Utilization of Cryopreserved Oocytes in Patients With Poor Ovarian Response After Planned Oocyte Cryopreservation.

Importance: Poor ovarian response (POR) to stimulation may impact patients' desire or need to utilize cryopreserved oocytes for family building in the future. These findings, captured by Society for Assisted Reproductive Technology (SART) national data, underscore the need for tailored counseling and further research into the decision-making processes influencing oocyte utilization. Objective: To examine the association of ovarian response to stimulation and the number of vitrified oocytes with the likelihood and timing of patients returning for oocyte utilization following planned oocyte cryopreservation (OC). Design, Setting, and Participants: This cohort study used data in the SART Clinical Outcome Reporting System for patients in US fertility clinics and data was used for eligible patients who underwent planned OC from January 2014 through December 2020. Data were analyzed from November 2022 to June 2023. Main outcomes and measures: The association between number of oocytes cryopreserved on return rate to utilize cryopreserved oocytes and the time from vitrification to warming. Results: A total of 67 893 autologous oocyte freezing cycles were performed in the US between 2014 and 2020, among 47 363 patients (mean [SD] age, 34.5 [4.7] years). Of these, 6421 (13.5%) were classified as patients with POR, with fewer than 5 oocytes vitrified across all ovarian stimulation cycles. A total of 1203 patients (2.5%) returned for oocyte warming and utilization. The rate of return was significantly higher in the POR group, with 260 (4.0%) returning compared with 943 (2.3%) in the normal responder group (P < .001). This trend was most notable in the age 30 to 34 years (warm cycle, 46 of 275 [16.7%] vs no warm cycle, 982 of 11 743 [8.4%]; P < .001) and age 35 to 39 years groups (warm cycle, 124 of 587 [21.1%] vs no warm cycle, 3433 of 23 012 [14.9%]; P < .001). The time elapsed from vitrification to warming was comparable between patients with POR (mean [SD], 716.1 [156.1] days) and normal responders (803.8 [160.7] days). A multivariate analysis adjusted for age, clinic region in the US, body mass index, and history of endometriosis was conducted to identify factors associated with the utilization of oocytes. The analysis revealed that having fewer than 5 oocytes vitrified was associated with higher odds of utilizing oocytes (OR, 1.52; 95% CI, 1.32-1.76). Conclusions and Relevance: This cohort study reveals a distinct pattern in the utilization of cryopreserved oocytes among patients undergoing planned OC in the US. Despite the increase in number of patients pursuing OC, there is a notably low rate of return to utilize previously vitrified oocytes; notably, patients with POR are more likely to return, although the time to return is similar to those with normal ovarian response.

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.

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.

Estimating predictors of severity of group A Streptococcus infection in pregnancy.

OBJECTIVE: To identify the clinical characteristics of pregnancy associated group A streptococcus (GAS) infection and predictors for intensive care unit (ICU) admission. METHODS: A retrospective cohort study of culture-proven pregnancy-related GAS infections in tertiary hospital Electronic medical records were reviewed, for cases of cultures positive GAS that were identified between January 2008 and July 2021. A GAS infection was defined by the isolation of the pathogen from a sterile liquid or tissue site. Blood and urine cultures were obtained from all patients with peripartum hyperpyrexia (fever >38 °C). Medical Personnel screening included cultures of the throat, rectum, and skin lesions (if present). In cases of hemodynamic instability patients were transferred ad hoc to ICU, according to the obstetrician and intensivist judgment. RESULTS: Of the 143,750 who delivered during the study period, 66 (0.04%) were diagnosed as having a pregnancy associated GAS infection. Of these, 57 patients presented postpartum, and represented the study cohort. The most common presenting signs and symptoms among puerperal GAS, were postpartum pyrexia (72%), abdominal pain (33%), and tachycardia (>100 bpm, 22%). 12 women (21.0%) developed streptococcal toxic shock syndrome (STSS. Predictors for STSS and ICU admission were: antibiotic administration >24 h from presentation postpartum, tachycardia, and a C-reactive protein level >200 mg/L. Women that received antibiotic prophylaxis during labor had a significantly lower rate of STSS (0 vs 10, 22.7%; p = .04). CONCLUSION: Deferral of medical intervention >24 h from the first registered abnormal sign had the most important impact on deterioration of women with invasive puerperal GAS. Antibiotic prophylaxis during labor in women with GAS may reduce associated complications.

Fertility Preservation in Endometriosis: Does Patient Symptomatology Affect the Extent of the Ovarian Response?

This study is to identify factors and patient symptomatology affecting ovarian response in women with endometriosis who seek fertility preservation. An observational cross-sectional study was conducted from July 2017 to May 2020 at a tertiary university-affiliated medical center. We included patients who were treated in the endometriosis clinic and underwent fertility preservation. Patients completed an online questionnaire that was cross-referenced with electronic charts. An analysis related to patient data and fertility preservation cycles and a mediation analysis were performed. The mean patient age at time of fertility preservation was 35.2 (± 4.9) years. The mean accumulated number of oocytes vitrified per patient was 16.7 (± 12.1) oocytes. The correlation coefficient assessed between the number of oocytes vitrified per cycle and AMH was significantly positive at +0.472, p = 0.006. The examined reported symptoms were lethargy, chronic pelvic pain, dyschezia, dyspareunia, bowel-associated symptoms, and urinary tract symptoms. The number of oocytes vitrified correlated with the number of reported symptoms and clinical characteristics at - 0.497, p = 0.0001, and - 0.442, p = 0.0001, respectively. In a mediation analysis, the potential causality of surgical intervention in the relationship between the number of symptoms and ovarian response was - 0.300 (95% CI [0.15, 1.905], p = 0.05), and the calculated proportion of mediation was estimated to be 17%. We observed a significant negative association between the number of clinical symptoms and the quantity of vitrified oocytes. This relationship was only partly associated with prior surgical intervention. AMH was found to have the highest correlation with treatment success in patients with endometriosis undergoing fertility preservation.

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.

Labor induction in third trimester non-viable fetus.

OBJECTIVE: We aimed to assess the efficacy of three different labor induction methods for non-viable third-trimester fetuses. METHODS: This retrospective cohort study included women who had an intra-uterine fetal death or termination of pregnancy at or after 28 weeks of gestation and underwent labor induction by either transcervical foley catheter and concomitant oxytocin infusion or regular doses of vaginal Prostin© or Propess©.The primary outcome was induction to the delivery interval. Secondary outcomes included the rate of women who delivered within 24 h, time spent in the delivery room, failed induction, adverse outcomes and reported occurrence of moderate to severe pain. RESULTS: Between January 2017 to June 2020, 107 women met the inclusion criteria. 25 women underwent induction of labor using transcervical foley catheter, 44 using Propess©, and 58 by Prostin©. The three groups were found to be demographically similar. The rate of women who delivered within 24 h was higher in the transcervical foley catheter group compared to the Propess© and Prostin© groups (72% vs 25% vs 29.3%, p < .001 respectively). Time to delivery was shorter among the transcervical foley catheter group compared to the Propess© and Prostin© groups (16.97 h vs 39.4 vs 39.3, p < .001 respectively). When comparing the Foley catheter group to both Propess© and Prostin©, moderate to severe pain was significantly more commonly reported in the prostaglandins groups (36.0% vs 50.0% vs 65.62%, p = .04). No difference was found in adverse outcomes, defined as intrapartum fever, post-partum hemorrhage and retained placenta. CONCLUSION: Cervical foley catheter with concomitant oxytocin infusion is the most effective method for induction of labor in third trimester non-viable in fetus compared to PGE2.

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.

A diagnosis of diminished ovarian reserve does not impact embryo aneuploidy or live birth rates compared to patients with normal ovarian reserve.

OBJECTIVE: To estimate the aneuploidy rates in young women with diminished ovarian reserve (DOR) before treatment and poor ovarian response (POR) postretrieval. DESIGN: Retrospective cohort study. SETTING: A single academically-affiliated fertility clinic. PATIENT(S): Autologous frozen embryo transfer cycles from December 2014 to June 2020 were reviewed. Demographic and clinical factors that impact outcomes were used for propensity score matching (PSM) in a ratio of 2:1 and 4:1 for preimplantation genetic testing for aneuploidy pre-cycle DOR and POR after stimulation, respectively. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Aneuploid rates, defined as the number of aneuploid blastocysts divided by the number of biopsied blastocysts per cycle. No euploid embryos to transfer, defined as all cohorts of embryos being aneuploid. RESULT(S): A total of 383 women diagnosed with DOR were compared with matched controls. Aneuploid rates did not differ significantly between the two groups (42.2% vs. 41.7%; RR = 1.06; 95% CI, 0.95-1.06). No differences were identified in live birth rates per transfer between women with and without DOR after euploid single-embryo transfers (56.0% and 60.5%, respectively). An additional PSM analysis to assess aneuploidy rates for patients with POR (<5 oocytes) vs. those without it, resulted in similar rates of aneuploidy between the two comparison groups (41.1% vs. 44%, R = 1.02; 95% CI, 0.91-1.14). The prevalence of cycles with "no euploid embryos" in the POR cohort was higher (26% vs. 13%); however, rates of cases with a single embryo available for biopsy were lower in the DOR group, relative to controls (11% vs. 31%). CONCLUSION(S): Young women diagnosed with DOR or POR exhibited equivalent aneuploidy rates and live birth rates per euploid embryo transfer in a large matched population, based on age, body mass index, and IVF cycle initiation. The lower percentage of cycles with no euploid embryo available for transfer in DOR and POR patients is because of the decreased total number of oocytes/developing embryos and not because of increased aneuploidy rates in these groups.

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.

Twinning in ART: Single embryo transfer policy.

It is more than thirty years that perinatologists and healthcare personnel aim to reduce the morbidity associated with multiple pregnancy. In many cases, these complications stem from pregnancies achieved through artificial reproductive technologies (ART). Although dramatic measures have been taken to control those risks by increasing the proportion of single embryo transfers, the multiple pregnancy rate still remains relatively high among patient conceived through ART, carrying risks to both mothers and newborns, and is coupled with the related economic burden associated with prematurity. The aim of this review is to provide the current evidence regarding single embryo transfer to assist decision-makers and to promote patient knowledge toward an elective policy to reduce the risk of twinning. Single embryo transfer may aid in the further reduction of multiple pregnancy and, in most cases, will maintain patient autonomy and right of choice.

Ruptured ectopic pregnancies following methotrexate treatment: clinical course and predictors for improving patient counseling.

To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1-25). ß-hCG percentage change in the 48 h preceding MTX treatment and ß-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04-1.12, p < 0.001 for every percent change in ß-hCG; OR = 1.001, 95% CI = 1.0003-1.002 for every unit change in ß-hCG, respectively). In a decision tree analysis model, in women with ß-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to ß-hCG dynamics and level. The absolute risk for tubal rupture in women with ß-hCG increment<20% is low.

Calculating the appropriate prophylactic dose of cefazolin in women undergoing cesarean delivery.

BACKGROUND AND OBJECTIVES: Surgical site infection and other postoperative complications are relatively common in obstetrical procedures, and they are associated with morbidity, prolonged hospital stay, and readmissions. Appropriate levels of antimicrobial agents given directly before skin incision can prevent the establishment of surgical-related infection caused by endogenous microorganisms present on the woman's skin. We aimed to determine serum concentrations of cefazolin given to pregnant women prior to scheduled cesarean delivery and to compare their drug concentrations and pharmacokinetics in 2 weight groups. STUDY DESIGN: We conducted a prospective cohort analysis of the pharmacokinetics of cefazolin in women undergoing cesarean delivery (August 2017 to September 2018). One or two grams of intravenous cefazolin was administered within 30 min prior to skin incision to women weighing <80 kg and ≥80 kg, respectively. Maternal serum samples were obtained at skin incision and 30 min later. The serum concentration of cefazolin was measured by high-pressure liquid chromatography. Antimicrobial coverage was defined as being appropriate when the cefazolin levels were above the minimal inhibitory concentration. Pharmacokinetic parameters were estimated using a one-compartment model. RESULTS: A total of 61 women were enrolled, of whom 47 underwent cesarean delivery (study group). The mean time that had elapsed between drug administration to incision was 13 ± 6.9 min (95% confidence interval 10.6-16.2 min). The drug levels after 30 min in women who weighed >80 kg and in women who received 2 g cefazolin, after 30 min from incision differed significantly (87.0 ± 26.0 vs 55.4 ± 16.6 µg/ml, p = .0001). CONCLUSION: A single 1- or 2-g dose of cefazolin provides serum concentrations above minimal inhibitory concentrations for susceptible pathogens in most women undergoing scheduled cesarean delivery.

Low glucose at 3-hour 100 gram oral glucose tolerance test: implications for glucose control.

OBJECTIVE: To assess the clinical significance of a low 180-minute glucose value in a 100 g oral glucose tolerance test (OGTT) and a single high abnormal value. METHODS: A retrospective cohort study. The study group included women with 180-minute plasma glucose levels of ≤60 mg/dL and one abnormal value in the OGTT. The control group was comprised of women with one abnormal value in the OGTT and normal 180-minute glucose value. The primary outcome was glycemic control, defined as fasting blood glucose measurements > 90 mg/dL or post-prandial glucose values >140 mg/dL or 120 mg/dL (one-hour and two-hour post-prandial, respectively) in >30% of the measurements. Secondary outcomes were the rate of insulin treatment and the perinatal outcome consisting of birthweight, large-for-gestational-age, and polyhydramnios. RESULTS: Three hundred and one women were included, 143 in the study group and 158 in the control group. Pre-pregnancy BMI, first trimester fasting glucose levels, previous GDM, and familial diabetes were similar for both groups. Suboptimal glycemic control was more prevalent among the women in the study group (14% vs. 5.1%, respectively, p= .01). The need for insulin treatment was similar in both groups. CONCLUSIONS: Women with one abnormal value and a 180-minute hypoglycemia in the OGTT are at increased risk for suboptimal glycemic control.

Fetal Neuroprotective Mechanism of Maternal Magnesium Sulfate: Proteomic Analysis.

Mg supplementation has been shown to protect preterm fetuses from white and gray matter damage, but the mechanism is unclear. The purpose of this study was to study the effect of maternal inflammation on the overall protein panel of the fetal rat brain, as well as the neuroprotective effect of magnesium-sulfate (MG). Pregnant rats at e20 (n = 6, 18 total) received injections of i.p. lipopolysaccharide (LPS) 500 ug/kg or control saline (SAL) at time 0. Dams were randomized to treatment with s.c. MG (270 mg/kg loading followed by 27 mg/kg q20 min) or saline (SAL) from -2 to +2 h, followed by an additional injection of MG (270 mg/kg) at +2 h. At 4 h after LPS administration, fetal brains were collected from the 3 treatment groups (LPS/SAL, LPS/MG, SAL/SAL) and analyzed by proteomic technique. LPS significantly decreased fetal brain complement C3, alpha-1-antiproteinase, metallothionein-3, alpha-2-macroglobulin, neurosecretory protein VGF, glutathione S-transferase mu 2, fam91a1, cnot7, mitogen-activated protein kinase levels, and significantly increased fetal brain Hbg1, while MG treatment normalized these measures to normal values. Maternal inflammation may cause brain injury via pathways other than the activation of neurotoxic cytokines; this effect could be due to increased/decreased production of certain proteins associated with securing oligodendrocytes, encouraging neuronal growth in the brain, or protecting against cerebral ischemia. MG's neuroprotective activity may be achieved by modifying the effect of LPS on proteins involved in early brain development.

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.

A virtual reality system for pain and anxiety management during outpatient hysteroscopy-A randomized control trial.

BACKGROUND: Visual and acoustic virtual reality (VR) has been increasingly explored as a non-pharmacological tool for pain relief in clinical settings. OBJECTIVE: We aimed to evaluate the effectiveness of VR as a distraction technique in the management of acute pain during operative hysteroscopy in the outpatient setting. METHODS: A prospective, open-label, randomized control trial in a tertiary university-affiliated medical centre between April and August 2020. Overall, 82 women were randomly allocated to undergo operative hysteroscopy either with the use of VR (n = 44, study group) or with standard treatment (control group, n = 38). VR was applied throughout the procedure and no anaesthesia was given. The primary outcome measures included self-reported intraoperative pain. Other objectives included vital parameters as pulse rate (PR) and respiratory rate (RR) before and during the first 3 min of the procedure. Pain and anxiety outcomes were measured as numeric rating scores. RESULTS: The baseline parameters were similar between groups. The mean duration for the procedure was 8.1 ± 3.2 vs. 7.3 ± 6.0 min for the study and the control groups (p = 0.23). There were no statistically significant differences between the reported pain scores during the procedure [median (interquartile range) 5.0 (3.0-7.2) vs. 5.0 (3.0-8.0), respectively; p = 0.67]. While neither intraoperative heart rate nor respiratory rate differed between groups [14.0 (13.0-16.0) vs. 14.0 (11.0-16.5); p = 0.77)], the increase of heart rate was found greater in the VR group [+7.0 (8.5) vs. +1.0 (12.2); p = 0.01]. CONCLUSION: VR was not effective in reducing pain during an outpatient operative hysteroscopy. SIGNIFICANCE: The use of a Virtual reality system was found ineffective in reducing pain during and after an office operative hysteroscopy without anaesthesia, in a thorough examination of both continuous physiological parameters and women's self-reported measures.

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.