Comparison of live birth rates after IVF-embryo transfer with and without preimplantation genetic testing for aneuploidies.

RESEARCH QUESTION: Does the use of preimplantation genetic testing for aneuploidies (PGT-A) result in higher live birth rates when compared with both fresh and frozen embryo transfers (FET) not utilizing PGT-A? DESIGN: Retrospective cohort study at a single tertiary centre using inverse probability of treatment weighting (IPTW) to adjust for differences in baseline characteristics between groups. RESULTS: A total of 107 FET using PGT-A from 74 patients, along with 321 fresh and 286 FET not using PGT-A from 381 patients met the inclusion criteria for this study. In the IPTW-adjusted analysis of transfer-level data, PGT-A transfers resulted in a significantly higher live birth rate when compared with both non-PGT-A fresh (49.5% versus 38.6%, P = 0.036) and FET (50.6% versus 35.8%, P = 0.016). When data were analysed per retrieval level, the live birth rate was similar and acceptably high with or without PGT-A (63.7% versus 52.3%, P = 0.09). CONCLUSION: When comparing PGT-A to non-PGT-A fresh and FET, PGT-A embryo transfers have a significantly higher live birth rate. However, this difference did not persist at a per-retrieval level. Further investigation is needed to understand in what scenarios PGT-A has clinical significance and whether differences in the number of available embryos for transfer negates the benefit of PGT-A.

Is there still a role for a cleavage-stage embryo transfer?

OBJECTIVE: To determine whether pregnancy outcomes are poor or futile when an intended day 5 transfer is converted to a cleavage-stage transfer because of poor embryo development or a lower number of embryos. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Women with a limited number of embryos, defined as ≤6 two pronuclear embryos, after in vitro fertilization. INTERVENTIONS: Patients who had a cleavage-stage transfer were age matched with patients who had a day 5 transfer. MAIN OUTCOME MEASURES: Live birth rate. RESULTS: A total of 146 women were included in the study with 73 women in each group. Cleavage-stage transfer was associated with significantly lower implantation and clinical pregnancy rates compared with those of day 5 transfer. Although the live birth rate of the cleavage-stage transfer group was lower than that of the day 5 transfer group (25% vs. 40%, respectively), the cleavage-stage transfer still resulted in a live birth rate of 25%. A subanalysis comparing women who did and did not achieve live birth after cleavage-stage transfer demonstrated a live birth rate of 27% when at least one grade A embryo was transferred vs. 17% when a lesser quality embryo (grade B or C) was transferred. CONCLUSIONS: As expected, the live birth rate after cleavage-stage transfer was lower than that after day 5 transfer. However, the live birth rate of cleavage-stage transfer still fell into acceptable practice, >5%, for patients who were otherwise at very high risk of having no day 5 embryo transfer. Extended culture may not be necessary for all patients.

Testicular sperm extraction vs. ejaculated sperm use for nonazoospermic male factor infertility.

OBJECTIVE: To study the potential benefit of testicular sperm compared with ejaculated sperm for men with oligospermia. DESIGN: After exemption from institutional review board approval, we performed a retrospective cohort study using the Mayo Clinic Assisted Reproductive Technology database. SETTING: Single academic center. PATIENT(S): Couples with nonazoospermic male factor infertility (total motile sperm <25 million per ejaculate) undergoing intracytoplasmic sperm injection with sperm obtained by testicular sperm extraction (TESE) or ejaculated sperm between 2016 and 2019. INTERVENTION(S): In vitro fertilization, Intracytoplasmic sperm injection, TESE. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate. The secondary outcomes were fertilization rate, blastulation rate, pregnancy rate, and miscarriage rate. RESULT(S): Subjects in the two groups were similar in age, body mass index, and ovarian reserve. Baseline sperm parameters were similar in the two groups: total motile sperm (5.4 in the ejaculate sperm group vs. 3.6 million motile per ejaculate), except that baseline motility was higher in the group that used ejaculated sperm (40% vs. 29%). The total number of mature oocytes retrieved was similar in the two groups, but the use of TESE was associated with a 20% decrease in fertilization (60.0% vs. 80.6%) and half the number of blastocyst embryos (two vs. four) compared with ejaculated sperm. Compared with ejaculated sperm, use of TESE did not improve the miscarriage rate (11% vs. 9%) or the live birth rate (50.0% vs. 31.3%). CONCLUSION(S): Patients with male factor infertility and oligozoospermia did not have improved ICSI outcomes with the use of TESE samples compared with ejaculated sperm.

Myomectomy associated blood transfusion risk and morbidity after surgery.

OBJECTIVE: To evaluate blood transfusion risks and the associated 30-day postoperative morbidity after myomectomy. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Women who underwent myomectomies for symptomatic uterine fibroids (N = 3,407). INTERVENTION(S): Blood transfusion during or within 72 hours after myomectomy. MAIN OUTCOME MEASURE(S): The primary outcomes were rate of blood transfusion with myomectomy and risk factors associated with receiving a transfusion. The secondary outcome was 30-day morbidity after myomectomy. RESULT(S): The overall rate of blood transfusion was 10% (hysteroscopy, 6.7%; laparoscopy, 2.7%; open/abdominal procedures, 16.4%). Independent risk factors for transfusion included as follows: black race (adjusted odds ratio [aOR] 2.27, 95% confidence interval [CI] 1.62-3.17) and other race (aOR 1.77, 95% CI 1.20-2.63) compared with white race; preoperative hematocrit <30% compared to ≥30% (aOR 6.41, 95% CI 4.45-9.23); preoperative blood transfusion (aOR 2.81, 95% CI 1.46-5.40); high fibroid burden (aOR 1.91, 95% CI 1.45-2.51); prolonged surgical time (fourth quartile vs. first quartile aOR 11.55, 95% CI 7.05-18.93); and open/abdominal approach (open/abdominal vs. laparoscopic aOR 9.06, 95% CI 6.10-13.47). Even after adjusting for confounders, women who required blood transfusions had an approximately threefold increased risk for experiencing a major postoperative complication (aOR 2.69, 95% CI 1.58-4.57). CONCLUSION(S): Analysis of a large multicenter database suggests that the overall risk of blood transfusion with myomectomy is 10% and is associated with an increased 30-day postoperative morbidity. Preoperative screening of women at high risk for transfusion is prudent as perioperative transfusion itself leads to increased major postoperative complications.

Decreased gremlin 1 expression in women with BMI ≥35 kg/m2 is mediated by interleukin 10 and interleukin 1ß in the follicular fluid.

OBJECTIVE: To determine how body mass index (BMI) affects the follicular fluid cytokine milieu and investigate how this inflammatory environment impacts cumulus signaling. DESIGN: Experimental study. SETTING: Tertiary hospital based research laboratory. PATIENTS: Women with normal (18.5 to 24.9 kg/m2) and obese (35 to 42 kg/m2) BMI undergoing controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI). INTERVENTIONS: Cumulus cell treatment with obese follicular fluid, interleukin (IL) 10, and IL-1ß. MAIN OUTCOME MEASURES: Follicular fluid cytokine concentrations between normal and obese women were compared using multiplex bead assay. Differential cumulus cell gene expression of GREM1, HAS2, PTGS2, and VCAN were measured using quantitative reverse polymerase chain reaction (RT-qPCR) while protein levels were determined by flow cytometry and confocal microscopy. RESULTS: Compared to women with normal BMI, women with BMI ≥35 kg/m2 undergoing ICSI had higher follicular concentrations of IL-10 (9.46 pg/mL [0.59-19.16] vs 53.39 pg/mL [14.97-236.37], p=0.004) and IL-1ß (1.92 pg/mL [1.92-5.18] vs 5.18 pg/mL [1.92-16.33], p=0.017), as well as decreased relative cumulus cell expression of GREM1 (1.01 [0.66-1.40] vs 0.51 [0.38-0.74], p=0.03), a surrogate marker of positive ICSI outcomes. Furthermore, elevated IL-10 and IL-1ß appear to be responsible for decreasing GREM1 expression in women with BMI ≥35 kg/m2. CONCLUSION: Our findings suggest that follicular inflammation associated with obesity impacts cumulus cell signaling. At a molecular level, derangements to the immune system resulting in decreased GREM1 expression may be a partial explanation for the suboptimal ICSI outcomes observed with obesity.

Simulation in shoulder dystocia: does it change outcomes?

Background: Shoulder dystocia is an obstetrical emergency that requires immediate and appropriate provider response to decrease neonatal morbidity. Objective: To determine whether institution of shoulder dystocia simulation training improves maternal and neonatal outcomes at delivery. Study design: This retrospective cohort study compared maternal and neonatal outcomes before (1 September 2008-31 December 2009) and after (1 January 2010-31 December 2014) a mandatory shoulder dystocia simulation curriculum was instituted. Χ2 and Fisher's exact tests along with multivariate logistic regression models were conducted to adjust for potential confounding. Results: Of 8930 vaginal deliveries that met eligibility criteria over the 6-year period, 299 (3.3%) deliveries were complicated by a shoulder dystocia. The adjusted frequency of shoulder dystocia was approximately two times higher after training implementation (1.9% vs 3.8%; adjusted OR=1.80 (1.23 to 2.65), p=0.003). Neonatal outcomes such as brachial plexus injury (5.0% vs 7.7%; p=0.75), clavicle fracture (5.0% vs 4.6%; p=1.00) and humerus fracture (0.0% vs 1.9%; p=1.00) were not statistically different after training. Additionally, no significant differences in episiotomy (5.0% vs 4.6%; p=1.00), postpartum haemorrhage (10.0% vs 12.4%; p=0.80) and severe perineal laceration (10.0% vs 6.6%; p=0.50) were observed. Conclusions: The overall frequency of shoulder dystocia reportedly doubled after training despite stable operative vaginal delivery and caesarean delivery rates. No significant improvements were seen in maternal or neonatal outcomes after simulation training. As shoulder dystocias are rare events, simulation training may not necessarily improve neonatal outcomes, but it may increase overall provider awareness and intervention.

Neonatal Morbidity and Maternal Complication Rates in Women With a Delivery Body Mass Index of 60 or Higher.

OBJECTIVE: To investigate neonatal morbidity and maternal complication rates with delivery body mass index (BMI) 60 or greater. METHODS: This retrospective, multicenter cohort study included singleton pregnancies between 23 and 42 weeks of gestation from January 2005 to April 2016. Women with BMI 60 or greater were compared with a random sample of women with BMI 30-59. The primary outcome, composite neonatal morbidity, was defined as 5-minute Apgar score less than 7, hypoglycemia, respiratory distress syndrome, sepsis, hospital stay greater than 5 days, neonatal intensive care unit admission, or neonatal death. Secondary outcomes included maternal labor and delivery characteristics and complication rates. Kruskal-Wallis tests and χ or Fisher exact tests were used to compare BMI categories. Multivariable logistic regression was used for adjusted analysis. RESULTS: The study included 338 women, with 39 in the BMI 60 or greater group. An association between obesity and neonatal morbidity was found. Increasing BMI correlated with increasing neonatal morbidity, with the highest rates among those with BMI 60 or greater (BMI 30-39 [17%], 40-49 [19%], 50-59 [22%], 60 or greater [56%]; P<.001). After adjustment for confounders, obese women with BMI less than 60 had at least a 75% reduction in odds of neonatal morbidity compared with women with BMI 60 or greater (BMI 30-39 adjusted odds ratio [OR] 0.22 [0.1-0.5], 40-49 adjusted OR 0.23 [0.1-0.6], 50-59 adjusted OR 0.25 [0.1-0.6]). Maternal complication rates including labor induction, cesarean delivery, wound complication, postpartum hemorrhage, and hospital stay greater than 5 days were also significantly increased with BMI 60 or greater. CONCLUSION: A BMI 60 or greater at the time of delivery is significantly associated with increased neonatal morbidity and increased maternal complication rates. In addition, neonatal morbidity and maternal complication rates with BMI 60 or greater were significantly higher when compared with women in any lesser obese BMI cohort between 30 and 59.