Cleavage Patterns of 9600 Embryos: The Importance of Irregular Cleavage.

This prospective, observational study investigated the incidence of irregular cleavage (IRC) among human embryos and its influence on IVF treatment outcomes. It included 1001 women who underwent 1976 assisted reproduction treatments during 2016-2021 in a single IVF clinic. Embryo morphokinetics were analyzed and evaluated for the association between IRC and women's characteristics, treatment characteristics, and pregnancy outcomes. The incidence of IRC was 17.5% (1689/9632 embryos). Of these, 85% of the embryos had one IRC, 15% had multiple IRC and 35% of IRC events occurred during the embryo's first cell cycle. IRC embryos were found to correlate with male factor (p = 0.01) and higher ICSI rate (p = 0.01). Age, BMI, parity, basal FSH level, stimulation protocol, and number of retrieved oocytes did not differ between groups. Embryos with early IRC or more than one IRC had lower blastulation rates (p = 0.01 for each). Fresh cycles with IRC embryos had a lower clinical pregnancy rate (p = 0.01) and embryos with early IRC had a lower live birth rate (p = 0.04) compared to embryos without IRC. Frozen transfer cycles of blastocyst embryos, with or without IRC, had comparable results. In conclusion, the number of abnormal cleavage events and their timing are important factors in the prognosis of the developing human embryo.

High initial ß-hCG predicts IVF outcomes accurately and precludes the need for repeated measurements.

This study evaluated ß-human chorionic gonadotropin (hCG) changes during the early period of pregnancy in an attempt to predict successful pregnancy outcomes in ART. It determined the median values of the ß-hCG and the 2-day ß-hCG increments of clinical vs biochemical pregnancies. The results of fresh day 3 embryo, frozen day 3 embryo, and frozen day 5 embryo transfers were evaluated. The cutoff values of ß-hCG and the 2-day increments predicting clinical pregnancy and delivery were determined. All women who underwent embryo transfer and had a singleton pregnancy from January 2017 to December 2019 were included. As expected, clinical pregnancies had higher initial median ß-hCG values compared to biochemical pregnancies (fresh day 3 (400 vs 73 mIU/mL), frozen day 3 (600 vs 268.5 mIU/mL) and frozen day 5 (937 vs 317 mIU/mL)). Nonetheless, the abortion rate was significantly lower in the group with ß-hCG above the cutoff values in fresh (141 mIU/mL) and frozen (354.5 mIU/mL) cleavage stage transfers (17.2% vs 44%, P < 0.001 and 18.5% vs 38%, P = 0.003, respectively). Blastocyst transfers resulted in higher median initial ß-hCG compared to cleavage embryo transfers (937 vs 600 mIU/mL), and the initial ß-hCG values from frozen cleavage embryos were higher compared to fresh cleavage embryos (600 vs 400 mIU/mL). Earlier implantation in frozen cycles may be caused by freezing-thawing procedures. Moreover, in fresh cycles, negative effects of the hormonal milieu of fresh cycles may delay implantation. These results indicate that high initial ß-hCG and high 2-day ß-hCG increments demonstrated better outcomes, including more clinical pregnancies and fewer abortions.

Ovulatory-cycle frozen embryo transfer: spontaneous or triggered ovulation and the impact of LH elevation at hCG triggering.

The effect of the luteinizing hormone (LH) elevation before the human chorionic gonadotropin (hCG) trigger in ovulatory frozen-thawed embryo transfer (Ovu-FET) cycles has not been determined. We aimed to investigate whether triggering ovulation in Ovu-FET cycles affects the live birth rate (LBR), and the contribution of elevated LH at the time of hCG trigger. This retrospective study included Ovu-FET cycles performed in our center from August 2016 to April 2021. Modified Ovu-FET (hCG trigger) and true Ovu-FET (without hCG trigger) were compared. The modified group was divided according to whether hCG was administered, before or after LH increased to > 15 IU/L and was twice the baseline value. The modified (n = 100) and true (n = 246) Ovu-FET groups and both subgroups of the modified Ovu-FET, those who were triggered before (n = 67) or after (n = 33) LH elevation, had comparable characteristics at baseline. Comparison of true vs. modified Ovu-FET outcomes revealed similar LBR (35.4% vs. 32.0%; P = 0.62), respectively. LBR were similar between the modified Ovu-FET subgroups regardless of the hCG trigger timing (31.3% before vs. 33.3% after LH elevation; P = 0.84). In conclusion, LBR of Ovu-FET were not affected by hCG trigger or whether LH was elevated at the time of hCG trigger. These results add reassurance regarding hCG triggering even after LH elevation.

Is There an Added Neonatal Risk in Vacuum-Assisted Deliveries with Nuchal Cord?

This retrospective cohort study assessed the association between nuchal cord and adverse outcomes during vacuum-assisted delivery (VAD). Women with singleton pregnancies, 34−41-weeks gestation, who underwent VAD, from 2014 to 2020 were included. The primary outcome was umbilical cord pH ≤ 7.1. Secondary outcomes were neonatal intensive care unit admission, Apgar scores, pH < 7.15, subgaleal hematoma, shoulder dystocia and third/fourth-degree perineal tear. Outcomes were compared between neonates with (1059/3754, 28.2%) or without (71.8%) nuchal cord after VAD. No difference in cord pH ≤ 7.1 was found between groups. The nuchal cord group had a lower rate of nulliparity (729 (68.8%) vs. 2004 (74.4%), p = 0.001) and higher maternal BMI (23.6 ± 4.3 vs. 23.1 ± 5, p = 0.017). Nuchal cord was associated with higher rates of induction (207 (19.5%) vs. 431 (16%), p = 0.009) and lower birthweights (3185 ± 413 vs. 3223 ± 436 g, p = 0.013). The main indication for VAD in 830 (80.7%) of the nuchal cord group was non-reassuring fetal heart rate (NRFHR) vs. 1989 (75.6%) controls (p = 0.004). The second stage was shorter in the nuchal cord group (128 ± 81 vs. 141 ± 80 min, p < 0.001). Multivariate regression found nulliparity, induction and birthweight as independent risk factors for nuchal cord VAD. Although induction and NRFHR rates were higher in VAD with nuchal cord, the rate of umbilical cord acidemia was not.

Can 17 hydroxyprogesterone caproate (17P) decrease preterm deliveries in patients with a history of PMC or pPROM?

BACKGROUND: A history of spontaneous preterm birth (sPTB) is a significant risk factor for recurrence. Intra-muscular-7α-hydroxyprogesterone caproate (17P) has been the preventive treatment of choice until the recent "Prolong study" that reported no benefit. OBJECTIVE: To determine the benefit of (17P) treatment in preventing reoccurrence of sPTB, by evaluating two presenting symptoms of the first sPTB: premature contractions (PMC) and preterm premature rupture of membranes (pPROM). STUDY DESIGN: This retrospective study included 342 women with a previous singleton sPTB followed by a subsequent pregnancy. sPTB were either due to PMC (n = 145) or pPROM (n = 197). During the subsequent pregnancy, 90 (26.3%) patients received 250 mg 17P IM. Each presenting symptom-PMC or pPROM-was evaluated within itself comparing treated vs. untreated groups. Data were analyzed using t-test, Chi-square and Fisher's exact test. Logistic regression analysis was also performed. RESULTS: Patients treated with 17P in the subsequent pregnancy had delivered earlier in the previous pregnancy (33.4w vs. 35.3w in the PMC group, and 34.1w vs. 35.7w in the pPROM group, p<0.001). In the following pregnancy, they had higher admission rates due to suspected preterm labor (31.7% vs. 10.9% in the treated vs. untreated PMC group (p = 0.003) and 26.1% vs. 5.4% in the treated vs. untreated pPROM group (p<0.001). In both groups, but more prominently in the previous PMC group, treatment compared to non-treatment in the subsequent pregnancy significantly prolonged it (4.3w vs. 2.6w in the PMC group (p = 0.007), and 3.7w vs. 2.7w in the pPROM group (p = 0.018)). The presenting symptom of sPTB in the following pregnancy tended to recur in cases of another sPTB, with a significantly greater likelihood of repeating the sPTB mechanism in cases with PMC, regardless of receiving 17P (69% in the PMC cohort and 60% in the pPROM cohort, p<0.001). CONCLUSIONS: 17P might delay preterm delivery in patients with a previous sPTB on an individual level (prolongation of the pregnancy for each patient compared to her previous delivery). Therefore, our results imply that 17P can decrease potential premature delivery complications for patients with a previous sPTB due to PMC or pPROM.

Fetal weight estimation in tall women: is ultrasound more accurate than clinical assessment? A prospective trial.

PURPOSE: Estimated fetal weight (EFW) is crucial for clinical decision-making during pregnancy and labor. Maternal habitus impacts its accuracy. This study compared the accuracy of clinical versus ultrasound EFW in tall pregnant women (height ≥ 172 cm, 90th percentile). METHODS: In this prospective study, tall pregnant women at term, who arrived for a prenatal visit and delivered within a week, underwent clinical and ultrasound assessments of estimated fetal weight. Each woman served as her own control. After delivery, birth weight was compared to the clinical and ultrasound EFW. The primary outcome was the accuracy of each method in predicting the actual birth weight. RESULTS: All 100 women included in this trial underwent clinical and ultrasound estimations of fetal weight. Mean maternal height was 175.7 ± 3.3 (172-185) cm. More clinical EFW swere inaccurate compared to ultrasound (25 (25%) vs. 6 (6%), respectively, p < 0.001). Both clinical (3583 g) and ultrasound (3490 g) evaluations underestimated the fetal weights compared to the birth weights (3664 g, p < 0.001). In the macrosomic fetal group, both the clinical (3983 g) and ultrasound (3767 g) estimates were significantly inaccurate compared to the birth weights (4237 g, p < 0.001). CONCLUSION: Among tall women, ultrasound EFW is more accurate than clinical EFW. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: IRB-0016-17-MMC, Clinical-Trials.gov identifier NCT03206281.

Twin pregnancies and perinatal outcomes: a comparison between fresh and frozen embryo transfer: a two-centre study.

RESEARCH QUESTION: To assess the perinatal and obstetric outcomes of twin pregnancies resulting from IVF frozen embryo transfer (FET) in comparison with fresh embryo transfer. DESIGN: A retrospective cohort study of 773 twin pregnancies conceived via IVF treatment. Data were collected from the records of two outpatient fertility IVF clinics of cycles conducted between 2006 and 2016. RESULTS: A total of 773 pregnancies were evaluated: 614 (79.4%) following FET and 159 (20.6%) following fresh embryo transfer. The FET group had a significantly higher mean birthweight (P = 0.002), and lower rates of small for gestational age (P = 0.003), low (P = 0.003) and very low birthweight (P = 0.006) infants. Also, a significantly lower rate of spontaneous second trimester miscarriage compared with the fresh embryo transfer group was observed (P = 0.001). No significant difference was found between groups regarding gestational age at delivery, term birth (after 37 weeks of gestation), twin discordancy rate, fetal major malformation rate, and hospitalization duration. CONCLUSION: In twin pregnancies, FET might have better perinatal outcomes compared with fresh embryo transfer in regards to birthweight and spontaneous second trimester miscarriages. Further research is needed to evaluate these results.

Unheard voices: complaint patterns of older persons in the health care system.

To examine the patterns and prevalence of complaints about health services among older clients of Health Maintenance Organizations (HMOs), explore demographic correlates, and compare results with the patterns in the younger population. Primary data were collected from the responses of subjects who participated in two national phone surveys, conducted in Israel over a period of 2 years. The final sample included 372 participants aged 65 and older, and 796 younger persons, who believed they had reasons to complain about their HMO. Of the 372 participants with cause to complain, only 23% had actually complained. Subjects who were 75-years-old and above, with below-average income, had 2.5 times higher probability for not complaining than people under 65. No statistically significant differences were found between the older participants and younger participants regarding the reasons for complaints or the procedures for making them. Recommendations are made for the recognition of older persons as a unique group within the health care system and for developing organizational mechanisms for capturing their unheard voices by HMOs.

Systematic comparison of four sources of drug information regarding adjustment of dose for renal function.

OBJECTIVE: To compare advice on dosage adjustment for renal impairment provided by four commonly used secondary pharmacotherapeutic sources. DESIGN: Systematic comparison of the definitions of renal impairment, recommendations for dosage adjustment, and the evidence in support of these recommendations in four information sources. DATA SOURCES: British National Formulary, Martindale: the Complete Drug Reference, American Hospital Formulary System Drug Information, and Drug Prescribing in Renal Failure. REVIEW METHODS: Two reviewers independently extracted data on recommendations for dosage adjustment for impaired renal function of 100 drugs often used in our hospital. RESULTS: The four sources differed in their recommendations for adjustments of dosage and dosing interval. They vary in their definitions of renal impairment; some are qualitative and remain unclear. All sources provide only a general description; the methods on which the advice is based and references for original data are rarely presented. CONCLUSIONS: The remarkable variation in definitions and recommendations, along with scarce details of the methods used to reach this advice, makes the available sources of drug information ill suited for clinical use. The methods used to retrieve information and use data should be described and made available to the reader. Advice on drug prescription, dose and dosing interval, contraindications, and adverse effects should be evidence based.