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Sports Medicine (Auckland, N.Z.) Oct 2020Concentrations of endogenous sex hormones fluctuate across the menstrual cycle (MC), which could have implications for exercise performance in women. At present, data... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concentrations of endogenous sex hormones fluctuate across the menstrual cycle (MC), which could have implications for exercise performance in women. At present, data are conflicting, with no consensus on whether exercise performance is affected by MC phase.
OBJECTIVE
To determine the effects of the MC on exercise performance and provide evidence-based, practical, performance recommendations to eumenorrheic women.
METHODS
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched for published experimental studies that investigated the effects of the MC on exercise performance, which included at least one outcome measure taken in two or more defined MC phases. All data were meta-analysed using multilevel models grounded in Bayesian principles. The initial meta-analysis pooled pairwise effect sizes comparing exercise performance during the early follicular phase with all other phases (late follicular, ovulation, early luteal, mid-luteal and late luteal) amalgamated. A more comprehensive analysis was then conducted, comparing exercise performance between all phases with direct and indirect pairwise effect sizes through a network meta-analysis. Results from the network meta-analysis were summarised by calculating the Surface Under the Cumulative Ranking curve (SUCRA). Study quality was assessed using a modified Downs and Black checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group.
RESULTS
Of the 78 included studies, data from 51 studies were eligible for inclusion in the initial pairwise meta-analysis. The three-level hierarchical model indicated a trivial effect for both endurance- and strength-based outcomes, with reduced exercise performance observed in the early follicular phase of the MC, based on the median pooled effect size (ES = - 0.06 [95% credible interval (CrI): - 0.16 to 0.04]). Seventy-three studies had enough data to be included in the network meta-analysis. The largest effect was identified between the early follicular and the late follicular phases of the MC (ES = - 0.14 [95% CrI: - 0.26 to - 0.03]). The lowest SUCRA value, which represents the likelihood that exercise performance is poor, or among the poorest, relative to other MC phases, was obtained for the early follicular phase (30%), with values for all other phases ranging between 53 and 55%. The quality of evidence for this review was classified as "low" (42%).
CONCLUSION
The results from this systematic review and meta-analysis indicate that exercise performance might be trivially reduced during the early follicular phase of the MC, compared to all other phases. Due to the trivial effect size, the large between-study variation and the number of poor-quality studies included in this review, general guidelines on exercise performance across the MC cannot be formed; rather, it is recommended that a personalised approach should be taken based on each individual's response to exercise performance across the MC.
Topics: Athletic Performance; Exercise; Female; Humans; Menstrual Cycle
PubMed: 32661839
DOI: 10.1007/s40279-020-01319-3 -
Orthopaedic Journal of Sports Medicine Jul 2017Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men. (Review)
Review
BACKGROUND
Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men.
PURPOSE
To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL.
STUDY DESIGN
Systematic review; Level of evidence, 4.
METHODS
Searches were conducted using MEDLINE (1946-August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included , , , , , , , and . Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.
RESULTS
Twenty-one studies totaling 68,758 participants were included: 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase.
CONCLUSION
The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.
PubMed: 28795075
DOI: 10.1177/2325967117718781 -
Journal of Applied Physiology... Dec 2023Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher... (Meta-Analysis)
Meta-Analysis Review
Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.
Topics: Female; Humans; Contraceptives, Oral; Menstrual Cycle; Hormones; Progesterone; Hypertrophy
PubMed: 37823207
DOI: 10.1152/japplphysiol.00346.2023 -
The Association between Vitamin D and Anti-Müllerian Hormone: A Systematic Review and Meta-Analysis.Nutrients May 2020Accumulating evidence from animal and human studies indicates a role for vitamin D in female reproductive physiology, and numerous clinical studies have suggested its... (Meta-Analysis)
Meta-Analysis Review
Accumulating evidence from animal and human studies indicates a role for vitamin D in female reproductive physiology, and numerous clinical studies have suggested its potential benefit for various aspects of human reproduction. Anti-Müllerian hormone (AMH) is an ovarian biomarker that plays an important role in folliculogenesis. It is the most sensitive ovarian reserve marker and is widely used clinically in reproductive medicine. While initial studies have suggested that vitamin D may be associated with ovarian reserve markers, including AMH, evidence has been conflicting. Currently, there is considerable debate in the field whether vitamin D has the capacity to influence ovarian reserve, as indicated by the AMH level. The current systematic review aims to evaluate and summarize the available evidence regarding the relationship between vitamin D and AMH. In total, 18 observational studies and 6 interventional studies were included in this systematic review. Cross-sectional studies have reported largely discrepant findings regarding an association between serum vitamin D and AMH levels, which are likely due to the heterogeneity in study populations, as well as the apparently complex relationship that may exist between vitamin D and AMH. However, meta-analysis of interventional studies performed herein that examined the effects of vitamin D supplementation on serum AMH levels indicates a cause-effect relationship between vitamin D and AMH, the direction of which appears to depend on a woman's ovulatory status. Serum AMH was significantly decreased following vitamin D supplementation in polycystic ovarian syndrome (PCOS) women (standardized mean difference (SMD) -0.53, 95% CI -0.91 to -0.15, < 0.007), while it was significantly increased following vitamin D supplementation in ovulatory women without PCOS (SMD 0.49, 95% CI 0.17 to 0.80, = 0.003). In conclusion, the results of this systematic review demonstrate that the relationship between vitamin D and AMH is a complex one, and large, randomized trials of vitamin D supplementation focusing on different vitamin D status ranges are necessary to gain more insight into the nature of this relationship and the potential benefit of vitamin D to female reproduction in general.
Topics: Animals; Anti-Mullerian Hormone; Dietary Supplements; Female; Humans; Ovarian Reserve; Ovulation; Polycystic Ovary Syndrome; Reproduction; Vitamin D
PubMed: 32481491
DOI: 10.3390/nu12061567 -
Fertility and Sterility Dec 2016Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to... (Review)
Review
Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to identify who is at high risk, how to prevent OHSS, and the treatment for existing OHSS.
Topics: Female; Humans; Infertility; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation; Ovulation Induction; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome
PubMed: 27678032
DOI: 10.1016/j.fertnstert.2016.08.048 -
The Cochrane Database of Systematic... Aug 2018As many as one in six couples will encounter problems with fertility, defined as failure to achieve a clinical pregnancy after regular intercourse for 12 months.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As many as one in six couples will encounter problems with fertility, defined as failure to achieve a clinical pregnancy after regular intercourse for 12 months. Increasingly, couples are turning to assisted reproductive technology (ART) for help with conceiving and ultimately giving birth to a healthy live baby of their own. Fertility treatments are complex, and each ART cycle consists of several steps. If one of these steps is incorrectly applied, the stakes are high as conception may not occur. With this in mind, it is important that each step of the ART cycle is supported by good evidence from well-designed studies.
OBJECTIVES
To summarise the evidence from Cochrane systematic reviews on procedures and treatment options available to couples with subfertility undergoing assisted reproductive technology (ART) procedures.
METHODS
Published Cochrane systematic reviews of couples undergoing ART procedures (in vitro fertilisation or intracytoplasmic sperm injection) were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation, for future inclusion.The primary outcome of the overview was live birth or the composite outcome live birth or ongoing pregnancy, as reported by the included reviews. Our secondary outcomes were clinical pregnancy, multiple pregnancy, miscarriage, and ovarian hyperstimulation syndrome. We excluded studies of intrauterine insemination and ovulation induction.We undertook selection of systematic reviews, data extraction, and quality assessment in duplicate. We assessed review quality by using the AMSTAR tool. We organised reviews by their relevance to specific stages in the ART cycle. We summarised their findings in the text and reported data for each outcome in 'Additional tables'.
MAIN RESULTS
We included 68 systematic reviews published in the Cochrane Library up to May 2018. All were of high quality. These reviews identified 38 interventions that were effective (n = 23) or promising (n = 15), and they identified 19 interventions that were ineffective (n = 2) or possibly ineffective (n = 17). For 15 interventions, review authors were unable to draw conclusions owing to lack of evidence.We identified an additional 11 protocols and four titles for future inclusion in this overview.
AUTHORS' CONCLUSIONS
This overview provides the most up-to-date evidence on ART cycles from systematic reviews of randomised controlled trials. Fertility treatments are costly, and the stakes are high. Using the best available evidence to optimise outcomes is best practice. Evidence from this overview could be used to develop clinical practice guidelines and protocols that can be applied in daily clinical practice to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation, and ovarian hyperstimulation syndrome.
Topics: Databases, Bibliographic; Humans; Infertility; Libraries, Digital; Reproductive Techniques, Assisted; Systematic Reviews as Topic
PubMed: 30117155
DOI: 10.1002/14651858.CD010537.pub5 -
Frontiers in Endocrinology 2021Diet has been reported as the first-line management of polycystic ovary syndrome (PCOS). However, the relationship between diet and fertility in PCOS is still... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Diet has been reported as the first-line management of polycystic ovary syndrome (PCOS). However, the relationship between diet and fertility in PCOS is still controversial. This meta-analysis aimed to evaluate whether diet could promote reproductive health in women with PCOS while providing evidence-based nutrition advice for clinical practice.
METHODS
Seven databases, including Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, and some Chinese database, were searched up to January 31, 2021. Randomized controlled trials evaluating the effects of diet in women with PCOS were included. Based on a preregistered protocol (PROSPERO CRD42019140454), the systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two reviewers made study selection, data extraction and bias assessment independently. Risk ratios and mean difference with 95% confidence intervals were assessed by a random-effects model. Statistical heterogeneity within comparisons was evaluated by Cochran's Q test and quantified by the I-squared ( ) statistic.
RESULTS
Twenty RCTs with 1113 participants were included. Results showed diet significantly related to improved fertility outcomes (increasing clinical pregnancy, ovulation and menstrual regularity rate; reducing miscarriage rate), reproductive endocrine [increasing sex hormone-binding globulin (SHBG); decreasing Anti-Müllerian Hormone (AMH), free androgen index (FAI), total testosterone (T)] and clinical hyperandrogenism (hirsutism assessed by Ferriman-Gallwey score) in PCOS. Specifically, subgroup analyses indicated low-carbohydrate diets were superior in optimizing reproductive outcomes and calorie restriction was critical in ameliorating hyperandrogenism. Additionally, the positive effects were associated with the treatment duration. The longer the duration, the greater the improvement was.
CONCLUSION
Overall, diet is an effective intervention for improving fertility health, thus professional and dynamic dietary advice should be offered to all PCOS patients, based on the changeable circumstances, personal needs and expectations of the individuals.
Topics: Databases, Factual; Diet; Female; Humans; Polycystic Ovary Syndrome; Reproductive Health
PubMed: 34790167
DOI: 10.3389/fendo.2021.735954 -
The Cochrane Database of Systematic... Mar 2014This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis. (Review)
Review
BACKGROUND
This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis.
OBJECTIVES
The objective of this overview was to summarise the evidence from Cochrane systematic reviews on treatment options for women with pain or subfertility associated with endometriosis.
METHODS
Published Cochrane systematic reviews reporting pain or fertility outcomes in women with clinically diagnosed endometriosis were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation (protocols and titles) for future inclusion. The reviews, protocols and titles were identified by searching the Cochrane Database of Systematic Reviews and Archie (the Cochrane information management system) in March 2014.Pain-related outcomes of the overview were pain relief, clinical improvement or resolution and pain recurrence. Fertility-related outcomes were live birth, clinical pregnancy, ongoing pregnancy, miscarriage and adverse events.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed using the AMSTAR tool. The quality of the evidence for each outcome was assessed using GRADE methods. Review findings were summarised in the text and the data for each outcome were reported in 'Additional tables'.
MAIN RESULTS
Seventeen systematic reviews published in The Cochrane Library were included. All the reviews were high quality. The quality of the evidence for specific comparisons ranged from very low to moderate. Limitations in the evidence included risk of bias in the primary studies, inconsistency between the studies, and imprecision in effect estimates. Pain relief (14 reviews) Gonadotrophin-releasing hormone (GnRH) analogues One systematic review reported low quality evidence of an overall benefit for GnRH analogues compared with placebo or no treatment. Ovulation suppression Five systematic reviews reported on medical treatment using ovulation suppression. There was moderate quality evidence that the levonorgestrel-releasing intrauterine system (LNG-IUD) was more effective than expectant management, and very low quality evidence that danazol was more effective than placebo. There was no consistent evidence of a difference in effectiveness between oral contraceptives and goserelin, estrogen plus progestogen and placebo, or progestogens and placebo, though in all cases the relevant evidence was of low or very low quality. Non-steroidal anti-inflammatory drugs (NSAIDS)A review of NSAIDs reported inconclusive evidence of a benefit in symptom relief compared with placebo. Surgical interventions There were two reviews of surgical interventions. One reported moderate quality evidence of a benefit in pain relief following laparoscopic surgery compared to diagnostic laparoscopy only. The other reported very low quality evidence that recurrence rates of endometriomata were lower after excisional surgery than after ablative surgery. Post-surgical medical interventions Two reviews reported on post-surgical medical interventions. Neither found evidence of an effect on pain outcomes, though in both cases the evidence was of low or very low quality. Alternative medicine There were two systematic reviews of alternative medicine. One reported evidence of a benefit from auricular acupuncture compared to Chinese herbal medicine, and the other reported no evidence of a difference between Chinese herbal medicine and danazol. In both cases the evidence was of low or very low quality. Anti-TNF-α drugs One review found no evidence of a difference in effectiveness between anti-TNF-α drugs and placebo. However, the evidence was of low quality. Reviews reporting fertility outcomes (8 reviews) Medical interventions Four reviews reported on medical interventions for improving fertility in women with endometriosis. One compared three months of GnRH agonists with a control in women undergoing assisted reproduction and found very low quality evidence of an increase in clinical pregnancies in the treatment group. There was no evidence of a difference in effectiveness between the interventions in the other three reviews, which compared GnRH agonists versus antagonists, ovulation suppression versus placebo or no treatment, and pre-surgical medical therapy versus surgery alone. In all cases the evidence was of low or very low quality. Surgical interventions Three reviews reported on surgical interventions. There was moderate quality evidence that both live births or ongoing pregnancy rates and clinical pregnancy rates were higher after laparoscopic surgery than after diagnostic laparoscopy alone. There was low quality evidence of no difference in effectiveness between surgery and expectant management for endometrioma. One review found low quality evidence that excisional surgery resulted in higher clinical pregnancy rates than drainage or ablation of endometriomata. Post-surgical interventions Two reviews reported on post-surgical medical interventions. They found no evidence of an effect on clinical pregnancy rates. The evidence was of low or very low quality. Alternative medicine A review of Chinese herbal medicine in comparison with gestrinone found no evidence of a difference between the groups in clinical pregnancy rates. However, the evidence was of low quality. Adverse events Reviews of GnRH analogues and of danazol reported that the interventions were associated with higher rates of adverse effects than placebo; and depot progestagens were associated with higher rates of adverse events than other treatments. Chinese herbal medicine was associated with fewer side effects than gestrinone or danazol.Three reviews reported miscarriage as an outcome. No difference was found between surgical and diagnostic laparoscopy, between GnRH agonists and antagonists, or between aspiration of endometrioma and expectant management. However, in all cases the quality of the evidence was of low quality.
AUTHORS' CONCLUSIONS
For women with pain and endometriosis, suppression of menstrual cycles with gonadotrophin-releasing hormone (GnRH) analogues, the levonorgestrel-releasing intrauterine system (LNG-IUD) and danazol were beneficial interventions. Laparoscopic treatment of endometriosis and excision of endometriomata were also associated with improvements in pain. The evidence on NSAIDs was inconclusive. There was no evidence of benefit with post-surgical medical treatment.In women with endometriosis undergoing assisted reproduction, three months of treatment with GnRH agonist improved pregnancy rates. Excisional surgery improved spontaneous pregnancy rates in the nine to 12 months after surgery compared to ablative surgery. Laparoscopic surgery improved live birth and pregnancy rates compared to diagnostic laparoscopy alone. There was no evidence that medical treatment improved clinical pregnancy rates.Evidence on harms was scanty, but GnRH analogues, danazol and depot progestagens were associated with higher rates than other interventions.
Topics: Acupuncture, Ear; Anti-Inflammatory Agents, Non-Steroidal; Drugs, Chinese Herbal; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; NM23 Nucleoside Diphosphate Kinases; Ovulation Inhibition; Pelvic Pain; Review Literature as Topic
PubMed: 24610050
DOI: 10.1002/14651858.CD009590.pub2 -
Fertility and Sterility Feb 2009To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to... (Review)
Review
OBJECTIVE
To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research.
DESIGN
Literature review and expert consensus.
SETTING
Professional society.
PATIENTS
None.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS.
RESULT(S)
The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence.
CONCLUSION(S)
Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.
Topics: Biomarkers; Diagnosis, Differential; Evidence-Based Medicine; Female; Health Status Indicators; Humans; Hyperandrogenism; Menstruation Disturbances; Ovarian Function Tests; Ovary; Ovulation; Phenotype; Polycystic Ovary Syndrome; Predictive Value of Tests; Terminology as Topic
PubMed: 18950759
DOI: 10.1016/j.fertnstert.2008.06.035 -
The Cochrane Database of Systematic... Jul 2017Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008.
OBJECTIVES
To compare the effectiveness and safety of natural cycle FET, HT cycle FET and ovulation induction cycle FET, and compare subtypes of these regimens.
SEARCH METHODS
On 13 December 2016 we searched databases including Cochrane Gynaecology and Fertility's Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. Other search sources were trials registers and reference lists of included studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth rates and miscarriage.
MAIN RESULTS
We included 18 RCTs comparing different cycle regimens for FET in 3815 women. The quality of the evidence was low or very low. The main limitations were failure to report important clinical outcomes, poor reporting of study methods and imprecision due to low event rates. We found no data specific to non-ovulatory women. 1. Natural cycle FET comparisons Natural cycle FET versus HT FETNo study reported live birth rates, miscarriage or ongoing pregnancy.There was no evidence of a difference in multiple pregnancy rates between women in natural cycles and those in HT FET cycle (odds ratio (OR) 2.48, 95% confidence interval (CI) 0.09 to 68.14, 1 RCT, n = 21, very low-quality evidence). Natural cycle FET versus HT plus GnRHa suppressionThere was no evidence of a difference in rates of live birth (OR 0.77, 95% CI 0.39 to 1.53, 1 RCT, n = 159, low-quality evidence) or multiple pregnancy (OR 0.58, 95% CI 0.13 to 2.50, 1 RCT, n = 159, low-quality evidence) between women who had natural cycle FET and those who had HT FET cycles with GnRHa suppression. No study reported miscarriage or ongoing pregnancy. Natural cycle FET versus modified natural cycle FET (human chorionic gonadotrophin (HCG) trigger)There was no evidence of a difference in rates of live birth (OR 0.55, 95% CI 0.16 to 1.93, 1 RCT, n = 60, very low-quality evidence) or miscarriage (OR 0.20, 95% CI 0.01 to 4.13, 1 RCT, n = 168, very low-quality evidence) between women in natural cycles and women in natural cycles with HCG trigger. However, very low-quality evidence suggested that women in natural cycles (without HCG trigger) may have higher ongoing pregnancy rates (OR 2.44, 95% CI 1.03 to 5.76, 1 RCT, n = 168). There were no data on multiple pregnancy. 2. Modified natural cycle FET comparisons Modified natural cycle FET (HCG trigger) versus HT FETThere was no evidence of a difference in rates of live birth (OR 1.34, 95% CI 0.88 to 2.05, 1 RCT, n = 959, low-quality evidence) or ongoing pregnancy (OR 1.21, 95% CI 0.80 to 1.83, 1 RCT, n = 959, low-quality evidence) between women in modified natural cycles and those who received HT. There were no data on miscarriage or multiple pregnancy. Modified natural cycle FET (HCG trigger) versus HT plus GnRHa suppressionThere was no evidence of a difference between the two groups in rates of live birth (OR 1.11, 95% CI 0.66 to 1.87, 1 RCT, n = 236, low-quality evidence) or miscarriage (OR 0.74, 95% CI 0.25 to 2.19, 1 RCT, n = 236, low-quality evidence) rates. There were no data on ongoing pregnancy or multiple pregnancy. 3. HT FET comparisons HT FET versus HT plus GnRHa suppressionHT alone was associated with a lower live birth rate than HT with GnRHa suppression (OR 0.10, 95% CI 0.04 to 0.30, 1 RCT, n = 75, low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 0.64, 95% CI 0.37 to 1.12, 6 RCTs, n = 991, I = 0%, low-quality evidence) or ongoing pregnancy (OR 1.72, 95% CI 0.61 to 4.85, 1 RCT, n = 106, very low-quality evidence).There were no data on multiple pregnancy. 4. Comparison of subtypes of ovulation induction FET Human menopausal gonadotrophin(HMG) versus clomiphene plus HMG HMG alone was associated with a higher live birth rate than clomiphene combined with HMG (OR 2.49, 95% CI 1.07 to 5.80, 1 RCT, n = 209, very low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 1.33, 95% CI 0.35 to 5.09,1 RCT, n = 209, very low-quality evidence) or multiple pregnancy (OR 1.41, 95% CI 0.31 to 6.48, 1 RCT, n = 209, very low-quality evidence).There were no data on ongoing pregnancy.
AUTHORS' CONCLUSIONS
This review did not find sufficient evidence to support the use of one cycle regimen in preference to another in preparation for FET in subfertile women with regular ovulatory cycles. The most common modalities for FET are natural cycle with or without HCG trigger or endometrial preparation with HT, with or without GnRHa suppression. We identified only four direct comparisons of these two modalities and there was insufficient evidence to support the use of either one in preference to the other.
Topics: Clomiphene; Cryopreservation; Embryo Transfer; Endometrium; Estrogens; Female; Fertility Agents, Female; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Randomized Controlled Trials as Topic
PubMed: 28675921
DOI: 10.1002/14651858.CD003414.pub3