-change in patients undergoing IVF has been largely studied by comparing weight loss in different cohorts of patients stratified by a static BMI. Specifically, obesity has been extensively studied in relation to its negative effects on assisted or unassisted conception outcomes and ovulatory function. Previous research has shown conflicting results, while BMI, which is commonly used as a marker of obesity, may not accurately reflect the underlying factors affecting fertility in obese patients. STUDY DESIGN, SIZE, DURATION: This study utilized a retrospective within-patient repeated measurement analysis design to assess the impact of weight change on IVF outcomes in cycles where all embryos were cryopreserved at the blastocyst stage for transfer at a later date. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an academically affiliated fertility center. The data included 961 women who underwent at least two IVF cycles between December 2014 and June 2020, with documented short-term weight gain (n = 607) or weight loss (n = 354) within 1 year from their initial IVF cycle. Multivariable generalized estimating equations (GEE) and generalized linear mixed models (GLMM) were employed to assess associations between weight change and outcomes across cycles. MAIN RESULTS AND THE ROLE OF CHANCE: The multivariable models indicated that weight loss did not show any significant associations with the numbers of oocytes retrieved, or mature oocytes, the fertilization rate or the blastulation rate. However, weight gain demonstrated a minor positive association with the number of oocytes retrieved in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.01) and GLMM models (0.01, 95% CI: 0.01-0.00). There was also a potential increase in the fertilization rate with weight gain, as indicated by a positive coefficient in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.02) and GLMM models (coefficient: 0.01, 95% CI: 0.00-0.01). However, the association between weight gain and the embryo blastulation rate was not statistically significant in any model. LIMITATIONS, REASONS FOR CAUTION: This study focused on cycle performance parameters instead of reproductive outcomes, which restricted our ability to evaluate the impact of weight change on cumulative live birth rates. Additionally, the study did not account for variables such as stimulation protocols, potentially introducing confounding factors and limiting the generalizability of the results. WIDER IMPLICATIONS OF THE FINDINGS: Although obesity is associated with adverse obstetrical risks, there is less evidence of adverse reproductive outcomes in IVF cycles. We therefore recommend that an IVF cycle should not be delayed due to weight, so that the patient is not adversely affected by increasing age. The IVF cycle should aim to freeze all embryos, so that embryo transfer can then occur after weight loss, so as to limit the recognized obstetrical risks. STUDY FUNDING/COMPETING INTEREST(S): The study was not funded and there were no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Do sperm factors influence embryonic aneuploidy? Long live the oocyte.

STUDY QUESTION: What is the impact of male age- and sperm-related factors on embryonic aneuploidy? SUMMARY ANSWER: Using a 3-fold analysis framework encompassing patient-level, embryo-level, and matching analysis, we found no clinically significant interactions between male age and sperm quality with embryo ploidy. WHAT IS KNOWN ALREADY: While the effect of maternal age on embryo chromosomal aneuploidy is well-established, the impact of male age and sperm quality on ploidy is less well-defined. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analyzed autologous preimplantation genetic testing for aneuploidy (PGT-A) and frozen embryo transfer cycles from December 2014 to June 2021. The study involved 11 087 cycles from 8484 patients, with a total of 35 797 embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: The aneuploidy rate, calculated as the ratio of aneuploid blastocysts to the total number of blastocysts biopsied in a single treatment cycle, was evaluated. In the embryo-level analysis, the main outcome measure was the ploidy state of the embryos. The study employed a multifaceted analytical approach that included a patient-level analysis using generalized linear mixed models, an embryo-level analysis focusing on chromosomal ploidy, and a propensity score matching analysis contrasting groups with distinct ploidy rates (0% and 100%). There were no interventions as this was an observational study of PGT-A cycles. MAIN RESULTS AND THE ROLE OF CHANCE: No clinically relevant factors influencing ploidy rate related to male and sperm quality were revealed. In contrast, female age (coefficient = -0.053), BMI (coefficient = 0.003), prior ART cycle (coefficient = -0.066), and number of oocytes retrieved (coefficient = -0.018) were identified at the patient level. Embryo analysis identified age (coefficient = -0.1244) and ICSI usage (coefficient = -0.0129) as significant factors. Despite these, no significant interactions between male and female assessed factors on the ploidy rate emerged. Propensity score matching between maximal (100% vs 0%) euploid rates did not reveal significant differences of influence by male age and sperm quality. LIMITATIONS, REASONS FOR CAUTION: The focus on patients having blastocyst biopsy for PGT-A may not reflect the broader IVF population. Other semen quality parameters like DNA fragmentation were not included. Exclusion of embryo mosaicism from the analysis could affect aneuploidy rate interpretations. There may also be unmeasured influences like lifestyle or environmental factors. WIDER IMPLICATIONS OF THE FINDINGS: Male age and sperm quality parameters were consistent across both maximal and minimal ploidy rate comparisons. No significant clinical characteristics related to the factors assessed for the male-influenced blastocyst ploidy status, confirming the dominancy of the oocyte and female age. STUDY FUNDING/COMPETING INTEREST(S): The study was not funded. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Intrapartum fever complicated with maternal bacteremia: prevalence, bacteriology, and risk factors.

PURPOSE: To assess the prevalence, microbial profile, and clinical risk factors of maternal bacteremia associated with intrapartum fever (IPF). METHODS: A retrospective cohort study, in a single tertiary university-affiliated medical center between 2012 and 2018. Demographic and labor characteristics of women, who delivered at term (37+0/7-41+6/7) and developed bacteremia following IPF were compared to a control group of women with IPF but without bacteremia. RESULTS: During the study period there were 86,590 deliveries in our center. Of them, 2074 women (2.4%) were diagnosed with IPF, of them, for 2052 women (98.93%) the blood maternal cultures were available. In 26 patients (1.25%) maternal bacteremia was diagnosed. A lower rate of epidural anesthesia (84.6% vs 95.9%, p = 0.02) and a higher rate of antibiotics prophylaxis treatment prior to the onset of fever (30.8%.vs 12.1%, p = 0.006) were observed in patients who developed maternal bacteremia in comparison to those who have not. Maternal hyperpyrexia developed after initiation of antibiotics or without epidural anesthesia remained significantly associated with maternal bacteremia after applying a multivariate analysis, (Odds Ratio 3.14 95% CI 1.27-7.14, p = 0.009; 4.76 95% CI 1.35-12.5, p = 0.006; respectively). CONCLUSION: Maternal fever developing after initiation of antibiotics or without epidural is associated with maternal bacteremia.

Acceptance of genetic editing and of whole genome sequencing of human embryos by patients with infertility before and after the onset of the COVID-19 pandemic.

RESEARCH QUESTION: Has acceptance of heritable genome editing (HGE) and whole genome sequencing for preimplantation genetic testing (PGT-WGS) of human embryos changed after the onset of COVID-19 among infertility patients? DESIGN: A written survey conducted between April and June 2018 and July and December 2021 among patients at a university-affiliated infertility practice. The questionnaire ascertained the acceptance of HGE for specific therapeutic or genetic 'enhancement' indications and of PGT-WGS to prevent adult disease. RESULTS: In 2021 and 2018, 172 patients and 469 patients (response rates: 90% and 91%, respectively) completed the questionnaire. In 2021, significantly more participants reported a positive attitude towards HGE, for therapeutic and enhancement indications. In 2021 compared with 2018, respondents were more likely to use HGE to have healthy children with their own gametes (85% versus 77%), to reduce disease risk for adult-onset polygenic disorders (78% versus 67%), to increase life expectancy (55% versus 40%), intelligence (34% versus 26%) and creativity (33% versus 24%). Fifteen per cent of the 2021 group reported a more positive attitude towards HGE because of COVID-19 and less than 1% a more negative attitude. In contrast, support for PGT-WGS was similar in 2021 and 2018. CONCLUSIONS: A significantly increased acceptance of HGE was observed, but not of PGT-WGS, after the onset of COVID-19. Although the pandemic may have contributed to this change, the exact reasons remain unknown and warrant further investigation. Whether increased acceptability of HGE may indicate an increase in acceptability of emerging biomedical technologies in general needs further investigation.

ART outcomes in lean compared to obese phenotypes of polycystic ovarian syndrome.

RESEARCH QUESTION: To investigate differences in reproductive outcomes among IVF patients with lean compared to obese polycystic ovarian syndrome (PCOS) phenotypes. DESIGN: A retrospective cohort study of patients with PCOS who underwent IVF in a single, academically affiliated infertility center in the USA between December 2014 and July 2020. The diagnosis of PCOS was assigned based on Rotterdam criteria. Patients were designated as lean (< 25) or overweight/obese (≥ 25) PCOS phenotype based on BMI (kg/m2) at cycle start. Baseline clinical and endocrinologic laboratory panel, cycle characteristics, and reproductive outcomes were analyzed. The cumulative live birth rate included up to 6 consecutives cycles. A Cox proportional hazards model and Kaplan-Meier curve for estimating live birth rates were used to compare the two phenotypes. RESULTS: A total of 1395 patients who underwent 2348 IVF cycles were included. The mean (SD) BMI was 22.7 (2.4) in the lean and 33.8 (6.0) in the obese group (p < 0.001). A number of endocrinological parameters were similar between lean and obese phenotypes: total testosterone 30.8 ng/dl (19.5) vs 34.1 (21.9), p > 0.02 and pre-cycle hemoglobin A1C 5.33% (0.38) vs 5.51% (0.51) p > 0.001, respectively. The CLBR was higher in those with a lean PCOS phenotype: 61.7% (373/604) vs 54.0% (764/1414) respectively. Miscarriage rates were significantly higher for O-PCOS patients (19.7% (214/1084) vs 14.5% (82/563) p < 0.001) and the rate of aneuploids was similar (43.5%, 43.8%, p = 0.8). A Kaplan-Meier curve estimating the proportion of patients with a live birth was higher in the lean group (log-rank test p = 0.013). After adjusting for potential confounders, the lean phenotype was associated with an increased hazard ratio for live birth: HR = 1.38 p < 0.001. CONCLUSIONS: Lean PCOS phenotype is associated with a significantly higher CLBR compared to their obese counterparts. Miscarriage rates were significantly higher among obese patients, despite comparable pre-cycle HBA1C and similar aneuploidy rates in patients who underwent PGT-A.

The association between a carrier state of FMR1 premutation and numeric sex chromosome variations.

PURPOSE: Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations. METHODS: A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes. RESULTS: A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either. CONCLUSIONS: Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve.

A decision tree analysis applied to women aged 43-45: who should be referred for ovum donation?

RESEARCH QUESTION: In women at the advanced age of 43-45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes? DESIGN: A retrospective cohort study was conducted at a university hospital reproductive centre. The computerized database of 394 women aged 43-45 years undergoing 1528 non-donor IVF or intracytoplasmic sperm injection cycles between 2010 and 2019 was analysed. A decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes. RESULTS: The cumulative clinical pregnancy rate was 15.0% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women who should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and body mass index. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did. CONCLUSIONS: Women over 43.5 years old with fewer than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible.

The impact of fragile X premutation carrier status on embryo morphokinetic development.

RESEARCH QUESTION: Does inheritance of the fragile X mental retardation 1 (FMR1) premutation allele affect embryo morphokinetic development? DESIGN: A retrospective cohort analysis of 529 embryos from 126 IVF cycles of 39 FMR1 premutation female carriers undergoing preimplantation genetic testing for monogenic/single gene defects (PGT-M). Morphological and morphokinetic parameters obtained using a time-lapse monitoring system were compared between embryos that inherited the FMR1 premutation allele (FMR1 group, n = 271) and those who received the normal allele (normal group, n = 258). The following embryo outcome measures were compared: morphokinetic parameters up to day 3, start of blastulation time (tSB) for day 5 embryos and the rate of top-quality embryos on days 3 and 5. RESULTS: No differences were found in morphokinetic parameters between the groups from the time of intracytoplasmic sperm injection (ICSI) until a biopsy on day 3. The blastulation rate in the two groups was comparable. However, the start of blastulation was delayed in FMR1 embryos compared to that in the genetically normal embryos (median tSB: 104.2 h [99.3-110.3] versus 101.6 h [94.5-106.7], P = 0.01). In addition, the rate of top-quality FMR1 embryos was lower than that of genetically normal embryos (25.6% versus 38.8%, P = 0.04). CONCLUSION: Embryos that inherit the FMR1 premutation allele are of lower quality at the blastocyst stage compared with those that do not inherit the mutated allele.

Reproductive Outcomes and Overall Prognosis of Women with Asherman's Syndrome Undergoing IVF.

STUDY OBJECTIVE: To evaluate the impact of Asherman syndrome (AS) following hysteroscopic adhesiolysis on reproductive outcomes and the time to achieve pregnancy in women with infertility undergoing in vitro fertilization (IVF) treatment. DESIGN: Case-control study. SETTING: Tertiary university-affiliated medical center. PATIENTS: Fifty-one infertile women who were treated for AS and underwent IVF (study group) matched for age and etiology of infertility with non-AS controls at a 1:1 ratio. INTERVENTIONS: Medical records search, chart review, and phone survey were used to assess reproductive outcomes. MEASUREMENTS AND MAIN RESULTS: A multivariate logistic regression analyses was used to assess live birth, accounting for patient age at stimulation cycle start, parity, number of embryos transferred, and endometrial thickness. A survival analysis was performed to assess the times that had lapsed from interventions to conception. The study group of 51 women included 38 (74.5%) with moderate to severe disease. The mean number of embryo transfers per woman was similar for the study and control groups (4.9 ± 4.6 vs 6.22 ± 4.3, respectively, p = .78). The controls had a significantly higher mean endometrial thickness before embryo transfer (8.7 ± 1.8 mm vs 6.95 ± 1.7 mm, p = .001). The overall time to achieve live birth was significantly longer in women with AS (p = .022). In a logistic regression analysis, the presence of moderate to severe AS was shown to be an independent factor for achieving a live birth (adjusted odds ratio 0.174, 95% confidence interval [CI], 0.032-0.955, p = .004). Women with AS who had live births had a significantly thicker mean endometrial thickness (8.2 ± 1.4 mm vs 6.9 ± 1.2, p = .001). CONCLUSION: Moderate and severe AS has a detrimental effect on reproductive performance in infertile women. Endometrial thickness is an important predictor for live births among women with AS who undergo IVF.

Recurrent Ovarian Torsion: Risk Factors and Predictors for Outcome of Oophoropexy.

STUDY OBJECTIVE: To identify risk factors for recurrent ovarian torsion and evaluation of the efficacy of oophoropexy techniques. DESIGN: Case control study. SETTING: Tertiary university-affiliated medical center. PATIENTS: A total of 79 women with recurrent ovarian torsion (study group) were matched with 158 women with a single episode of ovarian torsion (control group). INTERVENTIONS: Laparoscopic detorsion and oophoropexy. MEASUREMENTS AND MAIN RESULTS: Demographic data, clinical characteristics, ultrasound characteristics, surgical findings, surgical procedures, and torsion recurrence rates were analyzed and compared between the 2 groups between 2001 to 2020. RESULTS: There was an inverse association between women's age and the risk of recurrent torsion (adjusted odds ratio [aOR], 0.89; 95% confidence interval [CI], 0.83-0.96, p = .003). Moreover, in women younger than 20 years, the risk of recurrent event was substantially higher (aOR, 5.0; 95% CI, 1.56-6.15, p = .007). In addition, the absence of ovarian pathology was associated with increased risk for recurrent torsion (aOR, 14.3; 95% CI, 6.15-33.42; p <.001). Oophoropexy was performed in 46 women in the study group. The risk of recurrent torsion after oophoropexy was 30%. A long duration of pain before admission was associated with oophoropexy failure (37.5 ± 6.3 hours vs 11.7 ± 6.0 hours, p = .003). No single fixation procedure was superior to the others in terms of therapeutic success. CONCLUSION: Recurrent ovarian torsion is more common in young women with a normal-appearing ovary. Oophoropexy is a safe procedure with a risk of retorsion in 30% of the patients. We found no advantage for one fixation technique over the others.

Fertility preservation and PGT-M in women with familial adenomatous polyposis-associated desmoid tumours.

RESEARCH QUESTION: Is ovarian stimulation and pregnancy in women with familial adenomatous polyposis (FAP)-associated desmoid tumours safe? DESIGN: The study included women with FAP-associated desmoid tumours who underwent fertility treatments at the authors' tertiary medical centre between the years 2011 and 2021. Data were collected from the fertility unit's charts and from the oncological registries. The main outcome measures were the number of vitrified oocytes and embryos, and the number of live births in preimplantation genetic testing for monogenic/single gene defects (PGT-M) cycles. RESULTS: Overall, 17 women were identified suitable for this study. A total of 117 mature oocytes were vitrified for fertility preservation and 106 embryos were submitted to PGT-M. One patient returned to claim her cryopreserved oocytes, and five patients who underwent PGT-M embryo transfer reported three live births. A statistically significant decrease in selected fertility cycle parameters was observed in one woman who co-administered sorafenib (a multikinase inhibitor) during her first cycles of treatment, as the mean number of oocytes before and after was 2.7 (±1.3) versus 13.2 (±3.3) (P = 0.02), the mean number of metaphase II oocytes was 2.2 (±2.1) versus 7.7 (±2.6) (P = 0.007), and the mean number of two-pronuclei oocytes was 0.5 (±1.1) versus 3.5 (±1.7) (P = 0.09). Three patients had a median desmoid tumour growth on magnetic resonance imaging of 6.2 (2.9-7.2) cm when compared with prior ovarian stimulation imaging. CONCLUSIONS: Ovarian stimulation for women with desmoid tumours was characterized in some patients with an acceleration in tumour growth, regardless of the use of aromatase inhibitors. The use of sorafenib should be carefully considered during the course of fertility treatment.

A decision tree model for predicting live birth in FMR1 premutation carriers undergoing preimplantation genetic testing for monogenic/single gene defects.

RESEARCH QUESTION: Can patient selection for successful preimplantation genetic testing for women who are fragile X (FMR1) premutation carriers be optimized using a decision tree analysis? This decision support tool enables a comprehensive study of a set of clinical parameters and the expected outcomes. DESIGN: A retrospective case-control study analysing the results of 264 fresh and 21 frozen preimplantation genetic testing for monogenic disorders/single gene defects (PGT-M) cycles in 64 FMR1 premutation carriers. Primary outcome was live birth per cycle start. Live birth rate was calculated for the start of the ovarian stimulation cycle. Fresh and frozen embryo transfers from the same cycle were included. RESULTS: The decision tree model showed that the number of cytosine guanine (CGG) repeats was only a moderate predictor for live birth, whereas an age younger than 36 years was the best predictor for live birth, followed by a collection of 14 or more oocytes. These findings were supported by the results of the logistic regression, which found that only age and oocyte number were significantly associated with live birth (P = 0.005 and 0.017, respectively). CONCLUSIONS: The number of CGG repeats is a relatively poor predictor for live birth in PGT-M cycles. FMR1 premutation carriers are no different from non-carriers. Age is the best identifier of live birth, followed by the number of retrieved oocytes.

Maternal presentation and neonatal outcome in peripartum enterovirus infection.

AIM: Enterovirus is a common pathogen. Although mostly asymptomatic, this infection has the potential to be life-threatening in neonates. This article aims to describe the early neonatal outcomes in peripartum infection. METHODS: We performed a retrospective cohort study in a tertiary hospital between 1/2014 and 5/2019. The enterovirus infection was established by real-time polymerase chain reaction analysis. RESULTS: Out of 161 neonates tested for the enterovirus infection 13 (8%) were positive. Maternal fever was the most common sign (n = 8, 66.7%). The mean gestational age at delivery was 36 + 5 (range 30 + 5 to 40 + 6 weeks). The mean time interval from birth to neonatal manifestations of infection was 5.2 (0-9) days. The most common presenting sign in the neonates was fever (n = 8, 61.5%). All neonates required the neonatal intensive care unit. The neonatal mortality rate was 3/13 (23%). CONCLUSION: The neonatal morbidity and mortality from the enterovirus infection may have been associated with the severity of maternal presentation at the time of admission. Enterovirus real-time polymerase chain reaction analysis should be considered as part of the maternal evaluation in cases of maternal fever of unknown origin. Deferral of the induction of delivery for term pregnancies with confirmed enterovirus infections should be considered.

The Contribution of an Infectious Workup in Understanding Stillbirth.

OBJECTIVE: This study was aimed to assess the utility of diagnostic tests of maternal and fetal infection in the evaluation of stillbirth. STUDY DESIGN: A single-center retrospective study from January 2011 to December 2016 of all women presenting to the hospital with intrauterine fetal death at or after 20 weeks of gestation. Standard evaluation included review of medical records, clinical and laboratory inflammatory workup, maternal serologies, fetal autopsy, placental pathology, and fetal and placental cultures. A suspected infectious etiology was defined as meeting at least two diagnostic criteria, and only after exclusion of any other identifiable stillbirth cause. RESULTS: During the 7-year study period, 228 cases of stillbirth were diagnosed at our center. An infectious etiology was the suspected cause of stillbirth in 35 cases (15.3%). The mean gestational age of infection-related stillbirth was 28 1/7 (range: 22-37) weeks, while for a noninfectious etiology, it was 34 0/7 (range: 25-38) weeks (p = 0.005). Placental histological findings diagnostic of overt chorioamnionitis and funisitis were observed in 31 (88.5%) cases. In 16 (45.7%) cases the placental and fetal cultures were positive for the same pathogen. Serology of acute infection was positive in three (8.5%) of the cases. CONCLUSION: Maternal and fetal infectious workup is valuable in the investigation of stillbirth, particularly before 30 weeks of gestation and should be considered a part of standard evaluation.

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients.

PURPOSE: To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes. METHODS: Retrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level. RESULTS: The number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar in the letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35-60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024-1.12, P = 0.004 per 100 unit change in estradiol). CONCLUSIONS: There may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings.

Efficacy of a second external cephalic version (ECV) after a successful first external cephalic version with subsequent spontaneous reinversion to breech presentation: a retrospective cohort study.

OBJECTIVE: Determining the efficacy of performance of a second external cephalic version (ECV) following successful first ECV with subsequent spontaneous reinversion to breech presentation in reducing the rate of cesarean delivery (CD). METHODS: Data were reviewed on healthy women with fetuses in breech presentation who underwent a first ECV after 36 weeks. Routine ultrasound study was performed at 39-week gestation, and a repeat ECV procedure was performed if the fetus had reverted to non-cephalic presentation. Obstetrical outcome measures were compared between women who underwent one successful ECV between 36- and 41-week gestation in which the fetus remained in cephalic presentation until labor and those who underwent a successful first ECV after which the fetus returned to breech and a second ECV was performed. The primary outcome was the rate of secondary CD during vaginal delivery in cephalic presentation; rate of successful second ECV was the secondary outcome. RESULTS: Overall 250 women underwent one ECV attempt of which 169 (67%) were successful. Of them 28 reverted to breech presentation, all women underwent two attempts of which 21 (76%) were successful. A second successful ECV attempt was associated with a 33% incidence of a CD vs. 2.8% after one successful ECV in which the fetus remained in cephalic presentation. CONCLUSION: A second ECV after a successful first ECV with subsequent spontaneous reversion to breech presentation can be expected to be successful in 76% of cases but lead to CD in 33% of cases. Our findings can be used to support patient counseling and decision-making before second ECV attempt.

In-vitro maturation of oocytes recovered during cryopreservation of pre-pubertal girls undergoing fertility preservation.

RESEARCH QUESTION: In-vitro maturation (IVM) of oocytes recovered during ovarian tissue cryopreservation (OTC) is often practised, although it is still considered experimental. To date, only a few studies have examined the success of this maturation process in pre-menarche girls. The aim of this study was to examine the outcomes of IVM of oocytes recovered during OTC in pre-menarche patients scheduled for onco-therapy. DESIGN: A retrospective cohort study in a tertiary university-affiliated hospital. A total of 93 patients aged 0-25 years who underwent OTC as part of onco-fertility preservation between 2007 and 2019 were included in the study. Oocytes were recovered from the medium after OTC and matured over 48 h. Oocyte development and maturation rate were recorded and compared between different age groups. RESULTS: Patient's age was not correlated linearly with the total number of mature oocytes R = 0.2. The absolute maturation rate in post-menarche and pre-menarche patients differed significantly (38.0% versus 25.3%, respectively; P > 0.001), whereas the degeneration rate of the oocytes did not (39.8% versus 33.5%; P = 0.167). The pre-menarche group had significantly lower mean number of metaphase II oocytes compared with the post-menarche group (2.8 [±2.3] versus 5.6 [±4.6]; P = 0.01; 95% CI -4.62 to -0.46). Oocytes recovered from patients aged 1-5 years demonstrated low maturation rate. CONCLUSIONS: Oocytes recovered from pre-menarche girls, and especially those younger than the age of 5 years who undergo fertility preservation, have a lower chance of reaching maturity in IVM compared with older women. This may indicate a need for alternative methods for preserving fertility in these young patients.

The effects of a postmiscarriage menstrual period prior to reconceiving.

BACKGROUND: The optimal interpregnancy interval after a single pregnancy loss is controversial. It is common obstetrical practice to recommend that women who have had a miscarriage in the first trimester of pregnancy should wait for 1 or more menstrual cycles before attempting to conceive again. OBJECTIVE: This study aimed to assess whether conception before the first menstrual period after a spontaneous pregnancy loss is associated with a risk of repeat miscarriage or adverse perinatal outcomes. STUDY DESIGN: This retrospective cohort study included 107 women who had a spontaneous miscarriage in the first trimester of pregnancy followed by a subsequent pregnancy with an interpregnancy interval of <12 weeks. All miscarriages had ended in either spontaneous expulsion of the products of conception or medical or surgical evacuation of the uterus. The perinatal outcome measures of 57 women who conceived after the first menstrual period following a spontaneous miscarriage were compared with perinatal outcome measures of 50 women who conceived before the first menstrual period following a spontaneous miscarriage. The primary outcome was rate of pregnancy loss, and the secondary outcomes were gestational age at delivery and birthweight. RESULTS: The rate of recurrent miscarriage was 10.4% for women who conceived before the first menstrual period following a spontaneous miscarriage and 15.8% for those who conceived after (P=.604). There were no differences in the gestational age at delivery (38.9 vs 38.7 weeks; P=.66) or the birthweight (3347±173 vs 3412±156 g; P=.5) between the 2 groups. Other outcomes, such as mode of delivery and 5-minute Apgar score, were also similar for both groups. A multiple logistic regression analysis confirmed that conception before the first menstrual period following a spontaneous miscarriage was not associated with a higher incidence of subsequent miscarriage (odds ratio, 1.74; P=.46) or any other untoward outcome. CONCLUSION: Conception shortly after a spontaneous miscarriage without waiting for at least the first postmiscarriage menstrual period is not associated with adverse maternal or neonatal outcomes compared with those of women with similar interpregnancy intervals who conceived after their next menstrual period.

Assessing the effectiveness of empiric antimicrobial regimens in cases of septic/infected abortions.

INTRODUCTION: Infected abortion is a life-threatening condition that requires immediate surgical and medical interventions. We aimed to assess the common pathogens associated with infected abortion and to test the microbial coverage of various empiric antimicrobial regimens based on the bacteriological susceptibility results in women with infected abortions. METHODS: A retrospective study in a single university-affiliated tertiary hospital. Electronic records were searched for clinical course, microbial characteristics, and antibiotic susceptibility of all patients diagnosed with an infected abortion. The effectiveness of five antibiotic regimens was analyzed according to bacteriological susceptibility results. RESULTS: Overall, 84 patients were included in the study. The mean age of patients was 32.3(SD ±â€¯5.8) years, and the median gestational age was 15 (IQR 8-19) weeks. Risk factors for infection were identified in 23 patients (27.3%), and included lack of medical insurance (n = 12), recent amniocentesis/chorionic villus sampling or fetal reduction due to multifetal pregnancies (n = 10). The most common pathogens isolated were Enterobacteriaceae (35%), Streptococci (31%), Staphylococci (9%) and Enterococci (9%). The combination of intravenous ampicillin, gentamicin and metronidazole showed significant superiority over all the other tested regimens according to the susceptibility test results. Piperacillin-tazobactam as an empiric single-agent drug of choice and provided a superior microbial coverage, with a coverage rate of 93.3%. CONCLUSIONS: A combination of ampicillin, gentamicin, and metronidazole had a better spectrum of coverage as a first-line empiric choice for patients with infected abortion.

Can We Prevent Stillbirth?

OBJECTIVE: This study aimed to identify the frequency of potentially preventable causes of stillbirth in a large heterogeneous population. STUDY DESIGN: This is a retrospective study of all stillbirth cases between January 2011 and December 2016 at a single tertiary medical center. Deliveries resulting from a nonviable fetus prior to 24 weeks of gestation, intrapartum fetal death, and incomplete stillbirth workup were excluded. Potentially preventable stillbirth was defined as that of a nonanomalous fetus that most likely resulted from one or more of the following: (1) placental-mediated complications, (2) postterm pregnancy, (3) monochorionicity-associated complications, (4) cholestasis of pregnancy, (5) preventable or treatable infections, and (6) isoimmunization. RESULTS: During the study period, 312 stillbirths were identified, 228 of which met the inclusion criteria. Of the 110 cases with a recognized cause, 47 (20.6%) were potentially preventable. The most common causes were placental-mediated complications and preventable or treatable infections, accounting for 75 and 9% of all potentially preventable causes, respectively. There were no recognizable maternal risk factors for potentially preventable stillbirth. CONCLUSION: One-fifth of all causes of stillbirth are potentially preventable. Due to the significant contribution of placental-mediated complications to preventable stillbirth, close sonographic surveillance and timely delivery may decrease risk substantially.