Local endometrial injury and IVF outcome: a systematic review and meta-analysis

A systematic review was conducted of the influence of local endometrial injury (LEI) on the outcome of the subsequent IVF cycle. MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI Conference Proceedings, ISRCTN Register and Meta-register were searched for randomized controlled trials to October 2011. The review included all trials comparing the outcome of IVF treatment in patients who had LEI in the cycle preceding their IVF treatment with controls in which endometrial injury was not performed. The main outcome measures were clinical pregnancy and live birth rates. In total, 901 participants were included in two randomized (n = 193) and six non-randomized controlled studies (n = 708). The quality of the studies was variable. Meta-analysis showed that clinical pregnancy rate was significantly improved after LEI in both the randomized (relative risk, RR, 2.63, 95% CI 1.39–4.96, P = 0.003) and non-randomized studies (RR 1.95, 95% CI 1.61–2.35, P < 0.00001). The improvement did not reach statistical significance in the one randomized study which reported the live birth rate (RR 2.29, 95% CI 0.86–6.11). Robust randomized trials comparing a standardized protocol of LEI before IVF treatment with no intervention in a well-defined patient population are needed.The endometrium is the lining of the womb where the embryo implants. Endometrial surface injury is a simple office procedure. We reviewed the literature to find out if performing endometrial surface injury before an IVF treatment cycle improves its outcome. Our review found that when endometrial surface injury was performed before an IVF treatment cycle, there was a significant improvement in the outcome of that treatment cycle. We recommend this question is addressed in a well-conducted randomized study to confirm the findings of our review.     

The use of vaginal natural progesterone for prevention of preterm birth in IVF/ICSI pregnancies

The aim of this study was to evaluate the effect of vaginal natural progesterone on the prevention of preterm birth in IVF/intracytoplasmic sperm injection (ICSI) pregnancies. A single-centre prospective placebo-controlled randomized study was performed. A total of 313 IVF/ICSI pregnant patients were randomized into two groups for either treatment with daily 400 mg vaginal natural progesterone or placebo, starting from mid-trimester up to 37 weeks or delivery. Amongst the patients, there were 215 singleton and 91 twin pregnancies. There was no significant difference in risk of preterm birth among all patients (OR 0.672, 95% CI 0.42–1.0. There was a significantly lower preterm birth rate in singleton pregnancies in the natural progesterone arm (OR 0.53, 95% CI 0.28–0.97) and no significant difference between both arms in twin pregnancies (OR 0.735, 95% CI 0.36–2). In conclusion, the administration of 400 mg vaginal natural progesterone from mid trimester reduced the incidence of preterm birth in singleton, but not in twin, IVF/ICSI pregnancies.Preterm labour is a major cause of perinatal and neonatal mortality and morbidity. It is defined as birth occurring prior to 37 weeks’ gestation; however, most damage occurs in infants born before 34 weeks. It was reported that pregnancies achieved by IVF or intracytoplasmic sperm injection (ICSI) are more liable to preterm labour. The objective of this study was to evaluate the effect of progesterone (given to the patient vaginally) on the prevention of preterm labour in IVF/ICSI pregnancies. Patients who became pregnant after IVF or ICSI were randomized into two groups. The first group was given 400 mg of vaginal progesterone starting from mid trimester until 37 weeks of pregnancy, and the second group received no treatment. The results showed that administration of 400 mg vaginal progesterone from mid trimester reduces the incidence of preterm labour in singleton, but not in twin, IVF/ICSI pregnancies.     

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n = 986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3–58.1%) for HP-HMG and 44.6% (40.2–49.0%) for rFSH (OR 1.44, 95% CI 1.12–1.85; P < 0.005). The mean costs per IVF treatment for HP-HMG and rFSH were £5393 (£5341–5449) and £6269 (£6210–6324), respectively (number needed to treat to fund one additional treatment was seven; P < 0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was £11,157 (£11,089–11,129) and £14,227 (£14,183–14,222) with rFSH (P < 0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis.     

Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF

This report aimed to examine the effects of atosiban on pregnancy outcome after IVF–embryo transfer. A prospective, randomized, placebo-controlled clinical study was performed. A total of 180 women undergoing intracytoplasmic sperm injection who had top-quality embryos were randomly allocated into treatment and control groups. All the patients had infertility due to tubal factor, hormonal-anovulatory disorders, male factor or unexplained reasons. The treatment group received intravenous administration of atosiban before embryo transfer with a total administered dose of 37.5 mg. In the control group, the same number of cycles was performed with placebo medication. The clinical pregnancy rate (PR) per cycle and implantation rate (IR) per transfer were 46.7% and 20.4% in the atosiban-treated group, which were significantly higher than in the control group (28.9% and 12.6%, respectively, P = 0.01). The miscarriage rates of groups 1 and 2 were 16.7% and 24.4%, respectively (P = 0.01). These results have indicated that atosiban increases the IR and PR after IVF–embryo transfer. These results suggest that atosiban treatment before embryo transfer is effective in priming of the uterus for implantation. This is the first study to investigate the possible contributions of atosiban for improving the PR after IVF–embryo transfer.     

Effectiveness of indometacin to prevent ovulation in modified natural-cycle IVF: A randomized controlled trial

Modified natural-cycle IVF has a lower pregnancy rate per started cycle as compared with IVF with ovarian stimulation due to, for example, premature ovulation. Indometacin administered before ovulation prevents follicle rupture. Therefore, addition of indometacin may improve the effectiveness of modified natural-cycle IVF. This double-blind, randomized, placebo-controlled trial with indometacin or placebo in 120 women aged 27–36 years compared the number of patients without premature ovulation as compared with the number of patients with one or more ovulations in a maximum of six cycles. Indometacin had no significant influence on the probability of a premature ovulation in patients during the six cycles (OR 2.38, 95% CI 0.94–6.04). A subgroup analysis showed a significant influence of indometacin in decreasing the probability of a premature ovulation in cycles without LH surge at the day of human chorionic gonadotrophin administration (OR 8.29, 95% CI 1.63–42.3, P = 0.009). Although this study could not detect a significantly lower ovulation rate in the indometacin group versus the placebo group, the data suggest that a subgroup of patients without LH surge prior to oocyte retrieval might benefit from indometacin in modified natural-cycle IVF.Modified natural-cycle IVF is a mild form of IVF, with a lower pregnancy rate per started cycle as compared with IVF with ovarian stimulation because of several unfavourable cycle events, such as ovulation before oocyte retrieval. Indometacin is a cheap drug, commonly used to reduce fever, pain and swelling caused by inflammation. It has been shown that indometacin administered before ovulation prevents this from happening. Therefore, it has been suggested that indometacin may improve the effectiveness of modified natural-cycle IVF. In this study, we assigned 120 women aged 27–36 years randomly to an indometacin group (60 women) and a group of women who used placebo (also 60 women). We evaluated whether indometacin could indeed prevent ovulation during a maximum of six modified natural-cycle IVF cycles. When we compared the two groups of women, indometacin did not seem to prevent ovulation compared with women who used placebo. Within these groups, however, the patients with a low level of LH (a hormone involved in ovulation) on the day that administration indometacin or placebo was started, indometacin did decrease the chance of an untimely ovulation. So although we could not detect a lower ovulation rate in the indometacin group versus the placebo group, our data suggest that a subgroup of patients with low LH concentrations prior to oocyte retrieval might benefit from indometacin in modified natural-cycle IVF.     

Preconditioning of sperm with sublethal nitrosative stress: a novel approach to improve frozen–thawed sperm function

Salpingectomy is the most widely used treatment for hydrosalpinx. The effect of salpingectomy on the stimulation response during subsequent IVF treatment, however, remains unclear. The aim of this systematic review was to evaluate the ovarian response and pregnancy outcome of IVF treatment carried out after salpingectomy compared with other pre-IVF treatment options for hydrosalpinx. We conducted a literature search using PubMed, Ovid MEDLINE, Google Scholar, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials. Five randomized studies and nine observational studies were included in the systematic review and evaluated using Cochrane Collaboration's tool for randomized, Newcastle–Ottawa scale for observational studies and GRADE guidelines for certainty of evidence assessment. The mean number of retrieved oocytes was similar between the groups in randomized (mean difference [MD] = –0.03, 95% CI –0.75 to 0.70) and observational studies (MD = –0.15, 95% CI –2.32 to 2.02). Live birth (RR 1.59, 95% CI 1.17 to 2.16), clinical pregnancy (RR 1.27, 95% CI 1.02 to 1.57) and implantation rates (RR 1.55, 95% CI 1.16 to 2.08) were higher in the salpingectomy group in randomized studies. The present systematic review and meta-analysis showed that salpingectomy does not impair the ovarian response during subsequent IVF treatment.     

Facteurs prédictifs de tolérance fœtale à la cordocentèse : étude rétrospective monocentrique

ObjectivesIndications for fetal blood sampling (FBS) are getting more limited. In this context, we aimed to evaluate fetal loss and morbidity associated with FBS and to precise the predictive parameters for fetal complications. More than a retrospective evaluation of our practices, the final end point of our study was to better inform the patients coming to our centre.Patients and methodsRetrospective monocentric cohort (Canadian Task Force classification II-2) of the 99 FBS performed between April 2004 and June 2010 on 80 fetuses, after excluding the procedures done for termination of pregnancy. The main clinical outcome was a composite outcome criteria for fetal tolerance including cesarean section for abnormal non stress test within the 24 hours, or any event responsible of a modified obstetrical management during the 14 day following FBS.ResultsMean maternal age at FBS was 30 years ± 5.13 SD and parity was 2.49 ± 1.38 SD. FBS was performed by an experienced operator in 86.5% of cases (CI 95%, 78–92.6); with a single insertion in 83.3% of circumstances (CI 95%, 74.4–90.2). The mean duration was 11 min ± 6.37 SD. The total rate of intrauterine death, in our series, was 7.1% (CI 95%, 2.9–14), including all reported fetal demise within the 14 days after FBS, whatever the relation with the procedure. Our study demonstrated a 9.1% occurrence of post-FBS altered CTG fetal testing (CI 95%, 4.2–16.6), half of it with spontaneous resolution. The rate of severe complications (main clinical outcome) was 11.1% (CI 95%, 5.7–19) including one fetal death liable to FBS and 10 emergency caesarean sections: 5.1% for fetal bradycardia (CI 95%, 1.7–11.4), 2% for placental abruption (CI 95%, 0.2–7.1), 2% for premature preterm rupture of membranes (CI 95%, 0.2–7.1) and 1% for significative umbilical cord bleeding (CI 95%, 0–5.5). Univariate factor analysis highlights 4 parameters for impaired fetal tolerance; a prolonged procedure, presence of low fetal platelets (< 30.10⁹/L); and FBS performed for fetal anaemia during Parvovirus B19 infection or allo-immune thrombocytopenia.Discussion and conclusionFBS remains a tricky procedure with a substantial risk of fetal loss or complications especially when performed on high-risk f?tuses. The length of the procedure should be shortened as much as possible (trained operator, postponed procedure when all favourable condition are not available). Fetal thrombocytopenia is a meaningful risk factor encouraging carefulness when exploring allo-immune fetal thrombocytopenia.     

Preeclampsia,gestational hypertension and subsequent hypothyroidism

ObjectivesTo evaluate the effect of preeclampsia (PE) and gestational hypertension (GH) on subsequent hypothyroidism. Recent studies suggest that women with PE have increased risk for reduced thyroid function, but the association between PE and GH with overt hypothyroidism has not been examined.Study designTwo prospective population-based cohort studies, the Northern Finland Birth Cohorts 1966 and 1986, followed women who had PE (N = 955), GH (N = 1449) or were normotensive (N = 13531) during pregnancy. Finnish national registers were used to confirm subsequent hypothyroidism. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) estimated hypothyroidism risk when comparing women with PE or GH with normotensive women.Main outcome measuresPrimary hypothyroidism during follow-up of 20–40 years.ResultsThe subsequent prevalence of hypothyroidism was higher among women with PE (4.0%) and GH (4.5%) compared with normotensive women (3.5%), but the risk increase was not significant (aHR for PE 1.13, 95% CI 0.80–1.59 and aHR for GH 1.11, 95% CI 0.85–1.45).Subgroup analysis among nulliparous women revealed a significant association between late PE and subsequent hypothyroidism (aHR 1.82, 95% CI 1.04–3.19).Early or recurrent PE was not associated with hypothyroidism (aHR 0.93, 95% CI 0.46–1.81 and aHR 1.35, 95% CI 0.63–2.88, respectively).ConclusionsOverall, PE or GH during pregnancy was not significantly associated with subsequent hypothyroidism in Finnish women after 20–40 years of follow-up. However, late PE in nulliparous women was associated with a 1.8-fold increased risk of subsequent hypothyroidism, a finding that merits further study in other populations.     

Higher live birth rate following transdermal testosterone pretreatment in poor responders: a systematic review and meta-analysis

A systematic review and meta-analysis was performed aiming to identify good-quality randomized controlled trials (RCT) evaluating testosterone pretreatment in poor responders. Eight RCTs were analysed, evaluating 797 women. Transdermal testosterone gel was used in all studies, with a dose ranging from 10 to 12.5 mg/day for 10–56 days. The main outcome measure was achievement of pregnancy, expressed as clinical pregnancy or live birth. Testosterone pretreatment was associated with a significantly higher live birth (risk ratio [RR] 2.07, 95% confidence interval [CI] 1.09–3.92) and clinical pregnancy rate (RR 2.25, 95% CI 1.54–3.30), as well as a significant increase in the number of cumulus–oocyte complexes retrieved. Significantly fewer days to complete ovarian stimulation, a lower total dose of gonadotrophins, a lower cancellation rate due to poor ovarian response and a thicker endometrium on the day of triggering of final oocyte maturation were observed. No significant differences were observed in oestradiol concentration, the numbers of follicles ≥17 mm, metaphase II oocytes, two-pronuclear oocytes and embryos transferred, and the proportion of patients with embryo transfer. The current study suggests that the probability of pregnancy is increased in poor responders pretreated with transdermal testosterone who are undergoing ovarian stimulation for IVF.     

The Effect of Gestational Weight Gain by Body Mass Index on Maternal and Neonatal Outcomes

ObjectiveTo evaluate the effects of gestational weight gain on maternal and neonatal outcomes in different body mass index (BMI) classes.MethodsWe compared maternal and neonatal outcomes based on gestational weight gain in underweight, normal weight, overweight, obese, and morbidly obese (BMI ≥ 40.00) women. The study group was a population-based cohort of women with singleton gestations who delivered between April 1, 2001, and March 31, 2007, drawn from the Newfoundland and Labrador Provincial Perinatal Program Database. Univariate analyses and multivariate logistic regression analyses (controlling for maternal age, parity, smoking status, partnered status, and gestational age) were performed and odds ratios (ORs) were calculated.ResultsOnly 30.6% of women gained the recommended amount of weight during pregnancy; 52.3% of women gained more than recommended, and 17.1% gained less than recommended. In women with normal pre-pregnancy BMI, excess weight gain was associated with increased rates of gestational hypertension (OR 1.27; 95% CI 1.08–1.49), augmentation of labour (OR 1.09; 95% CI 1.01–1.18), and birth weight ≥ 4000 g (OR 1.21; 95% CI 1.10–1.34). In overweight women, excess weight gain was associated with increased rates of gestational hypertension (OR 1.31; 95% CI 1.10–1.55) and birth weight ≥4000 g (OR 1.30; 95% CI 1.15–1.47). In women who were obese or morbidly obese, excess weight gain was associated with increased rates of birth weight ≥4000 g (OR 1.20; 95% CI 1.07–1.34) and neonatal metabolic abnormality (OR 1.31; 95% CI 1.00–1.70). In morbidly obese women, poor weight gain was associated with less use of epidural analgesia (OR 0.34; 95% CI 0.12–0.95). In women who were of normal weight, overweight, or obese, the rate of adverse outcome (Caesarean section, gestational hypertension, birth weight < 2500 g or birth weight ≥4000 g) was lower in women with recommended weight gain than in those with excess weight gain. Adverse outcomes were reduced in nulliparous morbidly obese women who had poor weight gain (OR 0.18; 95% CI 0.04–0.83).ConclusionThe effects of gestational weight gain on pregnancy outcome depend on the woman’s pre-pregnancy BMI. Pregnancy weight gains of 6.7–11.2 kg (15–25lb) in overweight and obese women, and less than 6.7 kg (15lb) in morbidly obese women are associated with a reduction in the risk of adverse outcome.     

Short versus extended progesterone supplementation for luteal phase support in fresh IVF cycles: a systematic review and meta-analysis

This review and meta-analysis aim to assess the effect of prolonged progesterone support on pregnancy outcomes in women undergoing fresh embryo transfer after IVF/intracytoplasmic sperm injection (ICSI). Two independent authors searched Embase, MEDLINE and grey literature from inception to January 2019 for randomized controlled trials (RCT) of prolonged progesterone support versus early cessation. Risk of bias was assessed. Outcome measures were live birth, miscarriage and ongoing pregnancy rate. The study was registered with PROSPERO (CRD42018088605). Seven trials involving 1627 participants were included: three reported live birth rate (672/830), seven the miscarriage rate (178/1627) and seven the ongoing pregnancy rate (1351/1627). Clinical outcomes were similar between early progesterone cessation versus progesterone continuation: live birth rate (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.88–1.00), miscarriage rate (RR 0.91, 95% CI 0.69–1.20) and ongoing pregnancy rate (RR 0.98, 95% CI 0.91–1.05). Ongoing pregnancy rates were similar when analyses were restricted to those with cessation of progesterone on the day of a positive human chorionic gonadotrophin (RR 0.93, 95% CI 0.83–1.06). This meta-analysis suggests that prolonged progesterone support may be unnecessary after fresh embryo transfer. Further larger RCT would be useful to corroborate and lead to standardized duration of progesterone luteal phase support across IVF/ICSI centres.     

Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women

Abstract

Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09–1.18) and live birth (RR: 1.08; 95% CI: 1.05–1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91–1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11?mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11?mm (adjusted RR: 1.23; 95% CI: 1.11–1.37) and significantly lower for the ≤7?mm group (adjusted RR: 0.64; 95% CI: 0.45–0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.     

Use of an oxytocin antagonist in in vitro fertilization-embryo transfer for women with repeated implantation failure: a retrospective study

ObjectiveThis retrospective study aimed to investigate the use of an oxytocin antagonist in improving the pregnancy outcome of in vitro fertilization–embryo transfer (IVF–ET) in patients with repeated implantation failure (RIF).Materials and MethodsA total of 150 infertile couples with RIF undergoing IVF–ET were divided into three groups. Patients who did not receive atosiban were used as controls (Group 1; n = 80). Forty patients received a single bolus dose (6.75 mg, 0.9 mL/vial) of atosiban before ET (Group 2), and 30 patients received a bolus dose of 6.75 mg atosiban followed by infusion at 18 mg/hr for 3 hours immediately after ET (Group 3).ResultsA significantly higher implantation rate (30.21%) was noted in Group 2 compared with Groups 1 and 3 (11.8% and 15.9%, respectively; p = 0.0006). The clinical pregnancy rate of Group 2 (37.5%) was significantly higher than that of Groups 1 (12.5%) and 3 (20%) (p = 0.0057). The live birth rate was significantly higher in Group 2 (35%) than in Groups 1 and 3 (10% and 16.67%, respectively; p = 0.0031).ConclusionThese results suggest that IVF–ET using lower dosage of atosiban may improve pregnancy outcomes of patients with RIF.     

Long-term follow up of couples initially randomized between immobilization and immediate mobilization subsequent to IUI

A previous randomized clinical trial compared immobilization for 15 min with immediate mobilization subsequent to intrauterine insemination (IUI) and showed higher ongoing pregnancy rates in couples immobilizing subsequent to IUI. The current study compared the long-term effectiveness of immobilization subsequent to IUI. All couples (n = 391) included in the trial were followed for 3 years after randomization and pregnancies and treatments were recorded. After the initial trial period, couples in both groups were offered treatment according to local protocol. The primary outcome was an ongoing pregnancy during the 3 years after the initial trial. In this time period, there were 143 ongoing pregnancies in the immobilization group (n = 199 couples) and 112 ongoing pregnancies in the immediate mobilization group (n = 192). The ongoing pregnancy rates were 72% and 58%, respectively (relative risk 1.2, 95% CI 1.1–1.4). The persistent significant difference in ongoing pregnancy rates underpins the importance of immobilization after IUI. There is no valid reason to withhold women from immobilizing for 15 min after IUI.     

Office hysteroscopy improves pregnancy rates following IVF

The aim of the study was to evaluate the effect of office hysteroscopy (OH) on pregnancy rate in patients undergoing IVF. A total of 1258 patients attending an IVF clinic with normal hysteroscopic findings were enrolled. The impact of timing of OH before embryo transfer on pregnancy rate was investigated. The women were evaluated in three groups: group 1, OH performed 50 days or less before embryo transfer (n = 407), group 2, OH between 51 days to 6 months, (n = 280) and group 3, OH more than 6 months before embryo transfer (n = 571). The implantation rates were 22.1%, 16.1% and 11.1% in groups 1, 2 and 3, respectively. Overall pregnancy rates were 48.2%, 38.9% and 29.9% in groups 1, 2 and 3, respectively. The clinical pregnancy rates were 45.2%, 34.3% and 27.1% and the live birth rates were 36.9%, 27.9% and 22.6%, respectively. Implantation, pregnancy, clinical pregnancy and live birth rates were significantly higher in group 1 compared with groups 2 and 3 (all P < 0.05). OH may improve pregnancy rates, but timing of the procedure is important. The endometrial effect is highest when hysteroscopy is performed 50 days or less before embryo transfer.Office hysteroscopy (OH), which helps the clinician for the evaluation of the uterine cavity before IVF treatment, may affect the pregnancy rates depending on when the procedure is performed. A total of 1258 patients attending an outpatient IVF clinic were enrolled in the study. The women were evaluated in three groups: group 1, OH performed 50 days or less before embryo transfer (n = 407), group 2, OH between 51 days to 6 months, (n = 280) and group 3, OH more than 6 months before embryo transfer (n = 571). The implantation, pregnancy and clinical pregnancy rates were significantly higher in group 1 compared with groups 2 and 3. OH may improve pregnancy rates when performed 50 days or less before embryo transfer.     

Impact of obesity on reproductive outcomes after ovarian ablative therapy in PCOS: a collaborative meta-analysis

Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on reproductive outcomes after ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. This systematic review and meta-analysis assessed the strength of the association between obesity and ovulation or pregnancy rates after OAT. MEDLINE and several other databases were searched from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the relative risk of reproductive outcomes (ovulation and pregnancy) in lean (body mass index <25 kg/m²) compared with overweight or obese women. The study obtained 15 data sets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22–1.66) compared with obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39–2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. It is concluded that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively.Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. We therefore undertook a systematic review and meta-analysis to assess the strength of the association between obesity and ovulation or pregnancy rates after OAT. We searched MEDLINE and several other databases from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the risk ratio of reproductive outcomes (ovulation and pregnancy) in lean (BMI <25 kg/m²) as opposed to overweight or obese women. We obtained 15 datasets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22–1.66) as compared to obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39–2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. We conclude that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively.     

Erectile Dysfunction and Risk of Clinical Cardiovascular Events: A Meta-Analysis of Seven Cohort Studies

IntroductionFor many years, erectile dysfunction (ED) has been considered as a complication of cardiovascular disease (CVD) or regarded as a late consequence of generalized arterial disease. However, a growing body of evidence suggests that ED is an early manifestation of atherosclerosis and a precursor to systemic vascular disease.AimWe conducted a meta-analysis to evaluate the association between ED and the risk of CVD events.MethodsRelevant studies published between January 1966 and September 2009 were identified by searching Medline, Embase, and The Cochrane Library. Studies were selected using a prior defined criteria. The strength of the relationship between ED and CVD events was assessed by adjusted relative risks (RRs).Main Outcome MeasuresThe adjusted RRs of CVD events.ResultsA total of 45,558 participants from seven cohort studies (eight full-text articles) were identified in this meta-analysis. The studies provided adjusted RRs estimates for ED subjects comparing with health subjects, leading to a pooled adjusted RR of 1.47 (95% confidence interval [CI], 1.29–1.66, P < 0.001; P for heterogeneity = 0.152; I² = 36.2%) for CVD events. The risks of CVD, all-cause mortality and myocardial infarction were 1.41 (95% CI, 1.22–1.64 P < 0.001), 1.23 (95% CI, 1.02–1.48; P = 0.034), and 1.43 (95% CI, 1.10–1.85 P = 0.007), respectively. The overall adjusted RR decreased significant from 1.63 (<7 years) to 1.37 (≥7 years) along with the elongation of follow-up.ConclusionsThere is evidence of an increased risk of CVD events for patients with ED. Patients who are discovered to have ED are supposed to be thoroughly assessed for cardiovascular risk and occult systemic vascular disease. Guo W, Liao C, Zou Y, Li F, Li T, Zhou Q, Cao Y, and Mao X. Erectile dysfunction and risk of clinical cardiovascular events: A meta-analysis of seven cohort studies.     

Ovarian reserve and PGD treatment outcome in women with myotonic dystrophy

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. There are conflicting reports about its effect on female fertility. This study investigated ovarian reserve and IVF–preimplantation genetic diagnosis (PGD) outcome in women with DM1. A total of 21 women undergoing PGD for DM1 were compared with 21 age- and body mass index-matched women undergoing PGD for other diseases. Ovarian reserve markers, response to stimulation, embryo quality and clinical pregnancy and live birth rates were compared. Day-3 FSH concentration was higher, while anti-Müllerian hormone concentration and antral follicle count were lower in the DM1 group (median, range: 6.9 (1.8–11.3) versus 5.7 (1.5–10.7) IU/l; 0.9 (0.17–5.96) versus 2.68 (0.5–9.1) ng/ml; and 13 (0–63) versus 23 (8–40) follicles, respectively, all P < 0.05). Total FSH dose was higher (5200 versus 2250 IU, P = 0.004), while the numbers of oocytes retrieved (10 versus 16, P < 0.04) and metaphase-II oocytes (9 versus 12, P < 0.03) were lower in the DM1 group. The number of cycles with top-quality embryos and the clinical pregnancy rate were lower in the DM1 group. In conclusion, there is evidence of diminished ovarian reserve and less favourable IVF–PGD outcome in women with DM1.Myotonic Dystrophy (DM) is the most common form of muscular dystrophy in adults. There is evidence of subfertility in males affected with the disease but conflicting reports about the effect of the disease on female fertility. The aim of our study was to investigate ovarian reserve and IVF–PGD results in women with DM. Twenty-one women undergoing preimplantation genetic diagnosis (PGD) treatment for DM were compared to 21 age- and BMI matched women undergoing PGD treatment for other diseases. The two groups were compared for antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) levels (the best known markers of ovarian reserve and fertility potential), ovarian response, embryo quality and pregnancy and live birth rates. AFC and the AMH levels were statistically significant lower in the DM group. Total medication dose needed for ovarian stimulation was higher, the number of oocytes and mature oocytes retrieved, and the number of cycles with top quality embryos were lower in the DM group compared to the controls. In conclusion, there is evidence of diminished ovarian reserve, and less favorable IVF-PGD outcome in women with DM. Therefore, we recommend advising these women about the possibility of early decreasing ovarian function in order to prevent any delay in reproductive planning.     

Maternal and Perinatal Outcomes of Extreme Obesity in Pregnancy

ObjectiveTo evaluate the effects of extreme obesity (pre-pregnancy BMI ≥ 50.0 kg/m²) in pregnancy on maternal and perinatal outcomes.MethodsWe conducted a population-based cohort study using the Newfoundland and Labrador Perinatal Database to compare obstetric outcomes in women with extreme obesity and those with a normal BMI (pre-pregnancy BMI 18.50 to 24.99 kg/m²). We included women with singleton gestations who gave birth between January 1, 2002, and December 31, 2011. Maternal outcomes of interest included gestational hypertension, gestational diabetes, Caesarean section, shoulder dystocia, length of hospital stay, maternal ICU admission, postpartum hemorrhage, and death. Perinatal outcomes included birth weight, preterm birth, Apgar score, neonatal metabolic abnormality, NICU admission, stillbirth, and neonatal death. A composite morbidity outcome was developed including at least one of Caesarean section, gestational hypertension, birth weight ≥ 4000 g, birth weight < 2500 g, or NICU admission. Univariate analyses and multivariate logistic regression analyses (controlling for maternal age, parity, smoking, partner status, and gestational age) were performed, and adjusted odds ratios (aORs) and 95% confidence intervals were calculated.ResultsA total of 5788 women were included in the study: 71 with extreme obesity and 5717 with a normal BMI. Extremely obese women were more likely to have gestational hypertension (19.7% vs.4.8%) (aOR 1.56; 95% CI 1.33 to 1.82), gestational diabetes (21.1% vs.1.5%) (aOR 2.04; 95% CI 1.74 to 2.38), shoulder dystocia (7.1% vs.1.4%) (aOR 1.51; 95% CI 1.05 to 2.19), Caesarean section (60.6% vs.25.0%) (aOR 1.46; 95% CI 1.29 to 1.65), length of hospital stay more than five days (excluding Caesarean section) (14.3% vs.4.7%) (aOR 1.42; 95% CI 1.07 to 1.89), birth weight ≥ 4000 g (38.0% vs. 11.9%) (aOR 1.58; 95% CI 1.38 to 1.80), birth weight ≥ 4500 g (16.9% vs.2.1%) (aOR 1.87; 95% CI 1.57 to 2.23), neonatal metabolic abnormality (8.5% vs.2.0%) (aOR 1.50; 95% CI 1.20 to 1.86), NICU admission (16.9% vs.7.8%) (aOR 1.28; 95% CI 1.07 to 1.52), stillbirth (1.4% vs.0.2%) (aOR 1.68; 95% CI 1.00 to 2.82) and composite adverse outcome (81.7% vs.41.5%) (aOR 1.57; 95% CI 1.35 to 1.83).ConclusionWomen with extreme obesity have increased risks of a variety of adverse maternal and perinatal outcomes. As approximately 6 per 1000 women giving birth in our population have extreme obesity, it is important to address these risks pre-conceptually and encourage a healthier BMI before pregnancy.     

Follicle recruitment determines IVF productivity rate via the number of embryos frozen and subsequent transfers

IVF productivity rate is an index defined as the sum of all live births from either fresh or frozen embryo transfers arising from a single oocyte collection. This retrospective analysis over 9 continuous years used this index to understand the potential impact on pregnancy rates of milder stimulation regimens with associated reduced egg numbers. The productivity rate per collection increased in a linear and significant rate as more oocytes were recovered, more embryos frozen and more frozen embryo transfers contributed to pregnancy. This observation was true for women aged <35 years and less so for women aged 35–39 years but not for women aged 40 years and older. The contribution of frozen embryo transfer to the productivity rate rose in a linear manner, reaching over 40% of all live births with nine oocytes. The number of live births per oocyte, pronuclear embryos and thawed embryos decreased significantly but the number of live births per embryo transferred (fresh or frozen) rose with rising oocyte numbers, reflecting increasing opportunity for embryo selection. This study suggests that optimal benefits with minimal risks are gained from a model that includes both fresh and frozen transfers under stimulation generating between 8 and 12 eggs.Most of the costs and risks associated with an IVF cycle occur during the stimulation, egg collection and subsequent transfer of fresh embryos and ignore or treat separately the outcome from any subsequent frozen embryo transfers. We have used the term ‘productivity rate’ (or cumulative pregnancy rate per collection cycle) that includes outcomes from both fresh and frozen transfers as a tool to explore the impact of oocyte numbers on the ultimate chance of pregnancy. While the pregnancy rate for individual fresh and frozen transfers were largely unrelated to oocyte numbers, the cumulative chance of pregnancy rose significantly with the number of oocytes recovered. This was due to the increasing contribution of frozen embryo transfers to the overall chance of pregnancy producing more than half of all pregnancies above five oocytes. While the fertilization rate and embryo quality was independent of egg numbers, increasingly more embryos needed to be used to generate sufficient good-quality embryos for transfers as the egg numbers rose. The study found that 8–12 oocytes provided the highest cumulative chance of pregnancy with the least risk of either failed fertilization or ovarian hyperstimulation syndrome and this range could be used as a target number for individualized stimulation regimens.