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PloS One 2023Eumenorrheic women experience cyclic variations in sex hormones attributed to the menstrual cycle (MC) which can impact anterior cruciate ligament (ACL) properties, knee...
Effects of the menstrual cycle phase on anterior cruciate ligament neuromuscular and biomechanical injury risk surrogates in eumenorrheic and naturally menstruating women: A systematic review.
BACKGROUND
Eumenorrheic women experience cyclic variations in sex hormones attributed to the menstrual cycle (MC) which can impact anterior cruciate ligament (ACL) properties, knee laxity, and neuromuscular function. This systematic review aimed to examine the effects of the MC on ACL neuromuscular and biomechanical injury risk surrogates during dynamic tasks, to establish whether a particular MC phase predisposes women to greater ACL injury risk.
METHODS
PubMed, Medline, SPORTDiscus, and Web of Science were searched (May-July 2021) for studies that investigated the effects of the MC on ACL neuromuscular and biomechanical injury risk surrogates. Inclusion criteria were: 1) injury-free women (18-40 years); 2) verified MC phases via biochemical analysis and/or ovulation kits; 3) examined neuromuscular and/or biomechanical injury risk surrogates during dynamic tasks; 4) compared ≥1 outcome measure across ≥2 defined MC phases.
RESULTS
Seven of 418 articles were included. Four studies reported no significant differences in ACL injury risk surrogates between MC phases. Two studies showed evidence the mid-luteal phase may predispose women to greater risk of non-contact ACL injury. Three studies reported knee laxity fluctuated across the MC; two of which demonstrated MC attributed changes in knee laxity were associated with changes in knee joint loading (KJL). Study quality (Modified Downs and Black Checklist score: 7-9) and quality of evidence were low to very low (Grading of Recommendations Assessment Development and Evaluation: very low).
CONCLUSION
It is inconclusive whether a particular MC phase predisposes women to greater non-contact ACL injury risk based on neuromuscular and biomechanical surrogates. Practitioners should be cautious manipulating their physical preparation, injury mitigation, and screening practises based on current evidence. Although variable (i.e., magnitude and direction), MC attributed changes in knee laxity were associated with changes in potentially hazardous KJLs. Monitoring knee laxity could therefore be a viable strategy to infer possible ACL injury risk.
Topics: Humans; Female; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Menstruation; Joint Instability; Knee Joint; Menstrual Cycle; Biomechanical Phenomena
PubMed: 36701354
DOI: 10.1371/journal.pone.0280800 -
Nutrients Jan 2023Obesity is an established risk factor for the development of polycystic ovary syndrome (PCOS), especially phenotype A. PCOS is an important cause of fertility disorders... (Review)
Review
Obesity is an established risk factor for the development of polycystic ovary syndrome (PCOS), especially phenotype A. PCOS is an important cause of fertility disorders in a large group of women of reproductive age. For many years, effective methods of treating hormonal disorders associated with PCOS have been sought in order to restore ovulation with regular menstrual cycles. Numerous studies support obesity treatment as an effective therapeutic method for many women. A seemingly simple method of treatment may prove to be particularly difficult in this group of women. The reason for this may be the lack of recognition the primary cause of obesity development or the occurrence of a vicious circle of disease. Primary causes of developing obesity may be emotional eating (EE) and eating disorders (EDs), such as binge eating disorder (BED) and its extreme form, addictive eating, as well as night eating syndrome (NES). All of these are caused by impaired function of the reward system. Consequently, these disorders can develop or be exacerbated in women with obesity and PCOS as a result of depression and anxiety related to hirsutism and fertility disturbances. Therefore, for the effective treatment of obesity, it is very important to recognize and treat EE, BED, and NES, including the appropriate selection of pharmacotherapy and psychotherapy. Therefore, the aim of our manuscript is to analyze the available data on the relationships between EE, BED, NES, obesity, and PCOS and their impact on the treatment of obesity in women with PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Binge-Eating Disorder; Night Eating Syndrome; Hirsutism; Obesity
PubMed: 36678165
DOI: 10.3390/nu15020295 -
The Cochrane Database of Systematic... May 2018Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective as the first-line treatment clomiphene citrate (CC).
OBJECTIVES
To evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination (IUI).
SEARCH METHODS
We searched the following sources from inception to November 2017 to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, Pubmed, LILACS, Web of Knowledge, the World Health Organization (WHO) clinical trials register and Clinicaltrials.gov. We also searched the references of relevant articles. We did not restrict the searches by language or publication status.
SELECTION CRITERIA
We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted the data and assessed risks of bias. We pooled studies where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth and OHSS. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy. We assessed the quality of the evidence for each comparison using GRADE methods.
MAIN RESULTS
This is a substantive update of a previous review. We identified 16 additional studies for the 2018 update. We include 42 RCTs (7935 women). The aromatase inhibitor letrozole was used in all studies.Letrozole compared to clomiphene citrate (CC) with or without adjuncts followed by timed intercourseLive birth rates were higher with letrozole (with or without adjuncts) compared to clomiphene citrate (with our without adjuncts) followed by timed intercourse (OR 1.68, 95% CI 1.42 to 1.99; 2954 participants; 13 studies; I = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-quality evidence). There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.00; 2536 participants; 12 studies; I = 0%; high-quality evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.56, 95% CI 1.37 to 1.78; 4629 participants; 25 studies; I = 1%; NNTB = 10; moderate-quality evidence). There is little or no difference between treatment groups in the rate of miscarriage by pregnancy (20% with CC versus 19% with letrozole; OR 0.94, 95% CI 0.70 to 1.26; 1210 participants; 18 studies; I = 0%; high-quality evidence) and multiple pregnancy rate (1.7% with CC versus 1.3% with letrozole; OR 0.69, 95% CI 0.41 to 1.16; 3579 participants; 17 studies; I = 0%; high-quality evidence). However, a funnel plot showed mild asymmetry, indicating that some studies in favour of clomiphene might be missing.Letrozole compared to laparoscopic ovarian drillingThere is low-quality evidence that live birth rates are similar with letrozole or laparoscopic ovarian drilling (OR 1.38, 95% CI 0.95 to 2.02; 548 participants; 3 studies; I = 23%; low-quality evidence). There is insufficient evidence for a difference in OHSS rates (RD 0.00, 95% CI -0.01 to 0.01; 260 participants; 1 study; low-quality evidence). There is low-quality evidence that pregnancy rates are similar (OR 1.28, 95% CI 0.94 to 1.74; 774 participants; 5 studies; I = 0%; moderate-quality evidence). There is insufficient evidence for a difference in miscarriage rate by pregnancy (OR 0.66, 95% CI 0.30 to 1.43; 240 participants; 5 studies; I = 0%; moderate-quality evidence), or multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 548 participants; 3 studies; I = 0%; low-quality evidence).Additional comparisons were made for Letrozole versus placebo, Selective oestrogen receptor modulators (SERMS) followed by intrauterine insemination (IUI), follicle stimulating hormone (FSH), Anastrozole, as well as dosage and administration protocols. There is insufficient evidence for a difference in either group of treatment due to a limited number of studies. Hence more research is necessary.
AUTHORS' CONCLUSIONS
Letrozole appears to improve live birth and pregnancy rates in subfertile women with anovulatory polycystic ovary syndrome, compared to clomiphene citrate. There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate. There is high-quality evidence of no difference in miscarriage rates or multiple pregnancy rates. There is low-quality evidence of no difference in live birth and pregnancy rates between letrozole and laparoscopic ovarian drilling, although there were few relevant studies. For the 2018 update, we added good-quality trials, upgrading the quality of the evidence.
Topics: Abortion, Spontaneous; Anastrozole; Aromatase Inhibitors; Birth Rate; Clomiphene; Coitus; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; Nitriles; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Triazoles
PubMed: 29797697
DOI: 10.1002/14651858.CD010287.pub3 -
Medicine Apr 2020Polycystic ovary syndrome (PCOS) affects reproductive-aged women and is associated with increased prevalence of serious clinical problems including: reproductive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) affects reproductive-aged women and is associated with increased prevalence of serious clinical problems including: reproductive implications, metabolic dysfunction, and cardiovascular risk. Physical activity offers several health benefits for women with PCOS. The aim of this systematic review was to synthesize evidence on the effect of different types of exercise on reproductive function and body composition for women with PCOS.
METHODS
This was a systematic review and meta-analysis of randomized controlled trials (RCTs) following recommended review methods. We searched 6 databases: Cumulative Index of Nursing and Allied Health Literature; Embase; MEDLINE (via Ovid); PubMed; Sport Discus; and Web of Science; and we developed search strategies using a combination of Medical Subject Headings terms and text words related to exercise interventions for women with PCOS. There was no restriction on language or publication year. The search was conducted on April 16, 2019 and updated on November 15, 2019. Two authors independently screened citations, determined risk of bias and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation. We conducted meta-analyses following recommended guidelines, and report results using standardized mean difference (SMD).
RESULTS
Ten RCTs (n = 533) were included in this review. Studies tested the following interventions: aerobic, resistance, and combined (aerobic/resistance) training programs. Most studies were small (average 32, range 15-124 participants), and of relatively short duration (8-32 weeks). There was high heterogeneity for outcomes of reproductive function (menstrual cycle, ovulation, and fertility). We noted low certainty evidence for little to no effect of exercise on reproductive hormones and moderate certainty evidence that aerobic exercise reduced body mass index (BMI) in women with PCOS: BMI SMD -0.35, 95% confidence interval -0.56 to -0.14, P = .001.
CONCLUSION
For women with PCOS, evidence is limited to discern the effect of exercise on major health outcomes (e.g., reproductive function). There is moderate certainty evidence that aerobic exercise alone is beneficial for reducing BMI in women with PCOS. Future studies should be conducted with longer duration, larger sample sizes, and should provide detailed information on menstrual cycle and fertility outcomes.PROSPERO Systematic review registration: 2017 CRD42017058869.
Topics: Exercise Therapy; Female; Humans; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 32311937
DOI: 10.1097/MD.0000000000019644 -
Human Reproduction Update Feb 2021Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance.
OBJECTIVE AND RATIONALE
To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF.
SEARCH METHODS
Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology.
OUTCOMES
A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost.
WIDER IMPLICATIONS
This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with 'freeze-all' strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF.
Topics: Female; Fertilization in Vitro; Humans; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 33146690
DOI: 10.1093/humupd/dmaa035 -
The Cochrane Database of Systematic... Sep 2022Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI, letrozole, is at least as effective as the first-line treatment clomiphene citrate (CC), a selective oestrogen receptor modulator (SERM).
OBJECTIVES
To evaluate the effectiveness and safety of AIs (letrozole) (with or without adjuncts) compared to SERMs (with or without adjuncts) for infertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination.
SEARCH METHODS
We searched the following sources, from their inception to 4 November 2021, to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO. We also checked reference lists of relevant trials, searched the trial registers and contacted experts in the field for any additional trials. We did not restrict the searches by language or publication status.
SELECTION CRITERIA
We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted the data and assessed risks of bias using RoB 1. We pooled trials where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth rate and OHSS rate. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy rates. We assessed the certainty of the evidence for each comparison using GRADE methods.
MAIN RESULTS
This is a substantive update of a previous review; of six previously included trials, we excluded four from this update and moved two to 'awaiting classification' due to concerns about validity of trial data. We included five additional trials for this update that now includes a total of 41 RCTs (6522 women). The AI, letrozole, was used in all trials. Letrozole compared to SERMs with or without adjuncts followed by timed intercourse Live birth rates were higher with letrozole (with or without adjuncts) compared to SERMs followed by timed intercourse (OR 1.72, 95% CI 1.40 to 2.11; I = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; 11 trials, 2060 participants; high-certainty evidence). This suggests that in women with a 20% chance of live birth using SERMs, the live birth rate in women using letrozole with or without adjuncts would be 27% to 35%. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.01; I = 0%; 10 trials, 1848 participants; high-certainty evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.69, 95% CI 1.45 to 1.98; I = 0%; NNTB = 10; 23 trials, 3321 participants; high-certainty evidence). This suggests that in women with a 24% chance of clinical pregnancy using SERMs, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 32% to 39%. There is little or no difference between treatment groups in the rate of miscarriage per pregnancy (25% with SERMs versus 24% with letrozole: OR 0.94, 95% CI 0.66 to 1.32; I = 0%; 15 trials, 736 participants; high-certainty evidence) and multiple pregnancy rate (2.2% with SERMs versus 1.6% with letrozole: OR 0.74, 95% CI 0.42 to 1.32; I = 0%; 14 trials, 2247 participants; high-certainty evidence). However, a funnel plot showed mild asymmetry, indicating that some trials in favour of SERMs might be missing. Letrozole compared to laparoscopic ovarian drilling (LOD) One trial reported very low-certainty evidence that live birth rates may be higher with letrozole compared to LOD (OR 2.07, 95% CI 0.99 to 4.32; 1 trial, 141 participants; very low-certainty evidence). This suggests that in women with a 22% chance of live birth using LOD with or without adjuncts, the live birth rate in women using letrozole with or without adjuncts would be 24% to 47%. No trial reported OHSS rates. Due to the low-certainty evidence we are uncertain if letrozole improves pregnancy rates compared to LOD (OR 1.47, 95% CI 0.95 to 2.28; I² = 0%; 3 trials, 367 participants; low-certainty evidence). This suggests that in women with a 29% chance of clinical pregnancy using LOD with or without adjuncts, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 28% to 45%. There seems to be no evidence of a difference in miscarriage rates per pregnancy comparing letrozole to LOD (OR 0.65, 95% CI 0.22 to 1.92; I² = 0%; 3 trials, 122 participants; low-certainty evidence). This also applies to multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 1 trial, 141 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Letrozole appears to improve live birth rates and pregnancy rates in infertile women with anovulatory PCOS, compared to SERMs, when used for ovulation induction, followed by intercourse. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs. There was high-certainty evidence of no difference in miscarriage rate and multiple pregnancy rate. We are uncertain if letrozole increases live birth rates compared to LOD. In this update, we added good quality trials and removed trials with concerns over data validity, thereby upgrading the certainty of the evidence base.
Topics: Abortion, Spontaneous; Anovulation; Aromatase Inhibitors; Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Selective Estrogen Receptor Modulators
PubMed: 36165742
DOI: 10.1002/14651858.CD010287.pub4 -
The Cochrane Database of Systematic... Nov 2017Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with increased risk of cardiovascular disease and diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation.
OBJECTIVES
To evaluate the effectiveness and safety of insulin-sensitising drugs in improving reproductive and metabolic outcomes for women with PCOS undergoing ovulation induction.
SEARCH METHODS
We searched the following databases from inception to January 2017: Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We searched registers of ongoing trials and reference lists from relevant studies.
SELECTION CRITERIA
We included randomised controlled trials of insulin-sensitising drugs compared with placebo, no treatment, or an ovulation-induction agent for women with oligo and anovulatory PCOS.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for eligibility and bias. Primary outcomes were live birth rate and gastrointestinal adverse effects. Secondary outcomes included other pregnancy outcomes, menstrual frequency and metabolic effects. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I statistic and reported quality of the evidence for primary outcomes using GRADE methodology.
MAIN RESULTS
We assessed the interventions metformin, clomiphene citrate, metformin plus clomiphene citrate, D-chiro-inositol, rosiglitazone and pioglitazone. We compared these with each other, placebo or no treatment. We included 48 studies (4451 women), 42 of which investigated metformin (4024 women). Evidence quality ranged from very low to moderate. Limitations were risk of bias (poor reporting of methodology and incomplete outcome data), imprecision and inconsistency. Metformin versus placebo or no treatmentThe evidence suggests that metformin may improve live birth rates compared with placebo (OR 1.59, 95% CI 1.00 to 2.51, 4 studies, 435 women, I = 0%, low-quality evidence). The metformin group experienced more gastrointestinal side effects (OR 4.76, 95% CI 3.06 to 7.41, 7 studies, 670 women, I = 61%, moderate-quality evidence) but had higher rates of clinical pregnancy (OR 1.93, 95% CI 1.42 to 2.64, 9 studies, 1027 women, I = 43%, moderate-quality evidence), ovulation (OR 2.55, 95% CI 1.81 to 3.59, 14 studies, 701 women, I = 58%, moderate-quality evidence) and menstrual frequency (OR 1.72, 95% CI 1.14 to 2.61, 7 studies, 427 women, I = 54%, low-quality evidence). There was no clear evidence of a difference in miscarriage rates (OR 1.08, 95% CI 0.50 to 2.35, 4 studies, 748 women, I = 0%, low-quality evidence). Metformin plus clomiphene citrate versus clomiphene citrate alone There was no conclusive evidence of a difference between the groups in live birth rates (OR 1.21, 95% CI 0.92 to 1.59, 9 studies, 1079 women, I = 20%, low-quality evidence), but gastrointestinal side effects were more common with combined therapy (OR 3.97, 95% CI 2.59 to 6.08, 3 studies, 591 women, I = 47%, moderate-quality evidence). However, the combined therapy group had higher rates of clinical pregnancy (OR 1.59, 95% CI 1.27 to 1.99, 16 studies, 1529 women, I = 33%, moderate-quality evidence) and ovulation (OR 1.57, 95% CI 1.28 to 1.92, 21 studies, 1624 women, I = 64%, moderate-quality evidence). There was a statistically significant difference in miscarriage rate per woman, with higher rates in the combined therapy group (OR 1.59, 95% CI 1.03 to 2.46, 9 studies, 1096 women, I = 0%, low-quality evidence) but this is of uncertain clinical significance due to low-quality evidence, and no clear difference between groups when we analysed miscarriage per pregnancy (OR 1.30, 95% CI 0.80 to 2.12, 8 studies; 400 pregnancies, I = 0%, low-quality evidence). Metformin versus clomiphene citrateWhen all studies were combined, findings for live birth were inconclusive and inconsistent (OR 0.71, 95% CI 0.49 to 1.01, 5 studies, 741 women, I = 86%, very low-quality evidence). In subgroup analysis by obesity status, obese women had a lower birth rate in the metformin group (OR 0.30, 95% CI 0.17 to 0.52, 2 studies, 500 women, I = 0%, very low-quality evidence), while data from the non-obese group showed a possible benefit from metformin, with high heterogeneity (OR 1.71, 95% CI 1.00 to 2.94, 3 studies, 241 women, I = 78%, very low-quality evidence). Similarly, among obese women taking metformin there were lower rates of clinical pregnancy (OR 0.34, 95% CI 0.21 to 0.55, 2 studies, 500 women, I = 0%, very low-quality evidence) and ovulation (OR 0.29, 95% CI 0.20 to 0.43 2 studies, 500 women, I = 0%, low-quality evidence) while among non-obese women, the metformin group had more pregnancies (OR 1.56, 95% CI 1.05 to 2.33, 5 studies, 490 women, I = 41%, very low-quality evidence) and no clear difference in ovulation rates (OR 0.81, 95% CI 0.51 to 1.28, 4 studies, 312 women, low-quality evidence, I=0%). There was no clear evidence of a difference in miscarriage rates (overall: OR 0.92, 95% CI 0.50 to 1.67, 5 studies, 741 women, I = 52%, very low-quality evidence). D-chiro-inositol (2 studies), rosiglitazone (1 study) or pioglitazone (1 study) versus placebo or no treatmentWe were unable to draw conclusions regarding other insulin-sensitising drugs as no studies reported primary outcomes.
AUTHORS' CONCLUSIONS
Our updated review suggests that metformin alone may be beneficial over placebo for live birth, although the evidence quality was low. When metformin was compared with clomiphene citrate, data for live birth were inconclusive, and our findings were limited by lack of evidence. Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. An improvement in clinical pregnancy and ovulation suggests that clomiphene citrate remains preferable to metformin for ovulation induction in obese women with PCOS.An improved clinical pregnancy and ovulation rate with metformin and clomiphene citrate versus clomiphene citrate alone suggests that combined therapy may be useful although we do not know whether this translates into increased live births. Women taking metformin alone or with combined therapy should be advised that there is no evidence of increased miscarriages, but gastrointestinal side effects are more likely.
Topics: Abortion, Spontaneous; Anovulation; Clomiphene; Female; Humans; Hypoglycemic Agents; Infertility, Female; Inositol; Insulin Resistance; Live Birth; Metformin; Ovulation Induction; Pioglitazone; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Rosiglitazone; Thiazolidinediones
PubMed: 29183107
DOI: 10.1002/14651858.CD003053.pub6 -
Archives of Gynecology and Obstetrics Mar 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose... (Meta-Analysis)
Meta-Analysis
PURPOSE
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose of this study is to evaluate whether PPOS is as effective as conventional protocols (without GnRHa downregulation).
METHOD
Search terms included "medroxyprogesterone", "dydrogesterone", "progestin-primed ovarian stimulation", "PPOS", "oocyte retrieval", "in vitro fertilization", "IVF", "ICSI", "ART", and "reproductive". The selection criteria were nonrandomized studies and randomized controlled studies. For data collection and analysis, the Review Manager software, Newcastle-Ottowa Quality Assessment Scale and GRADE approach were used.
RESULTS
The clinical pregnancy rates were not significantly different in either RCTs or NRCTs [RR 0.96, 95% CI (0.69-1.33), I = 71%, P = 0.81]; [RR 0.99, 95% CI (0.83-1.17), I = 38%, P = 0.88]. The live birth rates of RCTs and NRCTs did not differ [RCT: RR 1.08, 95% CI (0.74, 1.57), I = 66%, P = 0.69; NRCT: OR 1.03 95% CI 0.84-1.26), I = 50%, P = 0.79]. The PPOS protocol had a lower rate of OHSS [RR 0.52, 95% CI (0.36-0.75), I = 0%, P = 0.0006]. The secondary results showed that compared to the control protocol, the endometrium was thicker [95% CI (0.00-0.78), I = 0%, P = 0.05], the number of obtained embryos was higher [95% CI (0.04-0.65), I = 17%, P = 0.03] and more hMG was needed [in NRCT: 95% CI (307.44, 572.73), I = 0%, P < 0.00001] with the PPOS protocol.
CONCLUSION
The PPOS protocol produces more obtained embryos and a thicker endometrium than the control protocol, with a lower rate of OHSS and an equal live birth rate. The PPOS protocol could be a safe option as a personalized protocol for infertile patients.
TRIAL REGISTRATION
Registration at PROSPERO: CRD42020176577.
Topics: Dydrogesterone; Female; Fertilization in Vitro; Humans; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Reproduction
PubMed: 33433705
DOI: 10.1007/s00404-020-05939-y -
Sports (Basel, Switzerland) Jan 2024Maximal strength is a significant factor in achieving peak performance and injury prevention in athletes. In individualization strategies for the efficient development... (Review)
Review
Maximal strength is a significant factor in achieving peak performance and injury prevention in athletes. In individualization strategies for the efficient development of athletes, it is necessary to consider the respective components separately. The purpose of this study was to systematically examine the effects of the different cycle phases on isometric, isokinetic, and dynamic maximum strength. A systematic literature review was conducted; databases were searched from January 1960 to September 2023. The included studies focused on the expression of maximal strength in the earlier follicular phase as well as at least one comparative phase. Of the initial 707 articles identified, 22 met the selection criteria and were included. The studies considered a total of 433 subjects. Our results revealed medium effects (weighted mean standardized mean difference () = 0.60; seven studies) for isometric maximal strength in favor of the late follicular phase, small effects (weighted mean = 0.39; five studies) for isokinetic maximal strength in favor of the ovulation phase, and small effects (weighted mean = 0.14; three studies) for dynamic maximal strength in favor of the late follicular phase. The results indicate that the early follicular phase is unfavorable for all strength classes. Peak performance in isometric strength is seen in the late follicular phase, whereas isokinetic strength peaks during ovulation. Dynamic strength is optimal in the late follicular phase.
PubMed: 38251305
DOI: 10.3390/sports12010031 -
Frontiers in Endocrinology 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions.
METHODS
We searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients.
RESULTS
The clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, < 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, < 0.001, = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, < 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, < 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, < 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, < 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, < 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, = 0.01)].
CONCLUSION
The findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Infertility, Female; Live Birth; Ovarian Reserve; Ovulation Induction; Pregnancy Rate; Progestins; Randomized Controlled Trials as Topic
PubMed: 34531825
DOI: 10.3389/fendo.2021.702558