The effect of ovarian follicle size on oocyte and embryology outcomes.

OBJECTIVE: To identify relationships between the size of punctured ovarian follicles and subsequent embryology outcomes. DESIGN: Prospective observational cohort study. SETTING: Private fertility center. PATIENTS: One hundred fifty-seven oocyte retrievals performed during the study period. INTERVENTIONS: The diameter of punctured follicles was ultrasonically measured during routine oocyte collection. The resulting embryos were group-cultured to the blastocyst stage and classified into 8 groups according to follicle size (≤9.5, 10-12.5, 13-15.5, 16-18.5, 19-21.5, 22-24.5, 25-27.5, and ≥28 mm). MAIN OUTCOME MEASURE: Rate of good-quality blastocysts per follicle puncture. RESULTS: This study included 4,539 follicle punctures, 2,348 oocytes, 1,772 mature oocytes, 1,258 bipronuclear (2pn) oocytes, and 571 good-quality blastocysts derived from 157 oocyte retrievals. The per-puncture yields of oocytes, mature oocytes, 2pn oocytes, and good-quality blastocysts were associated with the size of the punctured follicle. The rates of good-quality blastocysts per punctured follicle were 2.2% (≤9.5 mm), 6.2% (10-12.5 mm), 11.9% (13-15.5 mm), 14.5% (16-18.5 mm), 18.9% (19-21.5 mm), 17.5% (22-24.5 mm), 15.9% (25-27.5 mm), and 16.0% (≥28 mm). When compared with the overall average, punctures of follicles in groups ≤12.5 mm in diameter had significantly inferior yields of good-quality blastocysts, whereas punctures of follicles in groups 19-24.5 mm in diameter were associated with significantly greater than average yields of good-quality blastocysts. Other groups did not differ significantly from average. No correlation was observed between follicle diameter and ploidy of biopsied blastocysts. CONCLUSIONS: Punctures of follicles ≤12.5 mm in diameter rarely result in good-quality blastocysts. The yield of good-quality blastocysts progressively increases with follicle size up to approximately 19 mm in diameter, with no substantial decline above that size. The ploidy of the blastocysts that form appears to be unaffected by follicle size.

The change in endometrial thickness following progesterone exposure correlates with in vitro fertilization outcome after transfer of vitrified-warmed blastocysts.

PURPOSE: To determine if the change in endometrial thickness following exogenous progesterone (P) initiation correlates with outcome following autologous transfer of a single thawed blastocyst. METHODS: The study is a retrospective observational cohort study conducted at a private fertility center. Patients scheduled for thawed blastocyst transfer received artificial endometrial preparation (artificial cycle FET) and underwent serial ultrasonography. The main outcomes were the rate of ongoing pregnancy (fetal heart motion at 12 weeks of gestation) and early pregnancy loss. Logistic regression was used to test for correlations between these outcomes and the change in endometrial thickness while adjusting for potential confounders (patient age, embryo quality, and the use of genetic testing). RESULTS: There were 232 qualifying autologous single-blastocyst transfers in the 20-month study period ending 31 December 2019. Mean endometrial thicknesses were 3.8 mm, 10.0 mm, and 11.2 mm at baseline, P initiation, and at transfer, respectively. The change in endometrial thickness after exogenous P exposure ranged from - 5 to + 9 mm and negatively correlated with ongoing pregnancy in logistic regression analyses. Specifically, ongoing pregnancy rates per transfer were 63.2% in 19 cases where endometria compacted by 10% or more, 64.2% in 95 cases where there was unchanged endometrial thickness, and 52.5% in 118 cases where endometria expanded. CONCLUSIONS: The change in endometrial thickness after P initiation was associated with the probability of ongoing pregnancy but not with early pregnancy loss. Ongoing pregnancy rates were greater in endometria with negative growth (compaction) when compared to endometria that grew (expanded) after P exposure.

Comparison of birth weights in patients randomly assigned to fresh or frozen-thawed embryo transfer.

OBJECTIVE: To estimate birth weight differences between patients randomized to fresh or thawed ET. DESIGN: Post hoc analysis of results from two similar randomized trials. SETTING: Private fertility center. PATIENT(S): One hundred thirty-four first-time IVF patients, ages 18-40 years at oocyte retrieval, who had live birth. INTERVENTION(S): Patients were randomly assigned to have either fresh blastocyst transfer or all bipronuclear oocytes frozen followed by thaw, extended culture, and blastocyst transfer in a subsequent cycle. Preimplantation genetic screening was not allowed. MAIN OUTCOME MEASURE(S): Mean birth weight. RESULT(S): After allowing for the contributions of multiple significant variables (gestational age at birth, the presence of a vanished twin, number of infants delivered) in multiple linear regression, the adjusted mean birth weight was 166 g (95% confidence interval, 43-290 g) lower after fresh blastocyst transfer when compared with transfer of blastocysts derived from thawed bipronuclear oocytes. CONCLUSION(S): Birth weights are lower in cycles with fresh blastocyst transfer after controlled ovarian stimulation than in transfers of frozen-thawed embryos in the absence of ovarian stimulation. This finding confirms similar results reported in many retrospective studies. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00963625 and NCT00963079.

Low Anti-Müllerian Hormone in Pediatric Cancer Survivors in the Early Years after Gonadotoxic Therapy.

STUDY OBJECTIVE: To obtain anti-Müllerian hormone (AMH) levels in female childhood cancer survivors and determine the association of therapeutic exposures with diminished ovarian reserve (DOR). DESIGN: Cross-sectional study. SETTING: Academic medical center. PARTICIPANTS: Forty-nine survivors (mean age = 14.9 years, SD = 3.3 years; mean time without therapy = 7.5 years, SD = 3.6 years) who received alkylator/heavy metal chemotherapy, and/or radiation exposure to the ovaries with 2 or more years without therapy were recruited. INTERVENTIONS: None. MAIN OUTCOME MEASURES: AMH, follicle stimulating hormone (FSH) levels (random), and therapeutic characteristics such as cyclophosphamide equivalent dose (CED), heavy metal exposure, and bilateral ovarian radiation exposure were determined for each subject. DOR was defined as a low AMH (less than the fifth percentile for age-matched controls), and premature ovarian insufficiency as an FSH greater than 40 IU/L with AMH less than the fifth percentile. RESULTS: Fourteen subjects (28.6%) had DOR, and 5 (10.2%) had premature ovarian insufficiency. Those with a low AMH were more likely exposed to a higher CED (P = .001) and/or bilateral ovarian radiation exposure (P = .048). In the multivariate model of DOR adjusted for age at diagnosis, DOR was associated with bilateral radiation (odds ratio = 39.9; 95% confidence interval 2.1-759.7; P = .04). There was a nonsignificant trend with increasing odds of low AMH with increased CED. CONCLUSION: DOR, defined by an AMH less than the fifth percentile, was observed in more than one-quarter of pediatric cancer survivors exposed to gonadotoxic cancer therapy and was significantly associated with bilateral ovarian irradiation. Identifying risk factors for low AMH prompts AMH and FSH surveillance in the early years after cancer therapy and, if needed, early referral to a reproductive specialist.

Assessment of Long-Term Bowel Symptoms After Segmental Resection of Deeply Infiltrating Endometriosis: A Matched Cohort Study.

STUDY OBJECTIVE: To assess long-term bowel symptoms in women who underwent segmental bowel resection for deep-infiltrating endometriosis (DIE) compared with women who underwent resection of severe endometriosis without bowel resection. DESIGN: Cohort study with matched controls (Canadian Task Force classification II-2). SETTING: Cleveland Clinic. PATIENTS: 71 patients (36 cases and 35 controls). INTERVENTIONS: Patients who were at least 4 years out from undergoing segmental bowel resection due to DIE were matched with patients who had undergone resection of stage III/IV endometriosis without bowel resection. The patients completed validated questionnaires, and data were analyzed using the Wilcoxon rank-sum, χ(2), and Fisher exact tests. MEASUREMENTS AND MAIN RESULTS: The Bristol Stool Form Scale, Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM), and St Mark's Vaizey Fecal Incontinence Grading System were used to elicit information. The median duration of follow-up was 10.1 years (range, 4-18 years). The mean patient age and body mass index were comparable in the cases and the controls. A larger proportion of cases than controls reported new bowel symptoms (58% [21 of 36] vs 14% [5 of 35]; p = .001), as well as abdominal pain, incomplete bowel movements, and false alarms on the PAC-SYM questionnaire; however, total PAC-SYM and Vaizey Fecal Incontinence Grading System scores were similar in the 2 groups (median, 8 [interquartile range, 8-10] vs 8 [8-10]; p = .86). Similarly, the proportion of patients with normal stool consistency (Bristol Stool Form Scale score 2-6) was similar in the 2 groups (80.6% [29 of 36] vs 94.3% [33 of 35]; p = .59). CONCLUSION: Segmental bowel resection for DIE may be associated with a higher incidence of new bowel symptoms (possibly due to abdominal pain, incomplete bowel movements, and/or false alarms), but not with worse constipation or fecal incontinence, compared with surgery without bowel resection.

Preterm birth and its long-term effects: methylation to mechanisms.

The epigenetic patterns established during development may influence gene expression over a lifetime and increase susceptibility to chronic disease. Being born preterm (<37 weeks of gestation) is associated with increased risk mortality and morbidity from birth until adulthood. This brief review explores the potential role of DNA methylation in preterm birth (PTB) and its possible long-term consequences and provides an overview of the physiological processes central to PTB and recent DNA methylation studies of PTB.

Comparison of robotic and laparoscopic myomectomy.

OBJECTIVE: To compare surgical outcomes of patients with symptomatic leiomyomas after robot-assisted ("robotic") or laparoscopic myomectomy. STUDY DESIGN: Retrospective chart review of 81 patients undergoing robotic (n=40) or laparoscopic (n=41) myomectomy. Data included fibroid characteristics (number, weight, location, and pathologic findings), operating time, blood loss, complications, and postoperative hospitalization length. RESULTS: Patients undergoing laparoscopy had a significantly larger mean uterine size, larger mean size of the largest fibroid, and greater number of fibroids. When adjusted for uterine size and fibroid size and number, no significant differences were noted between robotic vs laparoscopic groups for mean operating time (141 vs 166 minutes), mean blood loss (100 vs 250 mL), intraoperative or postoperative complications (2% vs 20% and 11% vs 17%, respectively), hospital stay more than 2 days (12% vs 23%), readmissions, or symptom resolution. CONCLUSION: Short-term surgical outcomes were similar after robotic and laparoscopic myomectomy; long-term outcomes were not assessed.

Pivotal Advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response.

Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors, indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with T helper cell type 2-dependent immune responses and that recruitment is a dynamic, ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial-restricted. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.