Review of contributory factors in maternity admissions to intensive care at a New Zealand tertiary hospital.

OBJECTIVE: The purpose of this study was to identify factors that contributed to severe maternal morbidity, defined by admission of pregnant women and women in the postpartum period to the intensive care unit (ICU) from 2010-2011 at Auckland City Hospital (ACH), a tertiary hospital that delivers 7500 women/year, and to determine potentially avoidable morbidity with the use of local multidisciplinary review. STUDY DESIGN: All admissions of pregnant women and women in the postpartum period (to 6 weeks) to the ICU at ACH from 2010-2011 were identified from hospital databases. Case notes were summarized and discussed by a multidisciplinary team. The presence of contributory factors and potentially avoidable morbidity were determined by consensus with a tool that was developed by the New Zealand Perinatal and Maternal Mortality Review Committee for the review of maternal and perinatal deaths. Specific recommendations for clinical management were identified by the multidisciplinary group. RESULTS: Nine pregnant women and 33 women in the postpartum period were admitted to the ICU from 2010-2011. Contributory factors were identified in 30 cases (71%); 20 cases (48%) were considered to be potentially avoidable; personnel factors were the most commonly identified avoidable causes. Specific recommendations that resulted from the study included the need for the development of guidelines for puerperal sepsis, improved planning for women at known risk of postpartum hemorrhage, enhanced supervision of junior staff, and enhanced communication through multidisciplinary meetings. CONCLUSION: Forty-eight percent of severe maternal morbidity, which was defined as admission to the ICU at ACH from 2010-2011, was considered to be potentially avoidable by a local multidisciplinary review team; priorities were identified for improvement of local maternity services.

New research questions identified for Cochrane reviews: a cross-sectional study of a specialized register: part two: fertility.

OBJECTIVES: The aim of this project was to identify gaps and research waste in the dissemination of fertility evidence in Cochrane systematic reviews (CSRs). STUDY DESIGN AND SETTING: A cross-sectional study of The Cochrane Gynecology and Fertility (CGF) Group's specialized register of randomized controlled trials (RCTs). We included trials on fertility problems published in 2010 and 2011. These trials were matched, by the condition and treatment, to existing CSRs. Unmatched trials were analyzed to prioritize new review titles. RESULTS: We exported 564 trials from the CGF specialized register and found that 115 (23%) of these could be included in an existing CSR if these were updated while 72 trials (14%) were not matched to any review topic, and from these, eight new Cochrane review titles were developed. The topic with the largest number of associated 'unused' trials was 'Traditional Chinese medicine for women undergoing assisted reproductive techniques'. CONCLUSION: This project found that 14% of fertility trials were 'unused' and from these we identified new review topics and identified those reviews that need to be updated, thereby identifying the gaps in evidence for people with infertility.

New research questions identified for Cochrane reviews: a cross-sectional study of a specialized register: part one: gynecology.

OBJECTIVES: The aim of this project was to identify gaps and research waste in the dissemination of gynecology evidence in Cochrane systematic reviews (CSRs). STUDY DESIGN AND SETTING: A cross-sectional study of the Cochrane Gynecology and Fertility (CGF) Group's specialized register of randomized controlled trials (RCTs). We included trials on benign gynecological conditions, published in 2010 and 2011. These trials were matched, by the condition and treatment, to existing Cochrane reviews. Unmatched trials were analysed to prioritize new review titles. RESULTS: After exporting 740 trials from the CGF specialized register, we found that 192 (26%) could be included in an existing CSR if it was updated, whereas 230 trials (32%) were not matched to any review title, and from these, we developed 21 new review titles. The topic with the largest number of associated 'unused' trials was 'Plant and herbal extracts for symptoms of menopause'. CONCLUSIONS: We found that a third of the benign gynecology trials published in 2010 and 2011 had no associated CSR. After identifying new topics from unmatched trials, we developed new CSR titles. This study identified the gaps in the evidence for women with gynecological problems.

Pregnancy and birth outcomes of single versus multiple embryo transfer in gestational surrogacy arrangements: a systematic review and meta-analysis.

Multiple embryo transfer (MET) is associated with both an increased risk of multiple pregnancy and of live birth. In recent years, MET has become standard practice for most surrogacy arrangements. There is limited review of the use of MET versus single embryo transfer (SET) in surrogacy practice. The present review systematically evaluated the pregnancy outcomes of surrogacy arrangements between MET versus SET among gestational carriers. A systematic search of five computerized databases without restriction to the English language or study type was conducted to evaluate the primary outcomes: (i) clinical pregnancy; (ii) live delivery; and (iii) multiple delivery rates. The search returned 97 articles, five of which met the inclusion criteria. The results showed that clinical pregnancy (RR = 1.21, 95% CI: 1.06-1.39, n = 5, I2 = 41%), live delivery (RR = 1.29, 95% CI: 1.10-1.51, n = 4, I2 = 35%) and multiple delivery rates (RR = 1.42, 95% CI: 6.58-69.73, n = 4, I2 = 54%) were statistically significantly different in MET compared to SET. Adverse events including miscarriage, preterm birth and low birthweight were found following MET. Our findings support the existing evidence that MET results in multiple pregnancy and subsequently more adverse outcomes compared to SET. From a public health perspective, SET should be advocated as the preferred treatment for gestational carriers.

Outcome reporting across randomized controlled trials evaluating potential treatments for male infertility: a systematic review.

STUDY QUESTION: What are the primary outcomes and outcome measures used in randomized controlled trials (RCTs) evaluating potential treatments for male infertility in the last 10 years? SUMMARY ANSWER: Outcome reporting across male infertility trials is heterogeneous with numerous definitions and measures used to define similar outcomes. WHAT IS KNOWN ALREADY: No core outcome set for male infertility trials has been developed. Male infertility trials are unique in that they have potentially three participants, a man, a female partner and their offspring and this will likely lead to significant variation in outcome reporting in randomized trials. STUDY DESIGN SIZE DURATION: A systematic review of RCTs mapping outcomes and outcome measures evaluating potential treatments for men with infertility registered in the Cochrane Register of Controlled Trials (CENTRAL) between January 2010 and July 2021. PARTICIPANTS/MATERIALS SETTING METHODS: Abstract screening and study selection was undertaken in duplicate using a review protocol that was developed prior to commencing the review. No risk of bias assessment was undertaken as this review aims to report on outcome reporting only. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and seventy-five RCTs were identified, and given the large number of studies we limited our review to the 100 largest trials. Seventy-nine different treatments were reported across the 100 largest RCTs including vitamin and dietary supplements (18 trials), surgical treatments (18 trials) and sperm selection techniques (22 trials). When considering the largest 100 trials (range: 80-2772 participants), 36 primary and 89 secondary outcomes were reported. Forty-seven trials reported a primary outcome and 36 trials clearly defined their primary outcome. Pregnancy outcomes were inconsistently reported and included pregnancy rate (51 trials), pregnancy loss including miscarriage, ectopic pregnancy, stillbirth (9 trials) and live birth (13 trials). Trials consistently reporting the same outcome frequently used different definitions. For example, semen quality was reported by 75 trials and was defined in 7 different ways, including; the World Health Organization (WHO) 2010 criteria (32 trials), WHO 1999 criteria (18 trials), WHO 1992 criteria (3 trials), WHO 1999 and 1992 criteria (1 trial) and the Kruger strict morphology criteria (1 trial). LIMITATIONS REASONS FOR CAUTION: We only evaluated the 100 largest trials published in the last 10 years and did not report outcomes on the remaining 75. An outcome was included as a primary outcome only if clearly stated in the manuscript and we did not contact authors to clarify this. As our review mapped outcomes and outcome measures, we did not undertake an integrity assessment of the trials included in our review. WIDER IMPLICATIONS OF THE FINDINGS: Most randomized trials evaluating treatments for male infertility report different outcomes. Only half of the RCTs reported pregnancy rate and even fewer reported live birth; furthermore, the definitions of these outcomes varies across trials. Developing, disseminating and implementing a minimum data set, known as a core outcome set, for male infertility research could help to improve outcome selection, collection and reporting. STUDY FUNDING/COMPETING INTERESTS: A.P.-chairman of external scientific advisory committee of Cryos International Denmark ApS, member of the scientific advisory board for Cytoswim LDT and ExSeed Health. Guest lecture at the 'Insights for Fertility Conference', funded by MERK SERONO Limited. M.v.W.-holds a ZON-MW research grant. No external funding was obtained for this study.

Expression and regulation of DNA methyltransferases in human endometrium.

The messenger RNA of the DNA methyltransferases DNMT3a and DNMT3b are expressed temporally in the endometrium across the menstrual cycle, as is the steroid hormone regulation of DNMT1, DNMT3a, and DNMT3b. This suggests that DNA methylation in endometrium is changeable during the menstrual cycle and potentially alters gene expression.

Measuring outcomes in fertility trials: can we rely on clinical pregnancy rates?

OBJECTIVE: To assess whether the estimates of treatment effect in randomized clinical trials (RCTs) in reproductive medicine differ when either clinical pregnancy or live birth is used as the outcome measure. DESIGN: Metaanalysis. SETTING: We analyzed RCTs in reproductive medicine found in systematic reviews published in the Cochrane Library that reported on both clinical pregnancy and live birth. PATIENT(S): Subfertile couples. INTERVENTION(S): For each individual RCT, data on clinical pregnancy and live birth were extracted. MAIN OUTCOME MEASURE(S): We compared the outcome of each study by calculating a kappa-statistic (statistically significant treatment effective or not) and by comparing the odds ratio by calculating the ratio of the odds ratios (ROR). RESULT(S): We found 67 systematic reviews, of which 42 reported on pregnancy and live birth. These 42 reviews included 654 RCTs, of which 143 (22%) reported both on pregnancy and live birth. The pregnancy loss rates in the treatment and control groups were comparable. Of the 143 RCTs, the conclusion based on pregnancy rate and live birth rate was comparable (kappa value of 0.81; 95% confidence interval [CI], 0.68-0.94). The odds ratios estimating treatment effect from pregnancy and live birth were also comparable (ROR, 1.01, 95% CI 0.9 to 1.12). CONCLUSION(S): Only a minority of randomized clinical trials in reproductive medicine report on live birth. Conclusions on the effectiveness of a treatment based on either clinical pregnancy or live birth as endpoints are comparable.

Ectopic pregnancy: an update.

PURPOSE OF REVIEW: This review discusses recent publications that investigate the epidemiology, diagnosis and treatment of ectopic pregnancy. RECENT FINDINGS: Transvaginal ultrasound is being used with increasing confidence for the diagnosis of ectopic pregnancy, and methotrexate now has an established role in the treatment of ectopic pregnancy. No serum markers have been found that can reliably differentiate intrauterine from extrauterine pregnancy. As more experience has been gained with medical therapy, it is apparent that it is possible to identify a subgroup of women in whom it is unlikely to succeed. The use of adjunctive therapy such as mifepristone does not appear to increase the effectiveness of methotrexate. Screening for ectopic pregnancy in at-risk women has been suggested, but it may be of only limited value. In the surgical management of ectopic pregnancy the effect on fertility of salpingotomy and salpingectomy remains uncertain, although recent cohort studies suggest that salpingotomy may be associated with a better subsequent intrauterine pregnancy rate than salpingectomy. A number of case reports of pregnancies at unusual sites continue to be published, but in the last 2 years there has been a dramatic increase in the number of caesarean scar pregnancies reported. SUMMARY: Medical therapy now has an established role in the treatment of ectopic pregnancy, but it is clear that careful patient selection is essential. In the surgical management of ectopic pregnancy the effects of salpingotomy and salpingectomy on subsequent fertility are uncertain and need further investigation.