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Journal of Ovarian Research Jul 2022Numerous studies have indicated that the level of the Anti-Müllerian hormone (AMH), one of the main markers for the ovarian reserve, does not fluctuate throughout a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Numerous studies have indicated that the level of the Anti-Müllerian hormone (AMH), one of the main markers for the ovarian reserve, does not fluctuate throughout a menstrual cycle, while some studies have rejected this finding. The purpose of this systematic and meta-analysis study is to consensus on all contradictory studies that have measured AMH levels throughout the menstrual cycle and to investigate the exact extent of AMH variation in a cycle.
METHODS
The protocol for this meta-analysis was registered at PROSPERO before data extraction. Relevant studies were identified by systematic search in PubMed, ScienceDirect, Embase, Cochrane Library, and Google Scholar with no limitation on publication date. Longitudinal studies which have evaluated AMH levels in the follicular and luteal phases of an unstimulated (natural) menstrual cycle in healthy women without endocrinology or ovarian disorders were included. We used the JBI Critical Appraisal Checklist for assessing the quality of studies found eligible for meta-analysis.
RESULTS
A total of 11 studies involving 733 women with regular menstrual cycles were included. The results showed that the AMH level in the follicular phase was significantly higher than in the luteal phase (95% Cl = 0.11 [0.01 to 0.21]; p < 0.05) and it varies about 11.5% from the luteal phase. The analysis of studies which had also examined the ovulatory phase (n = 380) showed that the serum levels of AMH in the ovulatory phase (about 2.02 ng/ml) did not significantly vary compared to follicular (95% Cl = 0.11 [-0.10 to 0.33]; p = 0.30) and luteal (95% Cl = 0.06 [-0.08 to 0.20]; p = 0.43) phases.
CONCLUSIONS
According to the results of this study, AMH levels differ between follicular and luteal phases which might be due to ovarian response to the gonadotropins. It seems the phase of AMH measurement needs to be considered for interpretation of the serum AMH test.
Topics: Anti-Mullerian Hormone; Female; Follicular Phase; Humans; Luteal Phase; Menstrual Cycle; Ovarian Reserve; Transforming Growth Factor beta
PubMed: 35778760
DOI: 10.1186/s13048-022-01006-z -
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 -
Endocrine Journal Aug 2022Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes menstrual cycle irregularities and infertility. PCOS is diagnosed based on hyperandrogenism,... (Meta-Analysis)
Meta-Analysis
Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes menstrual cycle irregularities and infertility. PCOS is diagnosed based on hyperandrogenism, polycystic ovarian morphology (PCOM), and an-/oligo-ovulation. Upregulation of anti-Müllerian hormone (AMH) in the serum of women with PCOS may be another suitable alternative diagnostic criterion for PCOM. However, previous meta-analyses have reported conflicting results due to the age-dependent decline in serum AMH levels. Therefore, we performed a meta-analysis to evaluate the threshold of AMH for the diagnosis of PCOS in adolescents and women in their early twenties. Fifteen trials were included in this meta-analysis. PCOS is diagnosed with either Rotterdam criteria, NIH, or AE-PCOS. AMH levels were significantly higher in adolescents with PCOS (weighted mean difference, 3.05; 95% confidence interval: 2.09-4.01) than in the control group. The cutoff values of AMH for the diagnosis of adolescent PCOS were 6.1, 6.26, 7.03, 7.11, 7.2, and 7.25 ng/mL in the studies that reported the usefulness of AMH levels. The summary receiver operating characteristic analysis of the diagnostic accuracy demonstrated that the specificity and sensitivity were 81% and 66.3%, respectively. Our meta-analysis demonstrates that AMH may be a useful diagnostic test for adolescent PCOS and, based on the previous studies included in the meta-analysis, its cutoff value was estimated to be 6-7 ng/mL.
Topics: Adolescent; Anti-Mullerian Hormone; Female; Humans; Hyperandrogenism; Infertility; Peptide Hormones; Polycystic Ovary Syndrome; ROC Curve
PubMed: 35675999
DOI: 10.1507/endocrj.EJ22-0081 -
Evidence-based Complementary and... 2022The infertility caused by polycystic ovary syndrome (PCOS) has received considerable attention. Considerable efforts have been made to improve the rates of pregnancy and...
BACKGROUND
The infertility caused by polycystic ovary syndrome (PCOS) has received considerable attention. Considerable efforts have been made to improve the rates of pregnancy and live birth. Cangfu Daotan Decoction (CFDTD) is a classic prescription for treating infertility in obese women. The efficacy of CFDTD in PCOS is controversial.
OBJECTIVE
To evaluate the effectiveness and safety of CFDTD in treating infertility with PCOS.
METHODS
A literature search was performed in the Cochrane Library, PubMed, Embase, the China National Knowledge Infrastructure, the Wanfang Database, the VIP Chinese Biomedical science journal database, and the Chinese BioMedical database from the date of each database establishment to December 2021. Only randomized controlled trials, which were used to evaluate the efficacy of CFDTD in treating subjects with PCOS, were included in the present study. The quality of evidence was assessed using the Cochrane Reviewer Handbook 5.0.0, and meta-analysis was performed using RevMan 5.3.5 software.
RESULTS
Fourteen studies with a total of 1,433 patients were included in this analysis. The present study indicated that CFDTD could significantly improve pregnancy rate (RR = 1.62, 95% CI (1.44, 1.83), < 0.00001), ovulation rate (RR = 1.40, 95% CI (1.25, 1.56), < 0.00001), and estradiol levels (SMD = 0.80, 95% CI (0.03, 1.58), =0.04), while testosterone levels (SMD = -0.92, 95% CI (-1.52, -0.31), =0.003), homeostatic model assessment for insulin resistance (MD = -0.56, 95% CI (-0.99, -0.12), =0.01), total cholesterol levels (MD = -0.60, 95% CI (-0.76, -0.44), < 0.00001), triglyceride levels (MD = -0.48, 95% CI (-0.60, -0.36), < 0.00001), body mass index (MD = -2.96, 95% CI (-3.88, -2.03), < 0.00001), and the incidence of adverse reactions (RR = 0.47, 95% CI (0.34, 0.65), < 0.00001) were significantly reduced.
CONCLUSIONS
Evidence from the meta-analysis suggested that CFDTD appeared to be an effective and relatively safe treatment for PCOS. However, the influence of CFDTD on reproductive hormones, glucose metabolism, and blood lipids should be carefully concluded. Due to the low quality of the methods used in the included randomized controlled trials, further studies are required with larger sample sizes and well-designed models to confirm our findings.
PubMed: 35620410
DOI: 10.1155/2022/4395612 -
Human Reproduction Update Aug 2022Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment-covariate interactions to identify couples who benefit most from a particular treatment.
OBJECTIVE AND RATIONALE
We performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment-covariate interactions for important baseline characteristics in couples undergoing IUI.
SEARCH METHODS
We searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA.
OUTCOMES
Seven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12-1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33-3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05-1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94-1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45-1.96; RR 0.81, 95% CI 0.32-2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when compared to CC (6 RCTs, 2058 women, HR 1.37, 95% CI 1.15-1.63, I2 = 22%). No strong evidence on the treatment-covariate (female age, BMI or primary versus secondary infertility) interactions was found.
WIDER IMPLICATIONS
In couples with unexplained infertility undergoing IUI-OS, gonadotrophins increased the chance of a live birth and reduced the time to conception compared to CC, at the cost of a higher multiple pregnancy rate, when not differentiating strategies on cancellation criteria or the starting dose. The treatment effects did not seem to differ in women of different age, BMI or primary versus secondary infertility. In a modern practice where a lower starting dose and stricter cancellation criteria are in place, effectiveness and safety of different agents seem both acceptable, and therefore intervention availability, cost and patients' preferences should factor in the clinical decision-making. As the evidence for comparisons to letrozole is based on one RCT providing IPD, further RCTs comparing letrozole and other interventions for unexplained infertility are needed.
Topics: Clomiphene; Female; Fertility Agents, Female; Gonadotropins; Humans; Infertility; Infertility, Female; Insemination; Letrozole; Live Birth; Ovulation Induction; Pregnancy; Pregnancy Rate
PubMed: 35587030
DOI: 10.1093/humupd/dmac021 -
Journal of Assisted Reproduction and... Jul 2022Ovarian hyperstimulation syndrome (OHSS) represents a rare but dangerous condition associated with controlled ovarian stimulation (COS) in IVF/ICSI. Over the last... (Meta-Analysis)
Meta-Analysis Review
Algorithm-based individualization methodology of the starting gonadotropin dose in IVF/ICSI and the freeze-all strategy prevent OHSS equally in normal responders: a systematic review and network meta-analysis of the evidence.
PURPOSE
Ovarian hyperstimulation syndrome (OHSS) represents a rare but dangerous condition associated with controlled ovarian stimulation (COS) in IVF/ICSI. Over the last decades, many strategies have been introduced into clinical practice with the objective of preventing this potentially life-threatening condition. Among these, the freeze-all policy has gained great popularity, thanks to improvements in vitrification. Nevertheless, not all clinics have adequate skills in vitrification procedures and patients may be dissatisfied with a longer time to pregnancy.
METHODS
This study is a systematic review and network meta-analysis of randomized controlled trials comparing different strategies of ovarian stimulation in IVF/ICSI cycles (freeze-all policy, algorithm-based individualization of the starting dose, experience-based individualization of the starting dose, standard dose) in terms of reduction of OHSS, in normal responders.
RESULTS
The results indicate that only the algorithm-based individualization of the starting gonadotropin dose reduces OHSS similarly to the freeze-all strategy.
CONCLUSION
Albeit in the era of the freeze-all policy, the personalization of the starting gonadotropin dose obtained by the use of algorithms should be pursued as a valid and safe option for IVF.
Topics: Algorithms; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Network Meta-Analysis; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 35551563
DOI: 10.1007/s10815-022-02503-2 -
Frontiers in Endocrinology 2022Although gonadotropin-releasing hormone (GnRH) agonist has been introduced as a beneficial luteal phase support (LPS), the optimal strategy of GnRH agonist remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although gonadotropin-releasing hormone (GnRH) agonist has been introduced as a beneficial luteal phase support (LPS), the optimal strategy of GnRH agonist remains unclear. This network meta-analysis was therefore performed to determine the comparative efficacy and safety of multiple-dose versus single-dose GnRH agonist protocol for LPS in patients undergoing IVF/ICSI cycles.
METHODS
We searched relevant studies in PubMed, Embase and the Cochrane Registry of Controlled Trials (CENTRAL) from their inception util to September 2021. Live birth, clinical pregnancy rate, multiple pregnancy rate, and clinical abortion rate was evaluated. Pairwise and network meta-analysis were conducted using RevMan and ADDIS based on random-effects model, respectively. Moreover, the prioritization of protocols based on ranking probabilities for different outcomes were performed.
RESULTS
Sixteen RCTs met our eligibility criteria. Pairwise meta-analysis showed that multiple-dose protocol of GnRH agonist was effective for increasing live birth rate (OR 1.80, 95% CI 1.15 to 2.83, =0.01) and clinical pregnancy rate (OR 1.89, 95% CI 1.01 to 3.56, =0.05) as well as decreasing clinical abortion rate (OR 0.55, 95% CI 0.34 to 0.90, =0.02). Meanwhile, single-dose protocol of GnRH agonist was effective for increasing clinical pregnancy rate (OR 1.45, 95% CI 1.11 to 1.89, =0.007) and multiple pregnancy rate (OR 2.55, 95% CI 1.12 to 5.78, =0.03). However, network meta-analysis only confirmed that multiple-dose protocol of GnRH agonist was the best efficacious strategy for live birth rate (OR 2.04, 95% CrI 1.19 to 3.93) and clinical pregnancy rate (OR 2.10, 95% CrI 1.26 to 3.54).
CONCLUSION
Based on the results of NMA, multiple-dose protocol may be the optimal strategy for patients undergoing IVF/ICSI cycles owing to its advantage in increasing live birth and clinical pregnancy rate. Moreover, single-dose protocol may be the optimal strategy for improving multiple pregnancy rate. However, with the limitations, more RCTs are required to confirm our findings.
Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Lipopolysaccharides; Luteal Phase; Network Meta-Analysis; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 35432219
DOI: 10.3389/fendo.2022.802688 -
Evidence-based Complementary and... 2022In this systematic review, the effects of acupuncture combined with moxibustion on reproductive and metabolic outcomes in patients with polycystic ovary syndrome (PCOS)... (Review)
Review
OBJECTIVES
In this systematic review, the effects of acupuncture combined with moxibustion on reproductive and metabolic outcomes in patients with polycystic ovary syndrome (PCOS) were evaluated.
METHODS
Randomized controlled trials (RCTs) assessing acupuncture combined with moxibustion + basic treatment (experimental group) versus basic treatment alone (control group) for treating PCOS were identified from English and Chinese databases up to November 3, 2021. Outcomes related to pregnancy, ovulation, miscarriage, sex hormones, and metabolic disorders were of interest. In the meta-analysis, risk ratios (RRs) and mean differences (MDs) and their 95% confidence intervals (CIs) were used as effect measures.
RESULTS
Twenty-five RCTs ( = 1991) were included. The pooled results showed that the experimental group had significant increases in the pregnancy rate (RR 1.81, 95% CI 1.58 to 2.08) and ovulation rate (RR 1.31, 95% CI 1.22 to 1.40) and decreases in the miscarriage rate (RR 0.45, 95% CI 0.28 to 0.73), and ovarian volume (MD -0.75 cm, 95% CI -1.30 to -0.20). In the experimental group, improvements in the luteinizing hormone (LH) level, the LH-to-follicle-stimulating hormone (FSH) ratio, total testosterone level, fasting insulin level, and body mass index, but not in FSH, oestradiol, or dehydroepiandrosterone sulfate levels, were significantly greater. All reported adverse events were mild. Based on the limitations of risk of bias, inconsistency, imprecision, and/or publication bias, the level of evidence was judged to be moderate for the pregnancy rate, ovulation rate, miscarriage rate, LH level, and LH/FSH ratio and very low for the other outcomes.
CONCLUSION
Among patients with PCOS, using acupuncture combined with moxibustion as a complementary therapy to basic treatments can improve pregnancy, ovulation, and miscarriage rates, the levels some sex hormones, and metabolic indicators, with good safety. Additionally, this combination therapy may have no effect on the FSH, oestradiol, or dehydroepiandrosterone sulfate level.
PubMed: 35399633
DOI: 10.1155/2022/3616036 -
Przeglad Menopauzalny = Menopause Review Mar 2022The paths of medically assisted reproduction represent the most important scientific progress to cope with the inability to achieve spontaneous conception (SC) and to... (Review)
Review
INTRODUCTION
The paths of medically assisted reproduction represent the most important scientific progress to cope with the inability to achieve spontaneous conception (SC) and to reach desired parenthood. Couples undergoing assisted reproductive technology (ART) and couples not facing ovulation induction and artificial fertilization show sufficient levels of well-being and psychological adjustment. However, in some cases couples undergoing ART show lower perceived quality of life than couples with SC.Our aim is to investigate the main psychological variables involved in the special risk condition of medically assisted reproduction and how they could direct specific guidelines to enhance mental wellbeing in dealing with infertility.
MATERIAL AND METHODS
In this regard, we performed a systematic review following the PRISMA guidelines. From all the studies included, the considered outcome measures were psychological, social, and relational variables and are presented in a systematic approach.
RESULTS
A total of 14 studies were included in this article, according to our strict inclusion criteria.
CONCLUSIONS
Conflicting results have been proven by this systematic review. Even though all underlined the importance of taking charge of the psychological variables in infertility, few studies monitored and evaluated the effectiveness of these interventions. Moreover, none of the selected studies monitored the evolutionary implications of parental competence on the development of children born from ART.
PubMed: 35388278
DOI: 10.5114/pm.2022.114404 -
Reproductive Biology and Endocrinology... Apr 2022This systematic review and meta-analysis aimed to compare the short-term reproductive and long-term obstetric outcomes after endometrial preparations by ovarian... (Meta-Analysis)
Meta-Analysis
Systematic review update and meta-analysis of randomized and non-randomized controlled trials of ovarian stimulation versus artificial cycle for endometrial preparation prior to frozen embryo transfer in women with polycystic ovary syndrome.
PURPOSE
This systematic review and meta-analysis aimed to compare the short-term reproductive and long-term obstetric outcomes after endometrial preparations by ovarian stimulation protocols and hormone replacement therapy (HRT) in women with polycystic ovary syndrome (PCOS) prior to frozen embryo transfer (FET).
METHOD
PubMed, EMBASE, Web of Science and the Cochrane Library were searched to identify relevant studies. Primary outcome was live birth rate, secondary outcomes included the rates of clinical pregnancy, miscarriage, implantation and hCG-postive, cycle cancellation, ectopic pregnancy, preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus and abnormal placentation.
RESULTS
Nine studies, including 8327 patients with PCOS, were identified. Live birth rate was significantly higher (RR = 1.11, 95% CI = 1.03-1.19) and miscarriage rate (RR = 0.60, 95% CI = 0.46-0.78) was significantly lower in stimulated protocol compared to the rates in HRT. While the rates of ongoing pregnancy, clinical pregnancy, implantation, hCG-positive, cycle cancellation and ectopic pregnancy showed no significant difference between the two protocols. Compared HRT with different stimulation protocols, significantly higher clinical pregnancy rate (RR = 1.54, 95% CI = 1.20-1.98) were found in letrozole group, but not in the other subgroups. For the obstetric outcomes, the preterm birth and preeclampsia rates were significantly lower in the stimulated group compared to that in the HRT group (RR = 0.85, 95% CI = 0.74-0.98; RR = 0.57, 95% CI = 0.40-0.82, respectively), while gestational hypertension, gestational diabetes mellitus and abnormal placentation rates showed no significant difference.
CONCLUSIONS
The present data suggest that ovarian stimulation protocol as an endometrial preparation regimen prior to FET might be superior to HRT protocol with a significantly higher rate of live birth, lower risk of miscarriage, preterm birth and preeclampsia. Our study showed stimulated protocol is better than HRT regimen as an endometrial preparation for women with PCOS. However, quality of the evidence is low, more well-designed RCT studies are still needed to confirm the results before clinical recommendation, particularly direct comparisons between letrozole and other stimulated regimens.
Topics: Controlled Clinical Trials as Topic; Embryo Transfer; Female; Humans; Infant, Newborn; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Premature Birth
PubMed: 35366912
DOI: 10.1186/s12958-022-00931-4