M. Aboulghar

Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review.

Gonadotrophin-releasing hormone (GnRH) antagonists suppress gonadotrophin secretion resulting in dramatic reduction in treatment cycle duration. Assuming comparable clinical outcomes, these benefits may justify changing the standard long GnRH agonist protocol to GnRH antagonist regimens. To evaluate the evidence, databases (e.g. Cochrane Library, MEDLINE, EMBASE) were electronically searched, hand searches were performed, and manufacturers in the field were contacted. Twenty-seven randomized controlled trials (RCT) fulfilled inclusion criteria for comparison of GnRH antagonist with long GnRH agonist protocol. Clinical pregnancy rate and ongoing pregnancy/live-birth rate were significantly lower in the antagonist group (P = 0.009; OR = 0.83, 95% CI 0.72-0.95 and P = 0.02; OR = 0.82, 95% CI 0.68-0.97 respectively). Conversely, incidence of severe OHSS was significantly reduced with the antagonist protocol (P = 0.01; OR = 0.60, 95% CI 0.40-0.88), and interventions to prevent OHSS were administered more frequently in the agonist group (P = 0.03; OR = 0.43, 95% CI 0.20-0.92). Concluding, GnRH antagonist protocols are short, simple, with good clinical outcomes and significant reduction in severe OHSS incidence and gonadotrophin amount; however, the lower pregnancy rate compared with the GnRH agonist long protocol necessitates counselling subfertile couples before recommending change from GnRH agonist to antagonist.

13–14‐week fetal anatomy scan: a 5‐year prospective study

To assess the potential value of an early (first‐trimester) ultrasound examination in depicting fetal anomalies by transabdominal (TAS) and transvaginal (TVS) sonography, to compare it with the traditional mid‐trimester anomaly ultrasound examination and to evaluate the degree of patient acceptance of early sonography by the transvaginal route.

A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS.

This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group.

Paternal age and outcome of intracytoplasmic sperm injection.

In a retrospective study, the outcome of intracytoplasmic sperm injection (ICSI) in two age groups of men was studied. Couples with male partners aged 50 years and over (group A) (n = 227) with mean age of 53 +/- 5 years were compared with couples with younger age-group male partners (group B) (n = 227) with a mean age of 38.4 +/- 5.8 years. The control group of younger men was selected so that the womens age matched between the two groups. There was no significant difference in pregnancy rate between the two groups (37.9 versus 36.6%; OR = 1.06, 95% CI = 0.72-1.55). There was also no significant difference in the pregnancy rate between men aged 60 years and over as compared with men aged 50 to 59 years (OR = 1.00, 95% CI 0.74-1.37). However, the long-term outcome of these pregnancies needs further investigation. Semen analysis showed significantly lower motility in group A (37.4 +/- 20.4) versus group B (46.4 +/- 15.5; P < 0.0001). There was a significantly higher fertilization rate in younger men (P < 0.0001; OR = 1.36, 95% CI = 1.19-1.55), but this did not affect the pregnancy rate. In conclusion, it appears that paternal age has no effect on the pregnancy rate after ICSI.

Prospective randomized study comparing luteal phase support for ICSI patients up to the first ultrasound compared with an additional three weeks

BACKGROUND There is a consensus that administration of progesterone to women after IVF for luteal phase support (LPS) is associated with a higher ongoing pregnancy rate. However there are few studies, including only one randomized study, which have examined the optimal duration of LPS. METHODS A questionnaire concerning details of LPS was returned from 21 leading IVF centres. We then randomized 257 women, who were pregnant after ICSI on day of first ultrasound, into two groups: to continue LPS for three more weeks or to stop on the day of ultrasound. RESULTS The duration of LPS in the questionnaire varied from the day of positive pregnancy test up to 12 weeks of pregnancy in different centres. In the randomized study, 132 patients in Group A continued LPS for 3 weeks after first ultrasound, whereas 125 patients in Group B stopped LPS on day of first ultrasound. After confirming pulsations, the miscarriage rate up to 20 weeks of gestation was 4.6% (6/132) in group A and 4.8% (6/125) in group B [odds ratios (OR) = 0.94; 95% confidence intervals (CI) = 0.3-3.1]. Bleeding episodes were 15.9% in Group A compared with 20.8% in group B (OR = 0.72; 95% CI = 0.38-1.36). CONCLUSIONS There is no international consensus about the duration of LPS; our single-centre randomized trial did not support extending the LPS beyond the day of first ultrasound demonstrating echoes and pulsations. Trials registry number-ISRCTN: 88722916.

Increasing the dose of human menopausal gonadotrophins on day of GnRH antagonist administration: randomized controlled trial

A significantly lower pregnancy rate following the gonadotrophin-releasing hormone (GnRH) antagonist protocol as compared with the long GnRH agonist protocol has been reported. The objective of this study was to investigate whether increasing the dose of gonadotrophins on the day of antagonist administration would increase the pregnancy rate. This study is an open labelled, randomized controlled trial and allocation was done using sealed envelopes. One hundred and fifty-one subfertile couples undergoing IVF/intracytoplasmic sperm injection (ICSI) cycles were included in the study. Ovarian stimulation was started on day 3 of the cycle, using 150-300 IU human menopausal gonadotrophin (HMG)/day. From day 8 onward, daily vaginal ultrasound and daily urinary LH estimation were performed. If a premature LH rise was detected, the cycle was cancelled. The antagonist (0.25 mg daily) was started when the leading follicle reached 15 mm in mean diameter and LH testing in urine was negative up to and including the day of human chorionic gonadotrophin (HCG) injection. Patients were randomized on the day of starting the antagonist into two groups: group A, 72 patients with no increase in HMG dose, and group B, 79 patients in whom the dose of HMG was increased by 75 IU on the day of antagonist administration, and continued till the day of HCG administration. The results showed no statistically significant difference between the groups regarding number of oocytes retrieved, embryos obtained, implantation rate, clinical pregnancy rate and multiple pregnancy rate. It was concluded that there is no clinical evidence for increasing the dose of HMG on the day of antagonist administration.

Analysis of 2,386 consecutive cycles of in vitro fertilization or intracytoplasmic sperm injection using autologous oocytes in women aged 40 years and above

OBJECTIVE To estimate the live-birth and miscarriage rates in 1-year age increments for women aged ≥40 years undergoing in vitro fertilization or intracytoplasmic sperm injection (ICSI-IVF) with autologous oocytes. DESIGN Retrospective database and chart analysis. SETTING Egyptian IVF and embryo transfer center. PATIENT(S) One thousand six hundred forty-five women aged ≥40 years undergoing 2004 fresh nondonor IVF-ICSI cycles. INTERVENTION(S) ICSI-IVF using ejaculate or surgically retrieved sperm. MAIN OUTCOME MEASURE(S) Pregnancy and live-birth rates per initiated cycle based on 1-year age increments. RESULT(S) The overall live-birth rate per initiated cycle was 6.7% (range: 10% to 0.5%). The pregnancy loss rate was 44.8% (range: 39.0% to 75.0%). The cutoff age was 43 years, when the pregnancy rate became statistically significantly lower. The live-birth rate per initiated cycle was statistically significantly higher for women <43 years old, 132 out of 1766 (7.4%) compared with women ≥43 years old, 7 out of 620 (1.1%). The miscarriage rate was 127 out of 295 (43.1%) compared with 15 out of 23 (65.2%) for the two age groups, respectively. CONCLUSION(S) The success rate of ICSI-IVF as measured by live-birth rate per initiated cycle was statistically significantly higher for women aged <43 years as compared with women aged ≥43 years. Once women have attained age 43 years, alternative methods such as oocyte donation cycles or previously cryopreserved embryos are likely to be more effective.

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.

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Objective To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Cochrane databases (until December 2015). Review methods Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks’ gestation. Results 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks’ gestation (risk difference 1.2/1000, 95% confidence interval −1.3 to 3.6; I2=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I2=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (−12.4 to 17.4/1000; I2=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies. Conclusions To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks’ gestation; in monochorionic pregnancies delivery should be considered at 36 weeks. Systematic review registration PROSPERO CRD42014007538.

Pregnancy rate is not improved by delaying embryo transfer from days 2 to 3

OBJECTIVE To compare the outcome of assisted reproduction in day 2 versus day three embryo transfer. DESIGN Prospective study. PARTICIPANTS A total of 927 consecutive embryo transfers for IVF and ICSI cycles including 626 embryo transfers on day 2 and 301 on day 3. INTERVENTION IVF and ICSI. OUTCOME MEASURE Clinical pregnancy rate. RESULTS There is no significant difference in the pregnancy rate between ET on day 2 (50.9%) and ET on day 3 (50.5%). CONCLUSION Embryo transfer could be done on days 2 or 3 according to the convenience of the patient and the medical team. CONDENSATION Embryo transfer could be done on days 2 or 3 according to the convenience of the medical team with similar results.