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The Cochrane Database of Systematic... Feb 2011hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET). (Review)
Review
BACKGROUND
hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET).
OBJECTIVES
To compare the effectiveness of hMG with rFSH in ovarian stimulation protocols in IVF or ICSI treatment cycles.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 3rd Jan 2002), PubMed, MEDLINE, Web of Science (all searched 1985 to May 15 2002), and reference lists of articles. We also contacted manufacturers and researchers in the field.
SELECTION CRITERIA
Randomised trials comparing hMG with rFSH for ovarian stimulation in IVF or ICSI treatment for treatment of infertility in normogonadotrophic women.
DATA COLLECTION AND ANALYSIS
The main outcome measure was ongoing pregnancy/live birth per woman.Secondary outcomes included total gonadotrophin dose used, cancellation, number of oocytes retrieved, implantation, clinical pregnancy per woman, multiple pregnancy, spontaneous abortion and ovarian hyperstimulation syndrome. Peto odds ratios (OR) for hMG relative to rFSH were calculated after testing for homogeneity of treatment effect across all trials. Analyses were performed separately for the three different GnRHa protocols used: (1) without GnRHa down-regulation, (2) with GnRHa down-regulation using a short protocol and (3) with GnRHa down-regulation using a long protocol.
MAIN RESULTS
Eight trials that met the inclusion criteria could be identified. One trial did not use down-regulation, one trial used a short protocol and six trials used a long down-regulation protocol. In the one trial with non-down-regulated women and in the one trial that used a short down-regulation protocol there was no evidence of a difference between hMG and rFSH in any clinical outcome. Data of four truly randomised trials in women down-regulated using a long protocol could be pooled. There was no evidence of a difference between hMG and rFSH in ongoing pregnancy/live birth per woman (OR 1.27; 95% CI 0.98 to 1.64). Furthermore there was no clear difference on any of the secondary outcomes, although the clinical pregnancy rate per woman was of borderline significance in favour of hMG (summary OR 1.28; 95% CI 1.00 to 1.64). The other secondary outcomes were comparable for both gonadotrophins.
AUTHORS' CONCLUSIONS
For all three GnRHa protocols analysed there is insufficient evidence of a difference between hMG and rFSH on ongoing pregnancy or live birth. More large randomised trials are needed to estimate the difference between hMG and rFSH more precisely. Such trials should preferably (1) use a consistent long GnRHa protocol and (2) use a fixed dose of gonadotrophin such to prevent potentially subjective decisions of the clinician in dosing and (3) take live birth as primary endpoint. At this moment in time however, in prescribing gonadotrophins for ovarian hyperstimulation in IVF one should use the least expensive medication.
Topics: Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gamete Intrafallopian Transfer; Humans; Menotropins; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 21328264
DOI: 10.1002/14651858.CD003973.pub2 -
The Cochrane Database of Systematic... 2000To conduct a systematic overview of available data comparing FSH and hMG in IVF treatment cycles. (Review)
Review
OBJECTIVES
To conduct a systematic overview of available data comparing FSH and hMG in IVF treatment cycles.
SEARCH STRATEGY
This review has drawn on the search strategy developed for the Subfertility Group as a whole. Relevant trials were identified in the Group's Specialised Register of Controlled Trials. See Review Group details for more information.
DATA COLLECTION AND ANALYSIS
A systematic review and meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Common odds ratios (OR) were calculated after demonstrating homogeneity of treatment effect across all trials.
MAIN OUTCOME MEASURES
Clinical pregnancy rates per cycle started, per cycle reaching oocyte retrieval, and per cycle reaching embryo transfer (ET).
RESULTS
Eight trials met the inclusion criteria. The overall OR in favour of FSH for cycle start, oocyte retrieval, and ET were 1.70 (95% CI, 1.11-2.60), 1.68 (95% CI, 1.10-2.56), and 1.69 (95% CI, 1.10-2.59), respectively.
REVIEWER'S CONCLUSIONS
This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.
Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Ovulation Induction; Pregnancy
PubMed: 10796481
DOI: 10.1002/14651858.CD000061 -
The Cochrane Database of Systematic... 2000The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in women with clomiphene resistance WHO group 2 dysfunction undergoing... (Review)
Review
BACKGROUND
The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in women with clomiphene resistance WHO group 2 dysfunction undergoing ovulation induction as well as the risk of spontaneous abortion if conception takes place. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotropin (hMG). Ovulation induction in women with clomiphene resistant WHO group 2 dysfunction who often have clinical features of polycystic ovarian syndrome (PCOS), is a major challenge. The risks of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are increased in this population. There also appears to be an increased risk of spontaneous abortion in those who conceive, perhaps associated with elevated LH levels. Semi-purified preparations of FSH have been developed in an effort to reduce the impact of exogenous LH, relatively high levels of which are present in human menopausal gonadotrophins.
OBJECTIVES
To determine the effectiveness of daily FSH versus daily hMG in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of rates of pregnancy and moderate to severe ovarian hyperstimulation syndrome (OHSS).
SEARCH STRATEGY
The Cochrane Subfertility Review Group specialised register of controlled trials was searched.
SELECTION CRITERIA
All RCTs relevant to the clinical question were selected.
DATA COLLECTION AND ANALYSIS
A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.
DATA SYNTHESIS
2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2.
MAIN RESULTS
No significant benefit was demonstrated from semi-purified FSH versus hMG in terms of pregnancy rate: common odds ratio per patient 0.66 (95% CI 0.35-1.24) and per cycle 0.89 (95% CI 0.51-1.53). FSH appeared to be associated with a reduction in moderate to severe OHSS: common odds ratios 0.2 (95% CI 0.09-0.46).
REVIEWER'S CONCLUSIONS
In women with PCOS, no significant difference could be demonstrated between FSH and hMG, in terms of pregnancy rate. However, given similar cost, potential advantages in terms of purity and a possible reduction in OHSS risk, highly purified or recombinant FSH are likely to be widely adopted in the future. Further research should consider live birth as a primary clinical outcome, given concerns over the association between high androgen and LH levels with spontaneous abortion risk.
Topics: Clomiphene; Estrogen Antagonists; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy
PubMed: 10796690
DOI: 10.1002/14651858.CD000087 -
Journal of Endocrinological... May 2015Gonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There... (Review)
Review
Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation.
BACKGROUND
Gonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There is still a lively debate on which type of gonadotropin medication should be used, either human menopausal gonadotropin or recombinant follicle-stimulating hormone. The objective of the study was to perform a systematic review of the recent literature to compare recombinant follicle-stimulating hormone to human menopausal gonadotropin with the aim to assess any differences in terms of efficacy and to provide a cost evaluation based on findings of this systematic review.
METHODS
The review was conducted selecting prospective, randomized, controlled trials comparing the two gonadotropin medications from a literature search of several databases. The outcome measure used to evaluate efficacy was the number of oocytes retrieved per cycle. In addition, a cost evaluation was performed based on retrieved efficacy data.
RESULTS
The number of oocytes retrieved appeared to be higher for human menopausal gonadotropin in only 2 studies while 10 out of 13 studies showed a higher mean number of oocytes retrieved per cycle for recombinant follicle-stimulating hormone. The results of the cost evaluation provided a similar cost per oocyte for both hormones.
CONCLUSIONS
Recombinant follicle-stimulating hormone treatment resulted in a higher oocytes yield per cycle than human menopausal gonadotropin at similar cost per oocyte.
Topics: Female; Follicle Stimulating Hormone, Human; Humans; Menotropins; Outcome Assessment, Health Care; Ovulation Induction
PubMed: 25480425
DOI: 10.1007/s40618-014-0204-4 -
The Cochrane Database of Systematic... Apr 1996Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin... (Review)
Review
BACKGROUND
Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin releasing hormone analogue (GnRHa) used prior to human menopausal gonadotropin (hMG/FSH) administration may improve the outcome of ovulation induction.
OBJECTIVES
To assess if GnRHa pre-treatment plus FSH/hMG increase the rate of clinical pregnancy and/or decrease the rate of spontaneous abortion in women with WHO group two ovulatory dysfunction, compared with hMG/FSH alone.
SEARCH STRATEGY
The Cochrane Subfertility Review Group specialised register of controlled trials was searched.
SELECTION CRITERIA
All relevant published and unpublished RCTs were selected. Three RCTs were identified comparing these two approaches.
DATA EXTRACTION
A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.
DATA SYNTHESIS
Two by two tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using by two.
MAIN RESULTS
Studies were clinically and statistically homogenous. Common odds ratios for pregnancy per treatment cycle and moderate to severe ovarian hyperstimulation syndrome (OHSS) were 1.50 (0.72-3.12) and 1.40 (0.5-3.92) respectively.
AUTHORS' CONCLUSIONS
These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.
Topics: Clomiphene; Drug Resistance; Drug Therapy, Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Menotropins; Polycystic Ovary Syndrome
PubMed: 17636588
DOI: 10.1002/14651858.CD000097.pub2 -
The Cochrane Database of Systematic... Jan 2019Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate.
OBJECTIVES
To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS), and women who do not ovulate or conceive after clomiphene citrate.
SEARCH METHODS
In January 2018, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, the World Health Organisation clinical trials register, Clinicaltrials.gov, LILACs, and PubMed databases, and Google Scholar. We checked references of in all obtained studies. We had no language restrictions.
SELECTION CRITERIA
All randomised controlled trials reporting data on clinical outcomes in women with PCOS who did not ovulate or conceive on clomiphene citrate, and undergoing ovulation induction with urinary-derived gonadotrophins, including urofollitropin (uFSH) in purified FSH (FSH-P) or highly purified FSH (FSH-HP) form, human menopausal gonadotropin (HMG) and highly purified human menopausal gonadotrophin (HP-HMG), or recombinant FSH (rFSH), or continuing clomiphene citrate. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that described co-treatment with clomiphene citrate, metformin, luteinizing hormone, or letrozole.
DATA COLLECTION AND ANALYSIS
Three review authors (NW, EK, and MvW) independently selected studies for inclusion, assessed risk of bias, and extracted study data. Primary outcomes were live birth rate per woman and multiple pregnancy per woman. Secondary outcomes were clinical pregnancy, miscarriage, incidence of ovarian hyperstimulation syndrome (OHSS) per woman, total gonadotrophin dose, and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the risk ratio (RR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria.
MAIN RESULTS
The review included 15 trials with 2387 women. Ten trials compared rFSH with urinary-derived gonadotrophins (three compared rFSH with human menopausal gonadotrophin, and seven compared rFSH with FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P. One trial compared FSH with continued clomiphene citrate.Recombinant FSH (rFSH) versus urinary-derived gonadotrophinsThere may be little or no difference in the birth rate between rFSH and urinary-derived gonadotrophins (RR 1.21, 95% confidence interval (CI) 0.83 to 1.78; five trials, N = 505; I² = 9%; low-quality evidence). This suggests that for the observed average live birth per woman who used urinary-derived FSH of 16%, the chance of live birth with rFSH is between 13% and 28%. There may also be little or no difference between groups in incidence of multiple pregnancy (RR 0.86, 95% CI 0.46 to 1.61; eight trials, N = 1368; I² = 0%; low-quality evidence), clinical pregnancy rate (RR 1.05, 95% CI 0.88 to 1.27; eight trials, N = 1330; I² = 0; low-quality evidence), or miscarriage rate (RR 1.20, 95% CI 0.71 to 2.04; seven trials, N = 970; I² = 0; low-quality evidence). We are uncertain whether rFSH reduces the incidence of OHSS (RR 1.48, 95% CI 0.82 to 2.65, ten trials, n=1565, I² = 0%, very low-quality evidence).Human menopausal gonadotrophin (HMG) or HP-HMG versus uFSHWhen compared to uFSH, we are uncertain whether HMG or HP-HMG improves live birth rate (RR 1.28, 95% CI 0.65 to 2.52; three trials, N = 138; I² = 0%; very low quality evidence), or reduces multiple pregnancy rate (RR 2.13, 95% CI 0.51 to 8.91; four trials, N = 161; I² = 0%; very low quality evidence). We are also uncertain whether HMG or HP-HMG improves clinical pregnancy rate (RR 1.31, 95% CI 0.66 to 2.59; three trials, N = 102; I² = 0; very low quality evidence), reduces miscarriage rate (RR 0.33, 95% CI 0.06 to 1.97; two trials, N = 98; I² = 0%; very low quality evidence), or reduces the incidence of OHSS (RR 7.07, 95% CI 0.42 to 117.81; two trials, N = 53; very low quality evidence) when compared to uFSH.Gonadotrophins versus continued clomiphene citrateGonadotrophins resulted in more live births than continued clomiphene citrate (RR 1.24, 95% CI 1.05 to 1.46; one trial, N = 661; I² = 0%; moderate-quality evidence). This suggests that for a woman with a live birth rate of 41% with continued clomiphene citrate, the live birth rate with FSH was between 43% and 60%. There is probably little or no difference in the incidence of multiple pregnancy between treatments (RR 0.89, 95% CI 0.33 to 2.44; one trial, N = 661; I² = 0%; moderate-quality evidence). Gonadotrophins resulted in more clinical pregnancies than continued clomiphene citrate (RR 1.31, 95% CI 1.13 to 1.52; one trial, N = 661; I² = 0%; moderate-quality evidence), and more miscarriages (RR 2.23, 95% CI 1.11 to 4.47; one trial, N = 661; I² = 0%; moderate-quality evidence). None of the women developed OHSS.
AUTHORS' CONCLUSIONS
There may be little or no difference in live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate between urinary-derived gonadotrophins and recombinant follicle stimulating hormone in women with polycystic ovary syndrome. For human menopausal gonadotropin or highly purified human menopausal gonadotrophin versus urinary follicle stimulating hormone we are uncertain whether one or the other improves or lowers live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate. We are uncertain whether any of the interventions reduce the incidence of ovarian hyperstimulation syndrome. We suggest weighing costs and convenience in the decision to use one or the other gonadotrophin. In women with clomiphene citrate failure, gonadotrophins resulted in more live births than continued clomiphene citrate without increasing multiple pregnancies.
Topics: Abortion, Spontaneous; Birth Rate; Clomiphene; Drug Resistance; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Live Birth; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Randomized Controlled Trials as Topic
PubMed: 30648738
DOI: 10.1002/14651858.CD010290.pub3 -
Fertility and Sterility Apr 2002To determine the relative efficacy of recombinant FSH (rFSH) and urinary FSH (uFSH) for ovarian stimulation in assisted reproductive techniques (ART). (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To determine the relative efficacy of recombinant FSH (rFSH) and urinary FSH (uFSH) for ovarian stimulation in assisted reproductive techniques (ART).
DESIGN
Systematic review and meta-analysis of randomized, controlled trials comparing rFSH and uFSH.
SETTING
Infertility centers providing treatment with ART.
PATIENT(S)
Patients undergoing IVF with or without ICSI.
INTERVENTION(S)
Controlled ovarian stimulation using uFSH or rFSH (follitropin alpha or follitropin beta).
MAIN OUTCOME MEASURE(S)
Primary: rate of clinical pregnancy per cycle. Secondary: rates of spontaneous abortion, multiple pregnancy, and severe ovarian hyperstimulation syndrome (OHSS); total gonadotropin dose; serum E(2) level and number of follicles at hCG administration; number of oocytes retrieved.
RESULT(S)
Eighteen trials were included in the meta-analysis. Subgroup analyses demonstrated higher pregnancy rates with both follitropins compared with uFSH. However, statistical significance was reached only in the follitropin alpha versus uFSH comparison in IVF cycles, with an additional pregnancy for every 19 patients treated. Fewer units of rFSH than uFSH achieved the same E(2) level and oocyte yield. No differences were found between treatments in rates of spontaneous abortion, OHSS, and multiple gestation.
CONCLUSION(S)
rFSH produced higher pregnancy rates per cycle than uFSH when follitropin alpha was used in IVF, and the total gonadotropin dose required was lower.
Topics: Abortion, Spontaneous; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Recombinant Proteins; Reproductive Techniques, Assisted; Sperm Injections, Intracytoplasmic; Treatment Outcome
PubMed: 11937121
DOI: 10.1016/s0015-0282(01)03246-0