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Journal of Assisted Reproduction and... Jul 2022The objective of this review is to define live birth rate (LBR) and clinical pregnancy rate (CPR) for women ≥ 40 undergoing ovulation induction (OI)/intrauterine... (Review)
Review
PURPOSE
The objective of this review is to define live birth rate (LBR) and clinical pregnancy rate (CPR) for women ≥ 40 undergoing ovulation induction (OI)/intrauterine insemination (IUI).
METHODS
A systematic review was performed in accordance with PRISMA guidelines using PubMed and Google Scholar. The primary and secondary outcomes of interest were LBR and CPR, respectively.
RESULTS
There were 636 studies screened of which 42 were included. In 8 studies which provided LBR for partner sperm, LBR/cycle ranged from 0 to 8.5% with majority being ≤ 4%. Cumulative LBR was 3.6 to 7.1% over 6 cycles with the majority of pregnancies in the first 4. In the four studies providing LBR for donor sperm cycles, LBR/cycle ranged from 3 to 7% with cumulative LBR of 12 to 24% over 6 cycles. The majority of pregnancies occurred in the first 6 cycles. There were three studies with LBR or CPR/cycle ≥ 1% for women ≥ 43. No studies provided data above this range for women ≥ 45. In 4 studies which compared OI/IUI and IVF, the LBR from IVF was 9.2 to 22% per cycle. In 7 studies which compared outcomes by stimulation protocol, no significant differences were seen.
CONCLUSION
For women ≥ 40 using homologous sperm, the highest probability of live birth is via IVF. However, if IVF is not an option, OI/IUI may be considered for up to 4 cycles in those using partner sperm or 6 cycles with donor sperm. For women > 45, OI/IUI is likely futile but a limited trial may be considered for psychological benefit while encouraging consideration of donor oocyte IVF or adoption. Use of gonadotropins does not appear to be more effective than oral agents in this age group.
Topics: Female; Fertilization in Vitro; Humans; Insemination; Insemination, Artificial; Male; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Semen
PubMed: 35731321
DOI: 10.1007/s10815-022-02551-8 -
The Cochrane Database of Systematic... Apr 2008Insemination with donor sperm is an option for couples for whom in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) has been unsuccessful, couples... (Review)
Review
BACKGROUND
Insemination with donor sperm is an option for couples for whom in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) has been unsuccessful, couples with azoospermia and for single women or same sex couples. Insemination of sperm can be done via cervical (CI) or intra-uterine (IUI) routes. IUI has been considered potentially more effective than CI as the sperm bypasses the cervical mucus and is deposited closer to the fallopian tubes. The cost and risks of IUI may be higher because of the need for sperm preparation and the introduction of foreign material into the uterus. Donor sperm used for artificial insemination is mainly cryopreserved, due to concerns about HIV transmission. However, cycle fecundity is higher for fresh sperm. Insemination is often combined with ovulatory stimulation, with either clomiphene or gonadotrophin. There may be risks associated with these therapies, such as higher multiple pregnancy rates.
OBJECTIVES
To determine whether pregnancy outcomes are improved using intra-uterine insemination in comparison to cervical insemination in women undergoing artificial insemination with donor sperm.
SEARCH STRATEGY
The following databases were searched: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL (The Cochrane Library) , MEDLINE, EMBASE, CINAHL and the reference lists of articles retrieved.
SELECTION CRITERIA
Randomised controlled trials comparing IUI with CI were included. Crossover studies were included if pre-crossover data was available.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction were carried out independently by two review authors (DB, JM). Authors of studies that potentially met the inclusion criteria were contacted, where possible if additional information was needed.
MAIN RESULTS
The search strategy found 232 articles. Fifteen studies potentially met the inclusion criteria. Four studies were included in this review. All the included studies used cryopreserved sperm in stimulated cycles. In two studies 134 women had gonadotrophin-stimulated cycles and in two studies 74 women had clomiphene-stimulated cycles. The evidence showed that IUI after 6 cycles significantly improved live birth rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.02 to 3.86) and pregnancy rates (OR 3.37, 95% CI 1.90 to 5.96) in comparison to cervical insemination. There was no statistically significant evidence of an effect on multiple pregnancies (OR 2.19, 95% CI 0.79 to 6.07) or miscarriages (relative risk (RR) 3.92, 95% CI 0.85 to 17.96).
AUTHORS' CONCLUSIONS
The findings of this systematic review support the use of IUI rather than CI in stimulated cycles using cryopreserved sperm for donor insemination.
Topics: Cervix Uteri; Cryopreservation; Female; Humans; Insemination, Artificial, Heterologous; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Semen Preservation; Uterus
PubMed: 18425862
DOI: 10.1002/14651858.CD000317.pub3 -
Iranian Journal of Reproductive Medicine Mar 2015Antibiotic therapies used in treatment of many diseases have adverse effects on fertility. This review analyzes previous comparative studies that surveyed the effects of... (Review)
Review
BACKGROUND
Antibiotic therapies used in treatment of many diseases have adverse effects on fertility. This review analyzes previous comparative studies that surveyed the effects of two common groups of antibiotics on male fertility.
OBJECTIVE
To evaluate histo-pathological effects of fluoroquinolones and aminoglycosides on sperm parameters and male reproductive tissue.
MATERIALS AND METHODS
Articles about the effects of aminoglycosides and fluoroquinolones on male infertility, sperm parameters, male reproductive tissue, and spermatogenesis in English and Persian languages published on Google Scholar and PubMed databases from January 2000 to December 2013 were assessed. Randomized controlled trials (RCTs) assessing the effects of aminoglycosides or fluoroquinolones on sperm parameters, artificial insemination, and male reproductive tract or RCTs comparing aminoglycosides vs. fluoroquinolones were eligible for inclusion. For ascertaining the reliability of study, data were extracted independently and in duplicate by two investigators.
RESULTS
Sperm viability was decreased significantly with streptomycin, gentamicin, and neomycin (p<0.001). Sperm motility was decreased significantly with gentamicin and neomycin (p<0.05). Total sperm count was significantly decreased with ofloxacin, gentamicin, streptomycin, and neomycin (p<0.022). There was significant decrease in post-thawing motility with low dose and high dose of ciprofloxacin. Testis weight was decreased with gentamicin and ofloxacin significantly (p<0.011). There was significant decrease in seminal vesicle weight with gentamicin, neomycin, and ofloxacin (p<0.022). Furthermore, changes in epididymis weight, percentage of total apoptotic cells, and diameter of seminiferous tubule were significant with all drugs including streptomycin, gentamicin, neomycin, and ofloxacin (p<0.05).
CONCLUSION
Streptomycin has less negative effects on cell's apoptosis and sperm parameters as compared to other drugs. Gentamicin has more detrimental effects so lesser dosage and duration is recommended. Fluoroquinolones showed negative effects on testis tissue and sperm parameters. Ciprofloxacin has less adverse effects than gentamicin in artificial insemination.
PubMed: 26000002
DOI: No ID Found -
Asian Journal of Andrology Jul 2013Male factor infertility affects 30%-50% of infertile couples worldwide, and there is an increasing interest in the optimal management of these patients. In studies... (Meta-Analysis)
Meta-Analysis Review
Male factor infertility affects 30%-50% of infertile couples worldwide, and there is an increasing interest in the optimal management of these patients. In studies comparing double and single intrauterine insemination (IUI), a trend towards higher pregnancy rates in couples with male factor infertility was observed. Therefore, we set out to perform a meta-analysis to examine the superiority of double versus single IUI with the male partner's sperm in couples with male factor infertility. An odds ratio (OR) of 95% confidence intervals (CIs) was calculated for the pregnancy rate. Outcomes were analysed by using the Mantel-Haesel or DerSimonian-Laird model according to the heterogeneity of the results. Overall, five trials involving 1125 IUI cycles were included in the meta-analysis. There was a two-fold increase in pregnancies after a cycle with a double IUI compared with a cycle with a single IUI (OR: 2.0; 95% CI: 1.07-3.75; P<0.03). Nevertheless, this result was mainly attributed to the presence of a large trial that weighted as almost 50% in the overall analysis. Sensitivity analysis, excluding this large trial, revealed only a trend towards higher pregnancy rates among double IUI cycles (OR: 1.58; 95% CI: 0.59-4.21), but without statistical significance (P=0.20). Our systematic review highlights that the available evidence regarding the use of double IUI in couples with male factor infertility is fragmentary and weak. Although there may be a trend towards higher pregnancy rates when the number of IUIs per cycle is increased, further large and well-designed randomized trials are needed to provide solid evidence to guide current clinical practice.
Topics: Clinical Trials as Topic; Female; Humans; Infertility, Male; Insemination, Artificial; Male; Pregnancy; Pregnancy Rate
PubMed: 23708457
DOI: 10.1038/aja.2013.4 -
Journal of Dairy Science Oct 2017The objective of this study was to conduct a systematic review to identify and assess evidence and knowledge gaps in published observational studies that have... (Review)
Review
The objective of this study was to conduct a systematic review to identify and assess evidence and knowledge gaps in published observational studies that have investigated the relationship between mastitis and pregnancy loss (PL) in dairy cows. PubMed and ScienceDirect were used to search pertinent peer-reviewed research reports of interest. Screening of research reports was conducted at 3 levels: titles, abstracts, and full-text articles. The search identified 651 records for initial screening. The final screening process identified 8 qualified articles for review after removing 10 duplicate records, 582 titles, 31 abstracts, and 20 full-text articles. Two studies produced strong epidemiologic evidence indicating that (1) exposure to clinical mastitis during early gestation (first 45 d of gestation) is associated with subsequent PL during the following 90 d; and (2) subclinical mastitis 1 to 30 d before artificial insemination (AI) is associated with subsequent PL at 35 to 41 d of gestation. An additional study showed that exposure to clinical mastitis during early lactation in combination with low body condition can increase the risk of PL in dairy cows; however, the interaction effect between clinical mastitis and low body condition on PL was considered weak. Four other studies produced inconclusive evidence indicating that mastitis is a predisposing factor for PL in dairy cows, as the exposure risk period for mastitis overlapped with the follow-up period for diagnosis of PL in dairy cows. Finally, one study failed to identify a relationship between mastitis and PL in dairy cows. Further research is needed to (1) support the hypothesis that mastitis in combination with low body condition score (or other exposure factors) can increase the risk of PL, (2) compare the effect of clinical versus subclinical mastitis on PL, (3) compare the effect of mastitis before breeding and during gestation on PL, and (4) compare the effect of mastitis on PL in dairy cows during different lactations.
Topics: Abortion, Veterinary; Animals; Cattle; Female; Insemination, Artificial; Lactation; Mastitis, Bovine; Observational Studies as Topic; Pregnancy
PubMed: 28780088
DOI: 10.3168/jds.2017-12711 -
European Journal of Obstetrics,... Jun 2017The cost of fertility treatment is expensive and interventions that reduce cost can lead to greater efficiency and fewer embryos transferred. Endometrial polyps... (Review)
Review
The cost of fertility treatment is expensive and interventions that reduce cost can lead to greater efficiency and fewer embryos transferred. Endometrial polyps contribute to infertility and are frequently removed prior to infertility treatment. It is unclear whether polypectomy reduces fertility treatment cost and if so, the magnitude of cost reduction afforded by the procedure. The aim of this study was to determine whether performing office or operative hysteroscopic polypectomy prior to infertility treatment would be cost-effective. PubMed, Embase, and Cochrane libraries were used to identify publications reporting pregnancy rates after hysteroscopic polypectomy. Studies were required to have a polypectomy treatment group and control group of patients with polyps that were not resected. The charges of infertility treatments and polypectomy were obtained through infertility organizations and a private healthcare cost reporting website. These charges were applied to a decision tree model over the range of pregnancy rates observed in the representative studies to calculate an average cost per clinical or ongoing pregnancy. A sensitivity analysis was conducted to assess cost savings of polypectomy over a range of pregnancy rates and polypectomy costs. Pre-treatment office or operative hysteroscopic polypectomy ultimately saved €6658 ($7480) and €728 ($818), respectively, of the average cost per clinical pregnancy in women treated with four cycles of intrauterine insemination. Polypectomy prior to intrauterine insemination was cost-effective for clinical pregnancy rates greater than 30.2% for office polypectomy and 52.6% for operative polypectomy and for polypectomy price <€4414 ($4959). Office polypectomy or operative polypectomy saved €15,854 ($17,813) and €6644 ($7465), respectively, from the average cost per ongoing pregnancy for in vitro fertilization/intracytoplasmic sperm injection treated women and was cost-effective for ongoing pregnancy rates greater than 26.4% (office polypectomy) and 31.7% (operative polypectomy) and polypectomy price <€6376 ($7164). These findings suggested that office or operative hysteroscopic polypectomy was cost-effective when performed prior to both intrauterine insemination and in vitro fertilization over a range of plausible pregnancy rates and procedural costs.
Topics: Cost-Benefit Analysis; Costs and Cost Analysis; Female; Fertilization in Vitro; Humans; Hysteroscopy; Infertility; Insemination, Artificial; Polyps; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Uterine Diseases
PubMed: 28445799
DOI: 10.1016/j.ejogrb.2017.04.025 -
Journal of Assisted Reproduction and... Jan 2014To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy of luteal phase support with vaginal progesterone in women undergoing intrauterine insemination (IUI).
METHODS
Systematic review and meta-analysis. Randomized controlled trials (RCT) comparing supplementation of luteal phase with vaginal progesterone among women undergoing IUI versus a control group were included. The main outcome assessed was live birth rate.
RESULTS
Five RCT met the inclusion criteria. In all 1,271 patients were included (951 IUI cycles in the progesterone group, 935 in the control group). Women treated with vaginal progesterone achieved significantly higher live birth rate (risk ratio [RR] 1.94, 95 % confidence interval [CI] 1.36 to 2.77,), and clinical pregnancy rate (RR 1.41, 95 % CI 1.14 to 1.76) as compared with controls. In the subgroup analysis per stimulation protocol, this beneficial effect of receiving progesterone was only observed in the group stimulated with gonadotropins (RR 2.28, 95 % CI 1.49 to 3.51), compared to the group stimulated with clomiphene citrate (CC) (RR 1.30, 95 % CI 0.68 to 2.50). No differences were observed in the miscarriage and multiple pregnancy rates.
CONCLUSIONS
The supplementation of luteal phase with vaginal progesterone significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction. Women receiving CC to induce ovulation do not seem to benefit from this treatment.
Topics: Administration, Intravaginal; Female; Humans; Infertility; Insemination, Artificial; Luteal Phase; Male; Pregnancy; Pregnancy Rate; Progesterone; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24189966
DOI: 10.1007/s10815-013-0127-6 -
The Cochrane Database of Systematic... Feb 2016Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently used fertility treatments for couples with male... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently used fertility treatments for couples with male subfertility. The use of these treatments has been subject of discussion. Knowledge on the effectiveness of fertility treatments for male subfertility with different grades of severity is limited. Possibly, couples are exposed to unnecessary or ineffective treatments on a large scale.
OBJECTIVES
To evaluate the effectiveness and safety of different fertility treatments (expectant management, timed intercourse (TI), IUI, IVF and ICSI) for couples whose subfertility appears to be due to abnormal sperm parameters.
SEARCH METHODS
We searched for all publications that described randomised controlled trials (RCTs) of the treatment for male subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO and the National Research Register from inception to 14 April 2015, and web-based trial registers from January 1985 to April 2015. We applied no language restrictions. We checked all references in the identified trials and background papers and contacted authors to identify relevant published and unpublished data.
SELECTION CRITERIA
We included RCTs comparing different treatment options for male subfertility. These were expectant management, TI (with or without ovarian hyperstimulation (OH)), IUI (with or without OH), IVF and ICSI. We included only couples with abnormal sperm parameters.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the review authors. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The quality of the evidence was rated using the GRADE methods. Primary outcomes were live birth and ovarian hyperstimulation syndrome (OHSS) per couple randomised.
MAIN RESULTS
The review included 10 RCTs (757 couples). The quality of the evidence was low or very low for all comparisons. The main limitations in the evidence were failure to describe study methods, serious imprecision and inconsistency. IUI versus TI (five RCTs)Two RCTs compared IUI with TI in natural cycles. There were no data on live birth or OHSS. We found no evidence of a difference in pregnancy rates (2 RCTs, 62 couples: odds ratio (OR) 4.57, 95% confidence interval (CI) 0.21 to 102, very low quality evidence; there were no events in one of the studies).Three RCTs compared IUI with TI both in cycles with OH. We found no evidence of a difference in live birth rates (1 RCT, 81 couples: OR 0.89, 95% CI 0.30 to 2.59; low quality evidence) or pregnancy rates (3 RCTs, 202 couples: OR 1.51, 95% CI 0.74 to 3.07; I(2) = 11%, very low quality evidence). One RCT reported data on OHSS. None of the 62 women had OHSS.One RCT compared IUI in cycles with OH with TI in natural cycles. We found no evidence of a difference in live birth rates (1 RCT, 44 couples: OR 3.14, 95% CI 0.12 to 81.35; very low quality evidence). Data on OHSS were not available. IUI in cycles with OH versus IUI in natural cycles (five RCTs)We found no evidence of a difference in live birth rates (3 RCTs, 346 couples: OR 1.34, 95% CI 0.77 to 2.33; I(2) = 0%, very low quality evidence) and pregnancy rates (4 RCTs, 399 couples: OR 1.68, 95% CI 1.00 to 2.82; I(2) = 0%, very low quality evidence). There were no data on OHSS. IVF versus IUI in natural cycles or cycles with OH (two RCTs)We found no evidence of a difference in live birth rates between IVF versus IUI in natural cycles (1 RCT, 53 couples: OR 0.77, 95% CI 0.25 to 2.35; low quality evidence) or IVF versus IUI in cycles with OH (2 RCTs, 86 couples: OR 1.03, 95% CI 0.43 to 2.45; I(2) = 0%, very low quality evidence). One RCT reported data on OHSS. None of the women had OHSS.Overall, we found no evidence of a difference between any of the groups in rates of live birth, pregnancy or adverse events (multiple pregnancy, miscarriage). However, most of the evidence was very low quality.There were no studies on IUI in natural cycles versus TI in stimulated cycles, IVF versus TI, ICSI versus TI, ICSI versus IUI (with OH) or ICSI versus IVF.
AUTHORS' CONCLUSIONS
We found insufficient evidence to determine whether there was any difference in safety and effectiveness between different treatments for male subfertility. More research is needed.
Topics: Birth Rate; Coitus; Female; Fertilization; Humans; Infertility, Male; Insemination, Artificial; Male; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 26915339
DOI: 10.1002/14651858.CD000360.pub5 -
The Cochrane Database of Systematic... Jan 2018The first-line treatment in donor sperm treatment consists of inseminations that can be done by intrauterine insemination (IUI) or by intracervical insemination (ICI). (Comparative Study)
Comparative Study Review
BACKGROUND
The first-line treatment in donor sperm treatment consists of inseminations that can be done by intrauterine insemination (IUI) or by intracervical insemination (ICI).
OBJECTIVES
To compare the effectiveness and safety of intrauterine insemination (IUI) and intracervical insemination (ICI) in women who start donor sperm treatment.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL in October 2016, checked references of relevant studies, and contacted study authors and experts in the field to identify additional studies. We searched PubMed, Google Scholar, the Grey literature, and five trials registers on 15 December 2017.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) reporting on IUI versus ICI in natural cycles or with ovarian stimulation, and RCTs comparing different cointerventions in IUI and ICI. We included cross-over studies if pre-cross-over data were available.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. We collected data on primary outcomes of live birth and multiple pregnancy rates, and on secondary outcomes of clinical pregnancy, miscarriage, and cancellation rates.
MAIN RESULTS
We included six RCTs (708 women analysed) on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated cycles, and two studies compared timing of IUI and ICI. There was very low-quality evidence; the main limitations were risk of bias due to poor reporting of study methods, and serious imprecision.IUI versus ICI in natural cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95% confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality evidence). There was only one live birth in this study (in the IUI group). IUI resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2 RCTs, 76 women; I² = 48%; very low-quality evidence).No multiple pregnancies or miscarriages occurred in this study.IUI versus ICI in gonadotrophin-stimulated cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in gonadotrophin-stimulated cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality evidence). This suggested that if the chance of a live birth following ICI in gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). IUI may be associated with higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). This suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk following IUI would be between 10% and 46%.We found insufficient evidence to determine whether there was any clear difference between the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95% CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I² = 50%; very low-quality evidence).Timing of IUI and ICIWe found no studies that reported on live birth rates.We found a higher clinical pregnancy rate when IUI was timed one day after a rise in blood levels of luteinising hormone (LH) compared to IUI two days after a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low-quality evidence). We found insufficient evidence to determine whether there was any clear difference in clinical pregnancy rates between ICI timed after a rise in urinary levels of LH versus a rise in basal temperature plus cervical mucus scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality evidence).Neither of these studies reported multiple pregnancy or miscarriage rates as outcomes.
AUTHORS' CONCLUSIONS
There was insufficient evidence to determine whether there was a clear difference in live birth rates between IUI and ICI in natural or gonadotrophin-stimulated cycles in women who started with donor sperm treatment. There was insufficient evidence available for the effect of timing of IUI or ICI on live birth rates. Very low-quality data suggested that in gonadotrophin-stimulated cycles, ICI may be associated with a higher clinical pregnancy rate than IUI, but also with a higher risk of multiple pregnancy rate. We concluded that the current evidence was too limited to choose between IUI or ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.
Topics: Body Temperature; Cervix Mucus; Female; Gonadotropins; Humans; Insemination, Artificial, Heterologous; Live Birth; Luteinizing Hormone; Menstrual Cycle; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Randomized Controlled Trials as Topic
PubMed: 29368795
DOI: 10.1002/14651858.CD000317.pub4 -
The Cochrane Database of Systematic... Nov 2015One-third of subfertile couples have no identifiable cause for their inability to conceive. In vitro fertilisation (IVF) is a widely accepted treatment for this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
One-third of subfertile couples have no identifiable cause for their inability to conceive. In vitro fertilisation (IVF) is a widely accepted treatment for this condition; however, this treatment is invasive and expensive and is associated with risks.
OBJECTIVES
To evaluate the effectiveness and safety of IVF compared with expectant management, unstimulated intrauterine insemination (IUI) or intrauterine insemination along with ovarian stimulation with gonadotropins (IUI + gonadotropins) or clomiphene (IUI + CC) or letrozole (IUI + letrozole) in improving pregnancy outcomes.
SEARCH METHODS
This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, first quarter), MEDLINE (1946 to May 2015), EMBASE (1985 to May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (May 2015) and reference lists of articles. We searched the following trial registries: clinicaltrials.gov (http://www.clinicaltrials.gov) and the World Health Organization International Trials Registry Platform search portal (http://www.who.int/trialsearch/Default.aspx). We searched the Web of Science (http://wokinfo.com/) as another source of trials and conference abstracts, OpenGrey (http://www.opengrey.eu/) for unpublished literature from Europe and the Latin American Caribbean Health Sciences Literature (LILACS) database (http://regional.bvsalud.org/php/index.php?lang=en). Moreover, we handsearched relevant conference proceedings and contacted study authors to ask about additional publications.Two review authors independently assessed trial eligibility, extracted data and assessed risk of bias. The primary review outcome was cumulative live birth rate. Multiple pregnancy and other adverse effects were secondary outcomes. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity by using the I(2) statistic. We assessed the overall quality of evidence for the main comparisons using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which the effectiveness of IVF in couples with unexplained subfertility was compared with that of other treatments, including expectant management, unstimulated IUI and stimulated IUI using gonadotropins or clomiphene or letrozole.Live birth rate (LBR) per woman was the primary outcome.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and quality of trials and evaluated the quality of the evidence by using GRADE criteria.
MAIN RESULTS
IVF versus expectant management (two RCTs):Live birth rate per woman was higher with IVF than with expectant management (odds ratio (OR) 22.00, 95% confidence interval (CI) 2.56 to 189.37, one RCT, 51 women, very low quality evidence). Multiple pregnancy rates (MPRs), ovarian hyperstimulation syndrome (OHSS) and miscarriage were not reported. IVF versus unstimulated IUI (two RCTs):Live birth rate was higher with IVF than with unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12, two RCTs, 156 women, I(2) = 60%, low quality evidence). There was no evidence of a difference between the groups in multiple pregnancy rates (OR 1.03, 95% CI 0.04 to 27.29, one RCT, 43 women, very low quality evidence) IVF versus IUI + ovarian stimulation with gonadotropins (three RCTs) or clomiphene (one RCT) or letrozole (no RCTs):Data from these trials could not be pooled because of high statistical heterogeneity (I(2) = 93.3%). Heterogeneity was eliminated when studies were stratified by pretreatment status.In trials comparing IVF versus IUI + gonadotropins among treatment-naive women, there was no conclusive evidence of a difference between the groups in live birth rates (OR 1.27, 95% CI 0.94 to 1.73, four RCTs, 745 women, I(2) = 8.0%, moderate-quality evidence). In women pretreated with IUI + clomiphene, a higher live birth rate was reported among those who underwent IVF than those given IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57, one RCT, 280 women, moderate-quality evidence).There was no conclusive evidence of a difference in live birth rates between IVF and IUI + CC in treatment-naive women (OR 2.51, 95% CI 0.96 to 6.55, one RCT, 103 women, low quality evidence).In treatment-naive women, there was no evidence of a difference in rates of multiple pregnancy between women who underwent IVF and those who received IUI + gonadotropins (OR 0.79, 95% CI 0.45 to 1.39, four RCTs, 745 women, I(2) = 0%, moderate quality evidence). There was no evidence of a difference in MPRs between women who underwent IVF compared with those given IUI + CC (OR 1.02, 95% CI 0.20 to 5.31, one RCT, 103 women, low-quality evidence).There was no evidence of a difference in ovarian hyperstimulation syndrome rate between treatment-naive women who underwent IVF and those given IUI + gonadotropins (OR 1.23, 95% CI 0.36 to 4.14, two RCTs, 221 women, low quality evidence). There was no evidence of a difference in OHSS rates between groups receiving IVF versus those receiving IUI + CC (OR 1.02, 95% CI 0.20 to 5.31, one RCT, 103 women, low-quality evidence).In treatment naive women, there was no evidence of a difference in miscarriage rates between IVF and IUI + CC (OR 1.16, 95% CI 0.44 to 3.02, one RCT, 103 women, low-quality evidence), nor between women treated with IVF versus those receiving IUI+ gonadotropins (OR 1.16, 95% CI 0.44 to 3.02, one RCT, 103 women).No studies compared IVF with IUI + letrozole.The quality of the evidence ranged from very low to moderate. The main limitation was serious imprecision resulting from small study numbers and low event rates.
AUTHORS' CONCLUSIONS
IVF may be associated with higher live birth rates than expectant management, but there is insufficient evidence to draw firm conclusions. IVF may also be associated with higher live birth rates than unstimulated IUI. In women pretreated with clomiphene + IUI, IVF appears to be associated with higher birth rates than IUI + gonadotropins. However in women who are treatment-naive there is no conclusive evidence of a difference in live birth rates between IVF and IUI + gonadotropins or between IVF and IUI + clomiphene. Adverse events associated with these interventions could not be adequately assessed owing to lack of evidence.
Topics: Clomiphene; Female; Fertility Agents, Female; Fertilization in Vitro; Gamete Intrafallopian Transfer; Humans; Infertility, Female; Insemination, Artificial; Live Birth; Ovulation Induction; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 26583517
DOI: 10.1002/14651858.CD003357.pub4