Search

Objective To evaluate the evidence addressing the association between the use of ovarian stimulation drugs and the risk of breast cancer. Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Women without any previous history of breast cancer undergoing ovarian stimulation. Intervention(s) Electronic databases were searched from 1990 until January 2020. All cohort studies reporting new incidences of breast cancer in infertile women using ovarian stimulating drugs were included. Treated (exposed) infertile women were compared with the unexposed general population with unexposed infertile women as controls. Main Outcome Measure(s) New diagnosis of breast cancer within an infertile and general population after exposure to ovarian stimulation drugs. Result(s) Overall, the quality of evidence was very low because of the serious risk of bias and indirectness (nonrandomized studies). There was no significant increase in the risk of breast cancer among women treated with any ovarian stimulation drug for infertility compared with that in unexposed controls from the general population and the infertile population (pooled odds ratio 1.03, 95% Confidence interval 0.86 to 1.23, 20 studies, I2 = 88.41%, very low quality of evidence). Furthermore, no significant increase in the risk of breast cancer was found with the use of clomiphene citrate or gonadotropins, alone or in combination. Conclusion(s) The current study found that the use of clomiphene citrate and gonadotropins in infertile women was not associated with an increased risk of breast cancer.

Pregnancies resulting from assisted reproductive techniques are at higher risk of adverse perinatal outcomes compared with spontaneous conceptions. Underlying infertility and IVF procedures have been linked to adverse perinatal outcomes. It is important to know if ovarian stimulation influences perinatal outcomes after IVF. A systematic search for relevant studies was conducted up to November 2016 on the following databases: PubMed, EMBASE, DARE and Cochrane Central Register of Controlled Trials. Perinatal outcomes included preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), large for gestational age (LGA) and congenital anomalies. Data from four studies, which included a total of 96,996 and 704 singleton live births after stimulated IVF and natural or modified natural cycle IVF, were included in the meta-analysis. The risk of PTB (RR 1.27, 95% CI 1.03 to 1.58) and LBW (RR 1.95, 95% CI 1.03 to 3.67) were significantly higher after stimulated compared with natural or modified natural cycle IVF. Data from one study were available for SGA, LGA, congenital anomalies and no significant differences were reported between the groups. This study suggests a higher risk of PTB and LBW after stimulated IVF compared with natural or modified natural IVF, although the absolute increase in risk may be low.

A higher risk of pregnancy complications occurs after assisted reproductive techniques compared with spontaneously conceived pregnancies. This is attributed to the underlying infertility and assisted reproduction technique procedures involved during treatment. It is a matter of interest whether use of donor oocytes affects perinatal outcomes compared with pregnancies after autologous IVF. Anonymized data were obtained from the Human Fertilization and Embryology Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF live births. Data from all women who underwent donor oocyte recipient or autologous IVF cycles, both followed with fresh embryo transfer, were analysed to compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after singleton and multiple live births. The risk of adverse perinatal outcomes after oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after oocyte donation compared with autologous IVF singletons. The adjusted odds PTB (aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation compared with autologous IVF multiple births. Analysis of this large dataset suggests significantly higher risk of PTB and LBW after ooctye donation compared with autologous IVF pregnancies.

Objective To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF. Design Randomized controlled trial. Setting Tertiary referral fertility units. Patient(s) Women with previous poor ovarian response undergoing IVF. Intervention(s) One hundred eleven women were randomized to the long GnRH agonist, short agonist, and antagonist regimens. Main Outcome Measure(s) The primary outcome was the number of oocytes retrieved. Secondary outcome measures were gonadotropin consumption, duration of stimulation, cycle cancellation rate, mature oocytes retrieved, fertilization rate, cycles reaching ET, and clinical and ongoing pregnancy rates. Result(s) Number of oocytes retrieved was significantly higher with long GnRH agonist compared with the short agonist regimen (4.42 ± 3.06 vs. 2.71 ± 1.60), while there was no significant difference between long agonist and antagonist regimens (4.42 ± 3.06 vs. 3.30 ± 2.91). Duration of stimulation and total gonadotropin dose were significantly higher with long agonist compared with short agonist and antagonist regimens. The ongoing pregnancy rate was 8.1% with long and short agonist regimens and 16.2% with the antagonist regimen. Conclusion(s) Long GnRH agonist and antagonist regimens offer a suitable choice for poor responders, whereas the short agonist regimen may be less effective because of fewer eggs retrieved.

This systematic review and meta-analysis investigated whether gonadotrophin-releasing hormone (GnRH) antagonist protocols reduce the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome undergoing IVF compared with the long agonist protocol. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI Conference Proceedings. Primary outcome was OHSS incidence. Secondary outcomes were total duration and dose of gonadotrophin, number of oocytes retrieved and clinical pregnancy and miscarriage rates. A total of 966 women were included in nine randomized controlled trials. There was inconsistency in definition, classification of severity and reporting of the OHSS rate. There was no difference in the incidence of severe OHSS in the antagonist group compared with the long agonist group (relative risk 0.61; 95% CI 0.23 to 1.64). However, when all moderate and severe OHSS cases were pooled, the antagonist protocol was associated with significantly lower risk of OHSS (relative risk 0.60; 95% CI 0.48-0.76; P

A systematic review of studies evaluating the influence of outpatient (office) hysteroscopy on the outcome of the subsequent IVF cycle was conducted. MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI Conference Proceedings, ISRCTN Register and Meta-register were searched for randomized controlled trials (up to July 2007). All trials comparing the outcome of IVF treatment performed in patients who had outpatient hysteroscopy in the cycle preceding their IVF treatment with a control group in which hysteroscopy was not performed were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Study authors were contacted for additional information. The main outcome measure was pregnancy rate. In total, 1691 participants were included in two randomized (n = 941) and three non-randomized controlled studies (n = 750). The quality of the studies was variable. Meta-analyses of the results of five studies showed evidence of benefit from outpatient hysteroscopy in improving the pregnancy rate in the subsequent IVF cycle (pooled relative risk = 1.75, 95% CI 1.51-2.03). The evidence from randomized trials was consistent with that from non-randomized controlled studies. Future robust randomized trials comparing outpatient hysteroscopy or mini-hysteroscopy with no intervention before IVF treatment would be a useful addition to further guide clinical practice.

Many randomized trials have evaluated the use of various pituitary suppression regimens to improve outcome of poor responders undergoing IVF treatment. A systematic review was conducted of the trials of gonadotrophin-releasing hormone (GnRH) agonist long regimen, GnRH agonist short regimen, GnRH antagonist regimen, as well as other pituitary suppression regimens in poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. The search included MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI proceedings, and all randomized controlled trials comparing the various pituitary suppression regimens in poor responders were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measures were number of oocytes retrieved, cycles cancelled before oocyte retrieval and pregnancy rates. A total of 680 women considered as poor responders undergoing IVF/ICSI treatment were included in nine randomized controlled trials. The quality of these studies was variable: for example, only three of the studies had clear evidence of allocation concealment. Meta-analyses of the results of the studies did not show a consistent benefit for any one pituitary suppression regimen over the other regimens in improving outcome measures. Currently available evidence does not favour any one pituitary suppression regimen for women with poor ovarian response undergoing IVF/ICSI treatment.