Clinical implementation of algorithm-based embryo selection is associated with improved pregnancy outcomes in single vitrified warmed euploid embryo transfers.

PURPOSE: To assess whether utilization of a mathematical ranking algorithm for assistance with embryo selection improves clinical outcomes compared with traditional embryo selection via morphologic grading in single vitrified warmed euploid embryo transfers (euploid SETs). METHODS: A retrospective cohort study in a single, academic center from September 2016 to February 2020 was performed. A total of 4320 euploid SETs met inclusion criteria and were included in the study. Controls included all euploid SETs in which embryo selection was performed by a senior embryologist based on modified Gardner grading (traditional approach). Cases included euploid SETs in which embryo selection was performed using an automated algorithm-based approach (algorithm-based approach). Our primary outcome was implantation rate. Secondary outcomes included ongoing pregnancy/live birth rate and clinical loss rate. RESULTS: The implantation rate and ongoing pregnancy/live birth rate were significantly higher when using the algorithm-based approach compared with the traditional approach (65.3% vs 57.8%, p<0.0001 and 54.7% vs 48.1%, p=0.0001, respectively). After adjusting for potential confounding variables, utilization of the algorithm remained significantly associated with improved odds of implantation (aOR 1.51, 95% CI 1.04, 2.18, p=0.03) ongoing pregnancy/live birth (aOR 1.99, 95% CI 1.38, 2.86, p=0.0002), and decreased odds of clinical loss (aOR 0.42, 95% CI 0.21, 0.84, p=0.01). CONCLUSIONS: Clinical implementation of an automated mathematical algorithm for embryo ranking and selection is significantly associated with improved implantation and ongoing pregnancy/live birth as compared with traditional embryo selection in euploid SETs.

The correlation between morphology and implantation of euploid human blastocysts.

RESEARCH QUESTION: Does the composite morphology score or a particular developmental component (expansion stage, inner cell mass [ICM] or trophectoderm [TE]) of euploid blastocysts undergoing single frozen embryo transfer (FET) impact ongoing pregnancy/live birth (OP/LB) rates? DESIGN: Retrospective cohort study including a total of 2236 embryos from 1629 patients who underwent single euploid FET between 2012 and 2017. RESULTS: Embryos with an ICM grade of A compared with C had a higher OP/LB rate (55.6% versus 32.3%, P < 0.001). Blastocysts with a TE grade of A or B compared with C had a higher likelihood of OP/LB (A versus C: odds ratio [OR] 1.6, 99% confidence interval [CI] 1.1-2.3, B versus C: OR 1.5, 99% CI 1.1-2.1), and blastocysts with a developmental stage of 4 or 5 compared with 6 had higher odds of OP/LB (4 versus 6: OR 1.6, 99% CI 1.2-2.2, 5 versus 6: OR 1.6, 99% CI 1.2-2.3). CONCLUSIONS: Among euploid embryos, ICM morphology is the best predictor of sustained implantation; however, a composite score may provide additional guidance. While there is a known benefit in genomic screening prior to embryo selection, morphology provides individualized, prognostic information about implantation potential.

Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening.

Pre-implantation genetic diagnosis (PGD) has changed the landscape of clinical genetics by helping families reduce the transmission of monogenic disorders. However, given the high prevalence of embryonic aneuploidy, particularly in patients of advanced reproductive age, unaffected embryos remain at high risk of implantation failure or pregnancy loss due to aneuploidy. 24-chromosome aneuploidy screening has become widely utilized in routine in vitro fertilization (IVF) to pre-select embryos with greater pregnancy potential, but concurrent 24-chromosome aneuploidy screening has not become standard practice in embryos biopsied for PGD. We performed a retrospective cohort study of patients who underwent PGD with or without 24-chromosome aneuploidy screening to explore the value of concurrent screening. Among the PGD + aneuploidy-screened group (n = 355 blastocysts), only 25.6 % of embryos were both Single Gene Disorder (SGD)-negative (or carriers) and euploid; thus the majority of embryos were ineligible for transfer due to the high prevalence of aneuploidy. Despite a young mean age (32.4 ± 5.9y), 49.9 % of Blastocysts were aneuploid. The majority of patients (53.2 %) had ≥1 blastocyst that was Single Gene Disorder (SGD)-unaffected but aneuploid; without screening, these unaffected but aneuploid embryos would likely have been transferred resulting in implantation failure, pregnancy loss, or a pregnancy affected by chromosomal aneuploidy. Despite the transfer of nearly half the number of embryos in the aneuploidy-screened group (1.1 ± 0.3 vs. 1.9 ± 0.6, p < 0.0001), the implantation rate was higher (75 % vs. 53.3 %) and miscarriage rate lower (20 % vs. 40 %) (although not statistically significant). 24-chromosome aneuploidy screening when performed concurrently with PGD provides valuable information for embryo selection, and notably improves single embryo transfer rates.

Osteoporosis risk factors and early life-style modifications to decrease disease burden in women.

Prevention of osteoporosis should begin in childhood and continue throughout adulthood. Although genetic determinants of muscle and bone mass may offer other therapeutic options in the future, currently, counseling should primarily focus on lifestyle modification including healthy dietary practices and regular exercise. Vitamin supplementation, particularly vitamin D, should be considered to enhance diet based on patient's need. Attention to estrogen status is also important. In addition, patients should be counseled regularly about cigarette cessation and avoiding moderate alcohol intake.

Evaluating in vitro fertilization outcomes of patients with low body mass index following frozen-thawed embryo transfer.

OBJECTIVE: To determine the relationship between patients with a low body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) and in vitro fertilization (IVF) outcomes following frozen-thawed embryo transfer (FET). METHODS: Retrospective cohort study including 12 618 women aged 20-46 years with an underweight (<18.5) or normal weight (18.5-24.9) BMI who underwent controlled ovarian stimulation for IVF in a private and academic IVF center between August 2002 and December 2019. RESULTS: Anti-Müllerian hormone, peak estradiol levels, number of MII oocytes, and fertilized oocytes were greater in the underweight group compared with the normal weight group. The total required gonadotropin dose was lower in the underweight patients compared with the normal weight patients. MII, fertilization, blastulation, and euploid rates did not differ before and after adjusting for confounders between BMI groups. In a cohort of 316 patients who underwent preimplantation genetic testing for aneuploidy and single euploid FET, pregnancy loss, pregnancy, clinical pregnancy, and live birth rates before and after controlling for covariates were similar between groups. CONCLUSION: Although there are known fetal growth or obstetrical issues associated in patients with a low BMI, it is reassuring that these risks do not extend to embryologic or clinical outcomes from IVF treatment.

Understanding the Reproductive Experience and Pregnancy Outcomes of Lesbian Women Undergoing Donor Intrauterine Insemination.

PURPOSE: The study purpose was to evaluate the reproductive experience, specifically cycle characteristics and treatment outcomes, of lesbian women. In addition, we aimed to determine whether there are differences in pregnancy outcomes when comparing lesbian women undergoing ovulation induction (OI) versus natural cycles with donor intrauterine insemination (IUI), as well as lesbian and heterosexual women undergoing the same assisted reproductive technology treatment. METHODS: This was a retrospective cohort study including women who underwent an IUI with cryopreserved sperm between 2006 and 2018. The primary outcome of interest was clinical pregnancy (CP) rate. RESULTS: A total of 216 lesbian women (451 natural cycles and 441 OI cycles) and 584 heterosexual women (1177 natural cycles and 1238 OI cycles) were included in the study. Thirty percent of lesbian women had a hysterosalpingogram as part of their initial workup. Approximately 40% of lesbian women who underwent OI/IUI had previously undergone at least one natural cycle/IUI. There was no significant difference in CP rate when comparing lesbian women and heterosexual women undergoing natural or OI/IUI, or when comparing lesbian women who underwent natural versus OI/IUI cycles. However, there was a significantly higher multiple gestation rate among lesbian women undergoing OI compared with those undergoing natural cycles (11.8% vs. 0%, p = 0.01). CONCLUSION: This large study showed that while pregnancy outcomes were similar between groups, the multiple gestation rate was higher in lesbian women undergoing OI compared with lesbian women undergoing natural cycles.

Embryo aneuploidy is not impacted by selective serotonin reuptake inhibitor exposure.

OBJECTIVE: To study whether maternal exposure to selective serotonin reuptake inhibitors (SSRIs) has any influence on rates of blastocyst aneuploidy and/or in vitro fertilization (IVF) cycle outcomes. DESIGN: Retrospective cohort analysis. SETTING: Private and academic IVF center. PATIENT(S): Patients who underwent IVF with preimplantation genetic treatment with trophectoderm biopsy (n = 4,355 cycles) and patients who underwent a single-embryo transfer (SET) between January-2012 and June-2017 (n = 2,132 cycles). INTERVENTION(S): Comprehensive chromosome screening and euploid SET. MAIN OUTCOME MEASURE(S): Odds of embryo aneuploidy. RESULT(S): Of 19,464 embryos analyzed, 3.9% (n = 743) were exposed to a SSRI, and the remaining 96.1% (n = 18,721) were not. The embryo euploid rate was 52.1%, and the aneuploid rate was 42.5%; 5.4% of the reports were inconclusive. No differences were found in clinical and IVF characteristics among the cohorts. After controlling for cofounders, there was no statistically significant associations between exposure to SSRIs and the odds of aneuploidy (adjusted odds ratio [OR] 0.04; 95% confidence interval [CI], -0.04-0.09). In a subanalysis including 2,132 thawed SET cycles, no differences were observed in implantation rate (71.3% vs. 70.1%; OR 0.60; 95% CI, 0.60-1.47), clinical pregnancy rate (58.2% vs. 59.7%; OR 0.70; 95% CI, 0.70-1.61), loss rate (18.5% vs. 11.49%; OR 1.54; 95% CI, 0.94-2.54), or multiple pregnancy rate (0.6% vs. 0; OR 0.7; 95% CI, 0.02-7.32) between cohorts. CONCLUSION(S): Patients exposed to SSRIs in vivo are not susceptible to an increased rate of embryo aneuploidy in IVF. The IVF outcomes of patients exposed to SSRIs do not differ from those of unexposed patients.

The female athlete triad.

CONTEXT: The female athlete triad (the triad) is an interrelationship of menstrual dysfunction, low energy availability (with or without an eating disorder), and decreased bone mineral density; it is relatively common among young women participating in sports. Diagnosis and treatment of this potentially serious condition is complicated and often requires an interdisciplinary team. EVIDENCE ACQUISITION: Articles from 1981 to present found on PubMed were selected for review of major components of the female athlete triad as well as strategies for diagnosis and treatment of the conditions. RESULTS: The main goal in treatment of young female athletes with the triad is a natural return of menses as well as enhancement of bone mineral density. While no specific drug intervention has been shown to consistently improve bone mineral density in this patient population, maximizing energy availability and optimizing vitamin D and calcium intake are recommended. CONCLUSIONS: Treatment requires a multidisciplinary approach involving health care professionals as well as coaches and family members. Prevention of this condition is important to minimize complications of the female athlete triad.

Bone microarchitecture is impaired in adolescent amenorrheic athletes compared with eumenorrheic athletes and nonathletic controls.

CONTEXT: Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. OBJECTIVE: We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. DESIGN AND SETTING: We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. SUBJECTS AND OUTCOME MEASURES: We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15-21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. RESULTS: Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18-24% of the variability in tibial trabecular number and separation. CONCLUSION: In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA.