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The Cochrane Database of Systematic... May 2016Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction.
OBJECTIVES
To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using GRADE methods.
MAIN RESULTS
Twelve RCTs investigated the effect of intrauterine administration of hCG for 4038 subfertile women undergoing assisted reproduction. The intra-cavity hCG (IC-hCG) was administered in variable doses at different timings before the ET. The source of hCG was from the urine of pregnant women or from cell cultures using recombinant DNA technology.Most of the studies (9/12) were at high risk of bias in at least one of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.For the analyses of live birth and clinical pregnancy, there was considerable heterogeneity (I(2) greater than 75%) and we did not undertake a meta-analysis. Exploration for the sources of heterogeneity identified two key pre-specified variables as important determinants: stage of ET (cleavage versus blastocyst stage) and dose of IC-hCG (less than 500 international units (IU) versus 500 IU or greater). We then performed meta-analysis for these analyses within the subgroups defined by stage of embryo and dose of IC-hCG.There was an increase in live birth rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (risk ratio (RR) 1.57, 95% confidence interval (CI) 1.32 to 1.87, three RCTs, n = 914, I(2) = 0%, moderate quality evidence). In a clinic with a live birth rate of 25% per cycle then the use of IC-hCG -500 IU or greater would be associated with a live birth rate that varies from 33% to 46%. We did not observe a significant effect on live birth in any of the other subgroups.The was an increase in clinical pregnancy rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (RR 1.41, 95% CI 1.25 to 1.58, seven RCTs, n = 1414, I(2) = 0%, moderate quality evidence). We did not observe a significant effect on clinical pregnancy in either of the other subgroups.There was no evidence that miscarriage was influenced by intrauterine hCG administration (RR 1.09, 95% CI 0.83 to 1.43, seven RCTs, n = 3395, I(2) = 0%, very low quality evidence).Other complications reported in the included studies were ectopic pregnancy (three RCTs, n = 915, three events overall), heterotopic pregnancy (one RCT, n = 495, one event), intrauterine death (two RCTs, n = 978, 21 events) and triplets (one RCT, n = 48, three events). There was no evidence of a difference between the groups, but there were too few events to allow any conclusions to be drawn and the evidence was very low quality.
AUTHORS' CONCLUSIONS
The pregnancy outcome for cleavage-stage ETs using an IC-hCG dose of 500 IU or greater is promising. However, given the small size and the variable quality of the trials and the fact that the positive finding was from a subgroup analysis, the current evidence for IC-hCG treatment does not support its use in assisted reproduction cycles. A definitive large clinical trial with live birth as the primary outcome is recommended. There was no evidence that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo stage at transfer or dose of IC-hCG. There were too few events to allow any conclusions to be drawn with regard to other complications.
Topics: Abortion, Spontaneous; Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Humans; Infertility, Female; Live Birth; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Uterus
PubMed: 27195724
DOI: 10.1002/14651858.CD011537.pub2 -
The Cochrane Database of Systematic... Dec 2014In many countries intrauterine insemination (IUI) is the treatment of first choice for a subfertile couple when the infertility work up reveals an ovulatory cycle, at... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In many countries intrauterine insemination (IUI) is the treatment of first choice for a subfertile couple when the infertility work up reveals an ovulatory cycle, at least one open Fallopian tube and sufficient spermatozoa. The final goal of this treatment is to achieve a pregnancy and deliver a healthy (singleton) live birth. The probability of conceiving with IUI depends on various factors including age of the couple, type of subfertility, ovarian stimulation and the timing of insemination. IUI should logically be performed around the moment of ovulation. Since spermatozoa and oocytes have only limited survival time correct timing of the insemination is essential. As it is not known which technique of timing for IUI results in the best treatment outcome, we compared different techniques for timing IUI and different time intervals.
OBJECTIVES
To evaluate the effectiveness of different synchronisation methods in natural and stimulated cycles for IUI in subfertile couples.
SEARCH METHODS
We searched for all publications which described randomised controlled trials of the timing of IUI. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (1966 to October 2014), EMBASE (1974 to October 2014), MEDLINE (1966 to October 2014) and PsycINFO (inception to October 2014) electronic databases and prospective trial registers. Furthermore, we checked the reference lists of all obtained studies and performed a handsearch of conference abstracts.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing different timing methods for IUI were included. The following interventions were evaluated: detection of luteinising hormone (LH) in urine or blood, single test; human chorionic gonadotropin (hCG) administration; combination of LH detection and hCG administration; basal body temperature chart; ultrasound detection of ovulation; gonadotropin-releasing hormone (GnRH) agonist administration; or other timing methods.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the trials, extracted the data and assessed study risk of bias. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
Eighteen RCTs were included in the review, of which 14 were included in the meta-analyses (in total 2279 couples). The evidence was current to October 2013. The quality of the evidence was low or very low for most comparisons . The main limitations in the evidence were failure to describe study methods, serious imprecision and attrition bias.Ten RCTs compared different methods of timing for IUI. We found no evidence of a difference in live birth rates between hCG injection versus LH surge (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.06 to 18, 1 RCT, 24 women, very low quality evidence), urinary hCG versus recombinant hCG (OR 1.17, 95% CI 0.68 to 2.03, 1 RCT, 284 women, low quality evidence) or hCG versus GnRH agonist (OR 1.04, 95% CI 0.42 to 2.6, 3 RCTS, 104 women, I(2) = 0%, low quality evidence).Two RCTs compared the optimum time interval from hCG injection to IUI, comparing different time frames that ranged from 24 hours to 48 hours. Only one of these studies reported live birth rates, and found no difference between the groups (OR 0.52, 95% CI 0.27 to 1.00, 1 RCT, 204 couples). One study compared early versus late hCG administration and one study compared different dosages of hCG, but neither reported the primary outcome of live birth.We found no evidence of a difference between any of the groups in rates of pregnancy or adverse events (multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS)). However, most of these data were very low quality.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine whether there is any difference in safety and effectiveness between different methods of synchronization of ovulation and insemination. More research is needed.
Topics: Adult; Body Temperature; Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Insemination, Artificial; Luteinizing Hormone; Male; Ovulation Detection; Randomized Controlled Trials as Topic; Time Factors; Young Adult
PubMed: 25528596
DOI: 10.1002/14651858.CD006942.pub3 -
The Cochrane Database of Systematic... 2003Laboratory evidence in the 1940s demonstrated a positive role of placental hormones in the continuation of pregnancy. It was suggested that diethylstilbestrol was the... (Review)
Review
BACKGROUND
Laboratory evidence in the 1940s demonstrated a positive role of placental hormones in the continuation of pregnancy. It was suggested that diethylstilbestrol was the oestrogen of choice for prevention of miscarriages. Observational studies were carried out with apparently positive results, on which clinical practice was based. This led to a worldwide usage of diethylstilbestrol despite controlled studies with contrary findings.
OBJECTIVES
To determine the effects of antenatal administration of oestrogens, mainly diethylstilbestrol, on high risk and unselected pregnancy as regards miscarriages and other outcomes.
SEARCH STRATEGY
We searched the Pregnancy and Childbirth Group Specialised Register of controlled trials in November 2002.
SELECTION CRITERIA
Randomised and quasi-randomised trials were included.
DATA COLLECTION AND ANALYSIS
Both reviewers extracted data from the studies identified that met the selection criteria, and the data were analysed using the RevMan software.
MAIN RESULTS
Miscarriage, preterm labour, low birthweight and stillbirth or neonatal death were not positively influenced by the intervention (diethylstilbestrol) as compared to the control group. Diethylstilbestrol in utero exposure led to increased rate of miscarriage and preterm birth. There was also an increase in the numbers of babies weighing less than 2500 grams. The maternal outcome in terms of pre-eclampsia was not influenced. Exposed female offsprings have a non-significant trend towards more cancer of the genital tract and cancer other than of the genital tract. Primary infertility, adenosis of the vagina/cervix in female offsprings, and testicular abnormality in male offsprings were significantly higher in those exposed to diethylstilbestrol before birth.
REVIEWER'S CONCLUSIONS
There was no benefit with the use of diethylstilbestrol in preventing miscarriages. Both short and long-term adverse outcomes in exposed offsprings were demonstration of the harm that this intervention caused women and their offspring during its usage.
Topics: Abortion, Spontaneous; Diethylstilbestrol; Estrogens, Non-Steroidal; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome
PubMed: 12918007
DOI: 10.1002/14651858.CD004353 -
BMC Endocrine Disorders Nov 2018After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility.
METHODS
To determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials. Clinical trials were systematically searched in Medline, Embase, and the Cochrane central register of controlled trials databases. The keywords and major terms covered "hypogonadotropic hypogonadism", "kallmann syndrome", "assisted reproductive techniques", "intrauterine insemination", "intracytoplasmic sperm injection", "testicular sperm extraction", "in vitro fertilization", "embryo transplantation" and "intra-Fallopian transfer".
RESULTS
A total of 388 pregnancies occurred among 709 CHH patients who received ART (effectiveness 46, 95% confidence interval 0.39 to 0.53) in the 20 studies we included. The I in trials assessing overall pregnancy rate (PR) per embryo transfer (ET) cycle was 73.06%. Similar results were observed in subgroup analysis by different gender. Regression indicates pregnancy rate decreases with increasing age. Fertilization, implantation and live birth rates (72, 36 and 40%) showed no significant differences as compared to infertility due to other causes.
CONCLUSIONS
Despite CHH patients usually being difficult to generate gametes, their actual chances of fertility are similar to subjects with other non-obstructive infertility. ART is a suitable option for CHH patients who do not conceive after long-term gonadotropin treatment.
Topics: Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility; Male; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted
PubMed: 30453944
DOI: 10.1186/s12902-018-0313-8 -
Frontiers in Neuroscience 2021The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before...
The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. In particular, several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal, and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors-i.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure-may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor.
PubMed: 34616274
DOI: 10.3389/fnins.2021.721605 -
Journal of Translational Medicine Mar 2021This study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotropin (free...
Second trimester maternal serum D-dimer combined with alpha-fetoprotein and free β-subunit of human chorionic gonadotropin predict hypertensive disorders of pregnancy: a systematic review and retrospective case-control study.
BACKGROUND
This study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotropin (free β-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP).
MATERIALS AND METHODS
In this retrospective case-control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free β-hCG levels for HDP.
RESULTS
DD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free β-hCG > DD > DD + AFP > DD + free β-hCG > AFP + free β-hCG > AFP > free β-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free β-hCG alone and AFP + free β-hCG could reduce false positive rate and improve + LR.
CONCLUSION
DD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free β-hCG + AFP had the greatest diagnostic value for SPE.
Topics: Biomarkers; Case-Control Studies; Chorionic Gonadotropin; Female; Fibrin Fibrinogen Degradation Products; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Retrospective Studies; alpha-Fetoproteins
PubMed: 33653375
DOI: 10.1186/s12967-021-02718-4 -
The Cochrane Database of Systematic... 2004The aspiration of the granulosa cells that surround the oocyte and the use of gonadotropin releasing hormone agonists (GnRHa) during assisted reproduction technology... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aspiration of the granulosa cells that surround the oocyte and the use of gonadotropin releasing hormone agonists (GnRHa) during assisted reproduction technology (ART) treatment can interfere with the production, during the luteal phase, of progesterone, which is necessary for successful implantation of the embryo. Providing hormonal supplementation during the luteal phase with either progesterone itself, or human chorionic gonadotropin (hCG), which stimulates progesterone production, may improve implantation and, thus, pregnancy rates.
OBJECTIVES
To determine (1) if luteal phase support after assisted reproduction increases the pregnancy rate, (2) the optimal hormone for luteal phase support, i.e. hCG, progesterone, or a combination of both, and (3) the optimal route of progesterone administration.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1971 to Dec 2003), EMBASE (1985 to Dec 2003). We handsearched reference lists of relevant articles were scanned, and abstract books from scientific meetings up to December 2003.
SELECTION CRITERIA
Randomized controlled trials of luteal phase support after ART treatment, comparing hCG or progesterone with placebo or no treatment, comparing progesterone with hCG, progesterone plus hCG, or progesterone plus estrogen, or comparing different routes of progesterone administration. Quasi-randomized trials were excluded from the main analyses, but included in a secondary analysis for each comparison.
DATA COLLECTION AND ANALYSIS
For each comparison, data on live birth, ongoing and clinical pregnancy per embryo or gamete transfer procedure, miscarriage per clinical pregnancy, ovarian hyperstimulation syndrome (OHSS) per transfer, and multiple pregnancy per clinical pregnancy were extracted into 2 x 2 tables and subgrouped by use of GnRHa in the ovarian stimulation regimen. The odds ratio (OR) and risk difference (RD) were calculated.
MAIN RESULTS
Fifty-nine studies were included in the review. Luteal phase support with hCG provided significant benefit, compared to placebo or no treatment, in terms of increased ongoing pregnancy rates (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.32 to 4.29) and decreased miscarriage rates (OR 0.12, 95% CI 0.03 to 0.50), but only when GnRHa was used. The odds of OHSS increased 20-fold when hCG was used in cycles with GnRHa. Progesterone use resulted in a small but significant increase in pregnancy rates (OR 1.34, 95% CI 1.01 to 1.79) when trials with and without GnRHa were grouped together, but no effect on the miscarriage rate was observed. No significant difference was found between progesterone and hCG or between progesterone and progesterone plus hCG or estrogen in terms of pregnancy or miscarriage rates, but the odds of OHSS were more than 2-fold higher with treatments involving hCG than with progesterone alone(OR 3.06, 95% CI 1.59 to 5.86). Comparing routes of progesterone administration, reductions in clinical pregnancy rate with the oral route, compared to the intramuscular or vaginal routes, did not reach statistical significance, but there was evidence of benefit of the intramuscular over the vaginal route for the outcomes of ongoing pregnancy and live birth. No significant difference in pregnancy rate was observed between vaginal progesterone gel and other types of vaginal progesterone.
REVIEWERS' CONCLUSIONS
Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rate. hCG does not provide better results than progesterone, and is associated with a greater risk of OHSS when used with GnRHa. The optimal route of progesterone administration has not yet been established.
Topics: Chorionic Gonadotropin; Female; Humans; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone; Reproductive Techniques, Assisted
PubMed: 15266541
DOI: 10.1002/14651858.CD004830 -
BMC Complementary and Alternative... Nov 2013Traditional Chinese medicine has been widely used for the treatment of recurrent miscarriage in China and other Asian countries for long time. We conducted this review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traditional Chinese medicine has been widely used for the treatment of recurrent miscarriage in China and other Asian countries for long time. We conducted this review to systematically summarize the evidences of Chinese herbal medicine (CHM) for the prevention and treatment of recurrent miscarriage in randomized trials, and evaluate the effectiveness and safety of CHM compared with placebo or conventional medicine.
METHODS
We searched studies in PubMed, ClinicalTrials, the Cochrane Library, CNKI, SinoMed and VIP databases until December, 2012. Randomized trials on CHM alone or in combination with conventional medicine for recurrent miscarriage compared with placebo or conventional medicine were included. We evaluated the methodological quality of each included trials using the Cochrane risk of bias tool.
RESULTS
A total of 41 RCTs (3660 participants) were included. The majority of trials had a high or unclear risk of bias. CHM used alone or plus progesterone-based treatment showed superior effect over progesterone-based treatment in improving live birth rate and embryonic developmental state (measured by B ultrasound). However, there is substantial heterogeneity within each subgroup analysis (I2 ranging from 35% to 71%). CHM plus progesterone and hCG-based treatment was superior to progesterone and hCG-based treatment in improving the embryonic developmental state, but not live birth rate. No severe adverse events were reported in relation to CHM.
CONCLUSIONS
Some Chinese herbal medicines or in combination with progesterone-based treatment demonstrated potentially beneficial effect in improving live birth rate and embryonic developmental state for women with recurrent miscarriage. However, due to the substantial heterogeneity among the herbal interventions and limitations of methodological quality of the included trials, it is not possible to recommend any specific CHMs for recurrent miscarriage. Further rigorous clinical trials are warranted to evaluate the efficacy and safety of CHM.
Topics: Abortion, Habitual; Chorionic Gonadotropin; Drugs, Chinese Herbal; Female; Humans; Live Birth; Placebos; Pregnancy; Progesterone; Randomized Controlled Trials as Topic; Reproductive Control Agents
PubMed: 24245671
DOI: 10.1186/1472-6882-13-320 -
The Cochrane Database of Systematic... Oct 2014Human chorionic gonadotropin (HCG) is routinely used for final oocyte maturation triggering in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human chorionic gonadotropin (HCG) is routinely used for final oocyte maturation triggering in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles, but the use of HCG for this purpose may have drawbacks. Gonadotropin-releasing hormone (GnRH) agonists present an alternative to HCG in controlled ovarian hyperstimulation (COH) treatment regimens in which the cycle has been down-regulated with a GnRH antagonist. This is an update of a review first published in 2010.
OBJECTIVES
To evaluate the effectiveness and safety of GnRH agonists in comparison with HCG for triggering final oocyte maturation in IVF and ICSI for women undergoing COH in a GnRH antagonist protocol.
SEARCH METHODS
We searched databases including the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of Controlled Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and trial registers for published and unpublished articles (in any language) on randomised controlled trials (RCTs) of gonadotropin-releasing hormone agonists versus HCG for oocyte triggering in GnRH antagonist IVF/ICSI treatment cycles. The search is current to 8 September 2014.
SELECTION CRITERIA
RCTs that compared the clinical outcomes of GnRH agonist triggers versus HCG for final oocyte maturation triggering in women undergoing GnRH antagonist IVF/ICSI treatment cycles were included.
DATA COLLECTION AND ANALYSIS
Two or more review authors independently selected studies, extracted data and assessed study risk of bias. Treatment effects were summarised using a fixed-effect model, and subgroup analyses were conducted to explore potential sources of heterogeneity. Treatment effects were expressed as mean differences (MDs) for continuous outcomes and as odds ratios (ORs) for dichotomous outcomes, together with 95% confidence intervals (CIs). Primary outcomes were live birth and rate of ovarian hyperstimulation syndrome (OHSS) per women randomised. Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods were used to assess the quality of the evidence for each comparison.
MAIN RESULTS
We included 17 RCTs (n = 1847), of which 13 studies assessed fresh autologous cycles and four studies assessed donor-recipient cycles. In fresh autologous cycles, GnRH agonists were associated with a lower live birth rate than was seen with HCG (OR 0.47, 95% CI 0.31 to 0.70; five RCTs, 532 women, I(2) = 56%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving live birth with the use of HCG, the chance of a live birth with the use of an GnRH agonist would be between 12% and 24%.In women undergoing fresh autologous cycles, GnRH agonists were associated with a lower incidence of mild, moderate or severe OHSS than was HCG (OR 0.15, 95% CI 0.05 to 0.47; eight RCTs, 989 women, I² = 42%, moderate-quality evidence). This suggests that for a woman with a 5% risk of mild, moderate or severe OHSS with the use of HCG, the risk of OHSS with the use of a GnRH agonist would be between nil and 2%.In women undergoing fresh autologous cycles, GnRH agonists were associated with a lower ongoing pregnancy rate than was seen with HCG (OR 0.70, 95% CI 0.54 to 0.91; 11 studies, 1198 women, I(2) = 59%, low-quality evidence) and a higher early miscarriage rate (OR 1.74, 95% CI 1.10 to 2.75; 11 RCTs, 1198 women, I² = 1%, moderate-quality evidence). However, the effect was dependent on the type of luteal phase support provided (with or without luteinising hormone (LH) activity); the higher rate of pregnancies in the HCG group applied only to the group that received luteal phase support without LH activity (OR 0.36, 95% CI 0.21 to 0.62; I(2) = 73%, five RCTs, 370 women). No evidence was found of a difference between groups in risk of multiple pregnancy (OR 3.00, 95% CI 0.30 to 30.47; two RCTs, 62 women, I(2) = 0%, low-quality evidence).In women with donor-recipient cycles, no evidence suggested a difference between groups in live birth rate (OR 0.92, 95% CI 0.53 to 1.61; one RCT, 212 women) or ongoing pregnancy rate (OR 0.88, 95% CI 0.58 to 1.32; three RCTs, 372 women, I² = 0%). We found evidence of a lower incidence of OHSS in the GnRH agonist group than in the HCG group (OR 0.05, 95% CI 0.01 to 0.28; three RCTs, 374 women, I² = 0%).The main limitation in the quality of the evidence was risk of bias associated with poor reporting of methods in the included studies.
AUTHORS' CONCLUSIONS
Final oocyte maturation triggering with GnRH agonist instead of HCG in fresh autologous GnRH antagonist IVF/ICSI treatment cycles prevents OHSS to the detriment of the live birth rate. In donor-recipient cycles, use of GnRH agonists instead of HCG resulted in a lower incidence of OHSS, with no evidence of a difference in live birth rate.Evidence suggests that GnRH agonist as a final oocyte maturation trigger in fresh autologous cycles is associated with a lower live birth rate, a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) and a higher rate of early miscarriage (less than 12 weeks). GnRH agonist as an oocyte maturation trigger could be useful for women who choose to avoid fresh transfers (for whatever reason), women who donate oocytes to recipients or women who wish to freeze their eggs for later use in the context of fertility preservation.
Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Oocyte Donation; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 25358904
DOI: 10.1002/14651858.CD008046.pub4 -
Reproductive Biomedicine Online Jul 2009There is an ongoing debate over the optimal dose of urinary HCG (u-HCG) that can trigger final oocyte maturation, leading to higher IVF success rate without increasing... (Review)
Review
There is an ongoing debate over the optimal dose of urinary HCG (u-HCG) that can trigger final oocyte maturation, leading to higher IVF success rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS). A systematic review was conducted of all studies that compared the effect of at least two doses of u-HCG for final oocyte maturation on IVF outcomes and on the incidence of OHSS. The primary outcome was the live birth rate, and the secondary end-points were the number of oocytes retrieved, fertilization, implantation and pregnancy rates, and the incidence of OHSS. Only two amongst the six included studies were randomized controlled trials (RCT). Meta-analytic pool was not feasible due to insufficient number of studies assessing the same outcome and significant heterogeneity. The majority of studies concluded that the clinical outcomes were similar between women receiving 5000 or 10,000 IU of u-HCG. The incidence of OHSS was not reduced in the high-risk population even with lower dose of u-HCG. Until large scale RCT addressing the clinical effectiveness and the adverse outcomes related to various doses of u-HCG are conducted, the dose of u-HCG for final oocyte maturation for women referred for IVF needs to be individualized.
Topics: Birth Rate; Chorionic Gonadotropin; Female; Fertilization in Vitro; Humans; Oocytes; Ovulation Induction; Pregnancy
PubMed: 19573290
DOI: 10.1016/s1472-6483(10)60045-4