Home-based monitoring of ovulation to time frozen embryo transfers in the Netherlands (Antarctica-2): an open-label, nationwide, randomised, non-inferiority trial.

BACKGROUND: The growing field of assisted reproductive techniques, including frozen-thawed embryo transfer (FET), should lead the way to the best sustainable health care without compromising pregnancy chances. Correct timing of FET is crucial to allow implantation of the thawed embryo. Nowadays, timing based on hospital-controlled monitoring of ovulation in the natural cycle of a woman is the preferred strategy because of the assumption of favourable fertility prospects. However, home-based monitoring is a simple method to prevent patient travel and any associated environmental concerns. We compared ongoing pregnancy rates after home-based monitoring versus hospital-controlled monitoring with ovulation triggering. METHODS: This open-label, multicentre, randomised, non-inferiority trial was undertaken in 23 hospitals and clinics in the Netherlands. Women aged between 18 and 44 years with a regular ovulatory menstrual cycle were randomly assigned in a 1:1 ratio via a web-based randomisation program to home-based monitoring or hospital-controlled monitoring. Those who analysed the data were masked to the groups; those collecting the data were not. All endpoints were analysed by intention to treat and per protocol. Non-inferiority was established when the lower limit of the 90% CI exceeded -4%. This study was registered at the Dutch Trial Register (Trial NL6414). FINDINGS: 1464 women were randomly assigned between April 10, 2018, and April 13, 2022, with 732 allocated to home-based monitoring and 732 to hospital-controlled monitoring. Ongoing pregnancy occurred in 152 (20·8%) of 732 in the home-based monitoring group and in 153 (20·9%) of 732 in the hospital-controlled monitoring group (risk ratio [RR] 0·99 [90% CI 0·81 to 1·22]; risk difference [RD] -0·14 [90% CI -3·63 to 3·36]). The per-protocol analysis confirmed non-inferiority (152 [21·0%] of 725 vs 153 [21·0%] of 727; RR 1·00 (90% CI 0·81 to 1·23); RD -0·08 [90% CI -3·60 to 3·44]). INTERPRETATION: Home-based monitoring of ovulation is non-inferior to hospital-controlled monitoring of ovulation to time FET. FUNDING: The Dutch Organisation for Health Research and Development.

Increased obstetric and neonatal risks in artificial cycles for frozen embryo transfers?

RESEARCH QUESTION: What are the obstetric and neonatal risks for women conceiving via frozen-thawed embryo transfer (FET) during a modified natural cycle compared with an artificial cycle method. DESIGN: A follow-up study to the ANTARCTICA randomized controlled trial (RCT) (NTR 1586) conducted in the Netherlands, which showed that modified natural cycle FET (NC-FET) was non-inferior to artificial cycle FET (AC-FET) in terms of live birth rates. The current study collected data on obstetric and neonatal outcomes of 98 women who had a singleton live birth. The main outcome was birthweight; additional outcomes included hypertensive disorder of pregnancy, premature birth, gestational diabetes, obstetric haemorrhage and neonatal outcomes including Apgar scores and admission to the neonatal ward or the neonatal intensive care unit and congenital anomalies. RESULTS: Data from 82 out of 98 women were analysed according to the per protocol principle. There was no significant difference in the birthweights of children born between groups (mean difference -124 g [-363 g to 114 g]; P = 0.30). Women who conceived by modified NC-FET have a decreased risk of hypertensive disorders of pregnancy compared with AC-FET (relative risk 0.27; 95% CI 0.08-0.94; P = 0.031). Other outcomes, such as rates of premature birth, gestational diabetes or obstetric haemorrhage and neonatal outcomes, were not significantly different. CONCLUSIONS: The interpretation is that modified NC-FET is the preferred treatment in women with ovulatory cycles undergoing FET when the increased risk of obstetrical complications and potential neonatal complications in AC-FET are considered.

Fresh versus frozen embryo transfers in assisted reproduction.

BACKGROUND: In vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments conventionally consist of a fresh embryo transfer, possibly followed by one or more cryopreserved embryo transfers in subsequent cycles. An alternative option is to freeze all suitable embryos and transfer cryopreserved embryos in subsequent cycles only, which is known as the 'freeze all' strategy. This is the first update of the Cochrane Review on this comparison. OBJECTIVES: To evaluate the effectiveness and safety of the freeze all strategy compared to the conventional IVF/ICSI strategy in women undergoing assisted reproductive technology. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two registers of ongoing trials from inception until 23 September 2020 for relevant studies, checked references of publications found, and contacted study authors to obtain additional data. SELECTION CRITERIA: Two review authors (TZ and MZ) independently selected studies for inclusion, assessed risk of bias, and extracted study data. We included randomised controlled trials comparing a 'freeze all' strategy with a conventional IVF/ICSI strategy including a fresh embryo transfer in women undergoing IVF or ICSI treatment. DATA COLLECTION AND ANALYSIS: The primary outcomes were cumulative live birth rate and ovarian hyperstimulation syndrome (OHSS). Secondary outcomes included effectiveness outcomes (including ongoing pregnancy rate and clinical pregnancy rate), time to pregnancy and obstetric, perinatal and neonatal outcomes. MAIN RESULTS: We included 15 studies in the systematic review and eight studies with a total of 4712 women in the meta-analysis. The overall evidence was of moderate to low quality. We graded all the outcomes and downgraded due to serious risk of bias, serious imprecision and serious unexplained heterogeneity. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study during the interim analysis, unit of analysis error, and absence of adequate study termination rules. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below. There is probably little or no difference in cumulative live birth rate between the 'freeze all' strategy and the conventional IVF/ICSI strategy (odds ratio (OR) 1.08, 95% CI 0.95 to 1.22; I2 = 0%; 8 RCTs, 4712 women; moderate-quality evidence). This suggests that for a cumulative live birth rate of 58% following the conventional strategy, the cumulative live birth rate following the 'freeze all' strategy would be between 57% and 63%. Women might develop less OHSS after the 'freeze all' strategy compared to the conventional IVF/ICSI strategy (OR 0.26, 95% CI 0.17 to 0.39; I2 = 0%; 6 RCTs, 4478 women; low-quality evidence). These data suggest that for an OHSS rate of 3% following the conventional strategy, the rate following the 'freeze all' strategy would be 1%. There is probably little or no difference between the two strategies in the cumulative ongoing pregnancy rate (OR 0.95, 95% CI 0.75 to 1.19; I2 = 31%; 4 RCTs, 1245 women; moderate-quality evidence).  We could not analyse time to pregnancy; by design, time to pregnancy is shorter in the conventional strategy than in the 'freeze all' strategy when the cumulative live birth rate is comparable, as embryo transfer is delayed in a 'freeze all' strategy. We are uncertain whether the two strategies differ in cumulative miscarriage rate because the evidence is very low quality (Peto OR 1.06, 95% CI 0.72 to 1.55; I2 = 55%; 2 RCTs, 986 women; very low-quality evidence) and cumulative multiple-pregnancy rate (Peto OR 0.88, 95% CI 0.61 to 1.25; I2 = 63%; 2 RCTs, 986 women; very low-quality evidence). The risk of hypertensive disorders of pregnancy (Peto OR 2.15, 95% CI 1.42 to 3.25; I2 = 29%; 3 RCTs, 3940 women; low-quality evidence), having a large-for-gestational-age baby (Peto OR 1.96, 95% CI 1.51 to 2.55; I2 = 0%; 3 RCTs, 3940 women; low-quality evidence) and a higher birth weight of the children born (mean difference (MD) 127 g, 95% CI 77.1 to 177.8; I2 = 0%; 5 RCTs, 1607 singletons; moderate-quality evidence) may be increased following the 'freeze all' strategy. We are uncertain whether the two strategies differ in the risk of having a small-for-gestational-age baby because the evidence is low quality (Peto OR 0.82, 95% CI 0.65 to 1.05; I2 = 64%; 3 RCTs, 3940 women; low-quality evidence). AUTHORS' CONCLUSIONS: We found moderate-quality evidence showing that one strategy is probably not superior to the other in terms of cumulative live birth rate and ongoing pregnancy rate. The risk of OHSS may be decreased in the 'freeze all' strategy. Based on the results of the included studies, we could not analyse time to pregnancy. It is likely to be shorter using a conventional IVF/ICSI strategy with fresh embryo transfer in the case of similar cumulative live birth rate, as embryo transfer is delayed in a 'freeze all' strategy. The risk of maternal hypertensive disorders of pregnancy, of having a large-for-gestational-age baby and a higher birth weight of the children born may be increased following the 'freeze all' strategy. We are uncertain if 'freeze all' strategy reduces the risk of miscarriage, multiple pregnancy rate or having a small-for-gestational-age baby compared to conventional IVF/ICSI.

Severe postpartum hemorrhage increases risk of posttraumatic stress disorder: a prospective cohort study.

PURPOSE: To evaluate whether severe postpartum hemorrhage (PPH) is a risk factor for posttraumatic stress disorder (PTSD). Severe PPH can be experienced as a traumatic event. PTSD leads to negative mental health effects. Knowing risk factors for PTSD during childbirth offers opportunities for early interventions, which may prevent the development of PTSD. MATERIALS AND METHODS: In this prospective study, we compared two groups of participants; women with ≥2000 mL of blood loss (severe PPH, patients) and women with ≤500 mL of blood loss (controls). Participants were screened for PTSD using the PCL-5 four to six weeks after delivery. Positive screening was followed by the CAPS-5 to diagnose PTSD. RESULTS: We included 187 PPH patients and 121 controls. Median PCL-5 scores were higher for PPH patients (5.0) than controls (4.0, p = 0.005). Thirteen PPH patients (7.0%) and two controls (1.7%) scored ≥32 on the PCL-5, indicative of probable PTSD (OR 4.45, 95% CI 0.99-20.06, p = 0.035). Significant more PPH patients than controls met criteria for a clinical diagnosis of PTSD on the CAPS-5 (n = 10, 5.6% vs n = 0, 0.0%; p = 0.007). CONCLUSIONS: There is a significant and clinically relevant increased risk for developing PTSD after severe PPH. Gynecologists and midwives are advised to screen for PTSD at postpartum follow-up visits to prevent long-term negative mental health effects. CLINICAL TRIAL REGISTRATION: NL50273.100.14.

Posttraumatic stress disorder in partners following severe postpartum haemorrhage: A prospective cohort study.

BACKGROUND: Partners of women are increasingly present during childbirth and may be exposed to a traumatic experience. Since parents' mental health issues (i.e. posttraumatic stress disorder) have been shown to increase the risk of problems in the child's development, it is important to identify these risk factors. Partners often describe severe postpartum haemorrhage as traumatic. AIM: Whether witnessing severe postpartum haemorrhage is a risk factor for developing posttraumatic stress disorder in partners. METHODS: In this prospective cohort study, we compared partners of women with severe postpartum haemorrhage (≥2000 mL) and partners of women with ≤500 mL of blood loss (controls). Four weeks after birth partners were screened for posttraumatic stress disorder symptoms with a self-report questionnaire. Scores ≥11 were followed by a gold standard clinical interview to diagnose posttraumatic stress disorder. FINDINGS: We included 123 severe postpartum haemorrhage partners and 62 control partners. Partners of women with severe postpartum haemorrhage reported higher scores than control partners (median 3.0 (0.0-7.0) vs 2.0 (0.0-4.0), p = 0.04) on symptoms of posttraumatic stress, but no significant difference in probable posttraumatic stress disorder diagnosis according to the self-report questionnaire was found. According to the clinical interview no partners were diagnosed with posttraumatic stress disorder. Severe postpartum haemorrhage was experienced as traumatic by the partners who felt excluded. CONCLUSION: None of the partners developed posttraumatic stress disorder, revealing the resilience of young fathers. Because some partners reported severe postpartum haemorrhage as traumatic, we recommend sufficient information and support is provided during childbirth.

Quadruple torsion of the fallopian tube in an 18-year-old virgin: a rare twist.

In this report, we describe an 18-year-old nulliparous virgo, with no medical history, who presented herself at the emergency department with symptoms of lower abdominal pain and nausea with vomiting. On examination, an echogenic unilocular cyst with possible relation to the right ovary was found. The working diagnosis was an ovarian torsion. She underwent a diagnostic laparoscopy which revealed a quadruple torsion of the fallopian tube with hydrosalpinx. Detorsion of the tube was performed, and the tube was drained using diathermic incision. After the surgery, the patient recovered rapidly. Ultrasonic evaluation 38 days later showed an echogenic area measuring 2×3 cm suspected for persistent hydrosalpinx. Because of the asymptomatic postoperative period, the patient was treated conservatively, and no further treatment was performed.

Posttraumatic stress disorder related to postpartum haemorrhage: A systematic review.

In some cases childbirth leads to negative psychological responses such as posttraumatic stress disorder (PTSD). Postpartum hemorrhage (PPH) is a common and major complication of childbirth, which occasionally requires emergency hysterectomy in severe cases. Patients often describe these complications as a traumatic experience. It is unknown whether PPH is a risk factor for developing PTSD. In this systematic review we summarize the current knowledge about the association between PPH with or without emergency hysterectomy and posttraumatic stress symptoms or PTSD. If PPH is a risk factor for PTSD, this will allow adequate preventive measures with the aim to reduce the long-term effects and socioeconomic problems associated with PTSD. To conduct this review MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Library and PsycINFO databases were searched for publications between January 1986 and October 2017. Manuscripts evaluating the association between PPH and peripartum emergency hysterectomy and PTSD or posttraumatic stress symptoms were included. Fifty-two articles met the criteria for full-text review. Seven articles were included in this review. Five studies focused on the association between PPH and PTSD and two studies evaluated the association between emergency hysterectomy and PTSD. Three studies found no association between PPH and PTSD. Two studies reported a higher risk of developing PTSD or posttraumatic stress symptoms after PPH. Two studies reported a higher risk of developing PTSD after emergency hysterectomy. Meta-analysis was not possible due to the heterogeneity of these studies. Based on the results of these studies there may be an association between PPH and PTSD. Secondly, it seems likely that an association exists between emergency postpartum hysterectomy and PTSD, but the strength of this conclusion is limited by the small amount of studies included.