Hesham Al-Inany

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.

Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis.

OBJECTIVE To determine whether gonadotropin-releasing hormone (GnRH) analog cotreatment with chemotherapy provides better reproductive outcomes for women at risk of premature ovarian failure (POF) as a side-effect of gonadotoxic chemotherapy. DESIGN Systematic review and meta-analysis. SETTING University-affiliated research centers. PATIENT(S) None. INTERVENTION(S) Electronic and manual searches (e.g., MEDLINE, EMBASE, CENTRAL) up to January 2010 were performed to identify randomized controlled trials (RCTs) comparing GnRH cotreatment with chemotherapy alone in premenopausal women. MAIN OUTCOME MEASURE(S) Incidence of POF after treatment, incidence of women with resumption of ovulation, POF after an initial normal cycle, normal cycles but abnormal markers of ovarian reserve, spontaneous occurrence of pregnancy after treatment, and time to reestablishment of menstruation; data also extracted to allow for an intention-to-treat analysis. RESULT(S) Twenty-eight RCTs were identified, but only six met the inclusion criteria. Data were only available for the incidence of women with new onset of POF, resumption of ovulation, and occurrence of pregnancy. The incidence of POF or resumption of ovulation both demonstrated a statistically significant difference in favor of the GnRH cotreatment. The occurrence of spontaneous pregnancy showed no statistically significant difference between GnRH cotreatment and the control groups. CONCLUSION(S) Evidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, with higher rates of spontaneous resumption of menses and ovulation but not improvement in pregnancy rates. Data relating to study quality and possible bias for the majority of the outcomes in this review were not available, denoting possible selective reporting of trial data.

A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection.

OBJECTIVE To compare the karyotype of babies conceived through ICSI with that of naturally conceived babies. DESIGN Prospective controlled study. SETTING The Egyptian IVF-ET Center, Cairo, Egypt. PATIENT(S) Four hundred and thirty babies conceived through ICSI and 430 babies conceived naturally. INTERVENTION(S) ICSI and karyotyping. MAIN OUTCOME MEASURE(S) Abnormal karyotype. RESULT(S) Four hundred and thirty consecutive babies conceived through ICSI who were delivered in one hospital had 15 abnormal karyotypes (3.5%). Of the 15 babies, 7 were of female phenotype and 8 of male phenotype. Six babies had sex chromosome anomalies, 8 had autosomal anomalies, and 1 had combined sex chromosome and autosomal anomalies. A control group of 430 consecutive babies conceived naturally who were delivered in one hospital had no abnormal karyotype. The difference between the two groups was significant (P<.001). CONCLUSION(S) ICSI carries a small but significant increased risk of abnormal karyotyping to the offspring. This risk appears to be equally distributed between autosomal and sex chromosome anomalies.

Metformin reduces abortion in pregnant women with polycystic ovary syndrome.

Background. Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin – owing to its metabolic, endocrine, vascular and anti-inflammatory effects – may reduce the incidence of first-trimester abortion in PCOS women. Materials and methods. A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000–2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group. Results. Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11–0.42). Conclusions. Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.

Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis

BACKGROUND Recently, dopamine agonists were proposed as a prophylactic treatment for ovarian hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment cycles. METHODS We conducted a systematic review and meta-analysis of randomized trials comparing the prophylactic effect of the dopamine agonist, cabergoline, versus no treatment in IVF/ICSI cycles. Primary outcome was OHSS incidence per randomized woman. Secondary outcomes were live birth rate, ongoing pregnancy rate, clinical pregnancy rate and miscarriage rate. Searches (until September 2009) were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts. RESULTS Four randomized trials entailing 570 women were included. There was evidence of a statistically significant reduction in the incidence of OHSS in the cabergoline group (OR 0.41, 95% CI 0.25-0.66) with an absolute risk reduction of 12% (95% CI 6.1-18.2%), but there was no statistically significant evidence of a reduction in severe OHSS (OR 0.50, 95% CI 0.20-1.26). There was no evidence for a difference in clinical pregnancy rate (OR 1.07, 95% CI 0.70-1.62) and miscarriage rate (OR 0.31, 95% CI 0.03-3.07). CONCLUSION Prophylactic treatment with the dopamine agonist, cabergoline, reduces the incidence, but not the severity of OHSS, without compromising pregnancy outcomes.

Embryo culture media and IVF/ICSI success rates: a systematic review

BACKGROUND The media that are used to culture human preimplantation embryos are considered to be an important factor for the success rates of IVF/ICSI. Here, we present a systematic review of randomized controlled trials (RCTs) on the effect of culture media on IVF/ICSI success rates. METHODS RCTs published between January 1985 and July 2012 were eligible for inclusion. The primary outcome was live birth. Secondary outcomes were health of babies born, ongoing pregnancies, clinical pregnancies, miscarriages, multiple pregnancies, implantation rate, cryopreservation rate, embryo quality and fertilization rate. For those media that were evaluated in more than one comparison, an unconventional meta-analysis was performed by pooling the data of the media they were compared to. RESULTS Twenty-two RCTs were included that evaluated 31 different comparisons. Conventional meta-analysis was not possible for any of the outcomes as nearly all trials compared different culture media. Only four trials reported on live birth, and one of them reported a significant difference. Nine trials reported on ongoing and/or clinical pregnancy rates, of which four showed a significant difference. Pooling the data did not reveal a superior culture medium. CONCLUSIONS It is yet unknown what culture medium leads to the best success rates in IVF/ICSI. Given the potential importance of culture media for treatment outcome, rigorously designed RCTs are needed for currently available, as well as newly introduced culture media.

Efficacy and safety of human menopausal gonadotrophins versus recombinant FSH: a meta-analysis

LH activity has been proposed to influence treatment response and outcome. In order to assess its clinical profile and efficacy, human menopausal gonadotrophin (HMG) was compared with recombinant FSH (r-FSH) in IVF/intracytoplasmic sperm injection (ICSI) cycles. Computerized and hand searches were conducted for relevant citations. Primary outcome measures were live-birth and OHSS rates. Secondary outcomes were clinical pregnancy, multiple pregnancy, miscarriage rates and cycle characteristics. The live-birth rate was significantly higher with HMG [odds ratio (OR) = 1.20, 95% CI = 1.01-1.42] versus r-FSH, but OHSS rates (OR = 1.21, 95% CI = 0.78-1.86) were not significantly different. As for the secondary outcomes, there was statistical significance with regard to the clinical pregnancy rate also in favour of the HMG group. Even so, there were significantly fewer treatment days, total dose and embryos produced in the r-FSH group compared with the HMG group. The other secondary outcomes were not different between the two groups. In conclusion, HMG has been demonstrated to be superior to r-FSH with regard to the clinical outcomes, with equivalent patient safety during assisted reproduction.

GnRH antagonists are safer than agonists: an update of a Cochrane review

GnRH agonists or antagonists can be used to prevent LH surges duringovarian stimulation for assisted reproduction. GnRH agonists down-regulate GnRH pituitary receptors. GnRH antagonists directly andrapidly inhibit gonadotrophin release. In a 2006 systematic review invol-ving 29 trials, the average clinical pregnancy rate was 4.7% lower withGnRH antagonist treatment and the incidence of ovarian hyperstimula-tion syndrome (OHSS) was 2% lower compared with GnRH agonisttreatment (Al-Inany et al.,2006). The current update includes 45trials which addressed live birth or ongoing pregnancy rate (OPR) inGnRH antagonist and GnRH agonist protocols among women under-going assisted reproduction treatment (Youssef et al.,2011).

Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible protocol

A meta-analysis was conducted to investigate whether flexible gonadotrophin-releasing hormone (GnRH) antagonist administration according to follicular size would be more beneficial than starting on a fixed day. Only randomized controlled trials were included after a comprehensive search strategy. The data were combined for meta-analysis with RevMan software. Eleven trials were identified, but only four randomized controlled trials met the inclusion criteria. There was no statistically significant difference in pregnancy rate per woman randomized, although there was a trend towards a higher pregnancy rate with the fixed protocol, especially with delayed administration beyond day 8 [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.45-1.1]. There was no premature LH surge in any participant in either protocol. However, there was a statistically significant reduction both in number of antagonist ampoules (OR -1.2 95%, CI -1.26 to -1.15) and amount of gonadotrophin (OR 95.5 IU, 95% CI 74.8-116.1) used in the flexible protocol. In conclusion, there was no statistically significant difference in pregnancy rate between flexible and fixed protocols. There was a statistically significant reduction in the amount of recombinant FSH with the flexible protocol.

Diagnosis and management of unexplained infertility: an update

Abstract. Unexplained infertility constitutes around 15% of patients presenting with infertility. A lack of agreement exists among infertility specialists with regard to the diagnostic tests to be performed and their prognostic value as well as criteria of normality. It seems that serum progesterone for detection of ovulation, hysterosalpingography and or laparoscopy for tubal patency and semen analysis are the basic tests for diagnosis of unexplained infertility. Expectant treatment is the option of choice for young patients with short period of infertility. The spontaneous pregnancy rate is very high in this group of patients. The world literature have shown that controlled ovarian hyperstimulation and intrauterine insemination (COH and IUI) is an effective treatment of unexplained infertility. According to the available data, this procedure could be limited to three trials. There is evidence that both COH and IUI are important independent positive factors in achieving better pregnancy rate in unexplained infertility. If the above measures fail to achieve pregnancy, GIFT or IVF/ICSI could be performed as it yields a high pregnancy rate.