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Human Reproduction Update Jul 2024The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of exercise, diet and/or pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity: a systematic review and network meta-analysis.
BACKGROUND
The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic-pituitary-ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population.
OBJECTIVE AND RATIONALE
This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity.
SEARCH METHODS
A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS.
OUTCOMES
Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) -2.61 kg/m2; 95% CI -3.04 to -2.19; τ2 = 0.22) and adding exercise (MD -2.35 kg/m2; 95% CI -2.81 to -1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94-26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67-13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) -2.91; 95% CI -4.07 to -1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99-3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD -1.59; 95% CI -3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above.
WIDER IMPLICATIONS
Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process.
Topics: Adult; Female; Humans; Body Mass Index; Diet; Exercise; Network Meta-Analysis; Obesity; Overweight; Ovulation
PubMed: 38627233
DOI: 10.1093/humupd/dmae008 -
Clinical and Experimental Reproductive... Apr 2024Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among reproductive-age women. As a leading cause of anovulatory infertility, it complicates...
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among reproductive-age women. As a leading cause of anovulatory infertility, it complicates fertility treatments, including in vitro fertilization. The widely accepted 2003 Rotterdam diagnostic criteria for PCOS include sub-phenotypes based on variations in androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. In this systematic review, we examined the impacts of inositol and vitamin D on fertility in PCOS. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we used relevant keywords to comprehensively search databases including PubMed, Google Scholar, and MDPI. From an initial pool of 345 articles, 10 met the inclusion criteria. The articles suggest that vitamin D and inositol, particularly myo-inositol and D-chiro-inositol, may represent therapeutic options for PCOS. Vitamin D influences ovarian follicular development, glucose regulation, and insulin sensitivity. When combined with metformin therapy, it is associated with improved menstrual regularity and ovulation. Inositol is crucial for cellular signaling, energy metabolism, glucose regulation, and fertility. This systematic review underscores the importance of investigating inositol and vitamin D within a PCOS management strategy, given the disorder's prevalence and impacts on fertility and metabolic health. Although these agents show promise, additional research could clarify their mechanisms of action and therapeutic benefits. This review emphasizes the need for exploration of effective treatments to improve the quality of life among individuals with PCOS. Inositol and vitamin D represent potential options, but more studies are required to elucidate their roles in the management of this condition.
PubMed: 38599886
DOI: 10.5653/cerm.2023.06485 -
Archives of Gynecology and Obstetrics Jun 2024The effect of platelet-rich plasma (PRP) on ovarian reserve markers in poor ovarian response (POR) is challenging. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The effect of platelet-rich plasma (PRP) on ovarian reserve markers in poor ovarian response (POR) is challenging.
AIM
This systematic review and meta-analysis was, therefore, designed to evaluate the effectiveness of intra-ovarian injection of autologous PRP on improving ovarian reserve markers and assisted reproductive technology (ART) outcomes in infertile women with POR.
METHODS
A systematic search was conducted for the efficacy of intra-ovarian injection of autologous PRP on the improvement of ovarian reserve markers and ART outcomes in infertile women with POR. The methodological quality of the included studies was checked and eligible studies were included in the meta-analysis to find pooled results. Keywords were primary ovarian insufficiency, premature menopause, poor responder, poor ovarian response, diminished/decreased ovarian reserve, platelet-rich plasma, and intra-ovarian or a combination of them. The effect of PRP on fertility indices was evaluated using the standardized mean difference (SMD). The analysis was performed through STATA version 13.
KEY RESULTS
13 studies containing 1289 patients were included. Mean age, body mass index (BMI) and duration of infertility was 37.63 ± 2.66 years, 24 ± 1.23 kg/m and 4.79 ± 1.64 years, respectively. Most of the studies measured the outcomes 2-3/3 months after intra-ovarian injection of autologous PRP. The antral follicular count (AFC) after treatment by PRP is higher with an SMD of 0.95 compared to before treatment. The day 3 follicle-stimulating hormone (FSH) after treatment by PRP is lower with an SMD of - 0.25 compared to before treatment. The day 3 estradiol (E2) after treatment by PRP is higher with an SMD of 0.17 compared to before treatment. The anti-Mullerian hormone (AMH) after treatment by PRP is higher with an SMD of 0.44 compared to before treatment. The total oocytes number after treatment by PRP is higher with an SMD of 0.73 compared to before treatment. The number of MII oocytes after treatment by PRP is higher with an SMD of 0.63 compared to before treatment. The number of cleavage-stage embryos after treatment by PRP is higher with an SMD of 1.31 compared to before treatment. The number of day 5 embryo after treatment by PRP is higher with an SMD of 1.28 compared to before treatment. Pooled estimation of a meta-analysis of prevalence studies reported a prevalence of 22% for clinical pregnancy, 5% for spontaneous pregnancy and 21% for ongoing pregnancy following PRP therapy.
CONCLUSION
Intra-ovarian injection of PRP improved ovarian reserve markers with increasing AFC, serum level of AMH and day 3 E2 and decreasing serum level of day 3 FSH. In addition, this treatment improved ART outcomes through the increasing of number total oocytes, number of MII oocytes, number of cleavage-stage embryos and number of day 5 embryos in POR women.
IMPLICATIONS
Although treatment of POR women remains challenging, the use of intra-ovarian injection of autologous PRP in POR patients prior to IVF/ICSI cycles is a sign of new hope for increasing the success of IVF/ICSI. However, further well-organized, randomized controlled trials should be conducted to substantiate this result and recommend intra-ovarian injection of PRP as part of routine treatment in women with POR.
Topics: Humans; Platelet-Rich Plasma; Female; Ovarian Reserve; Infertility, Female; Ovulation Induction; Pregnancy; Ovary; Pregnancy Rate; Treatment Outcome; Injections; Anti-Mullerian Hormone; Reproductive Techniques, Assisted
PubMed: 38589612
DOI: 10.1007/s00404-024-07442-0 -
Phytotherapy Research : PTR Jun 2024The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well... (Review)
Review
The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.
Topics: Crocus; Humans; Female; Plant Extracts; Premenstrual Syndrome; Animals; Carotenoids; Polycystic Ovary Syndrome; Menopause; Dysmenorrhea; Phytochemicals; Vitamin A; Cyclohexenes; Glucosides; Terpenes
PubMed: 38558480
DOI: 10.1002/ptr.8186 -
Journal of Ovarian Research Mar 2024Follitropin delta is a novel recombinant follicle stimulating hormone preparation uniquely expressed in a human fetal retinal cell line by recombinant DNA technology. To... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Follitropin delta is a novel recombinant follicle stimulating hormone preparation uniquely expressed in a human fetal retinal cell line by recombinant DNA technology. To date, no systematic review was available about the safety and the efficacy of the follitropin delta. The objective of this study was systematically reviewing the available literature and to provide updated evidence regarding the efficacy-safety profile of follitropin delta when compared to other gonadotropin formulations for ovarian stimulation in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles.
METHODS
An extensive search was performed to identify phase 1, phase 2 and phase 3 RCTs in humans focused on follitropin delta use for ovarian stimulation in IVF/ICSI cycles. The risk of bias and the overall quality of the evidence was analyzed. All data were extracted and analyzed using the intention-to-treat principle and expressed per woman randomized.
RESULTS
A total of 7 RCTs (1 phase 1 RCT, 2 phase 2 RCTs and 4 phase 3 RCTs) were included in the qualitative analysis, whereas data of three phase 3 RCTs were meta-analyzed. All trials compared personalized recombinant follitropin delta treatment versus conventional recombinant follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. No difference between two regimens was detected for clinical pregnancy rate [odds ratio (OR) 1.06; 95% confidence intervals (CI): 0.90, 1.24; P = 0.49; I = 26%], ongoing pregnancy rate (OR 1.15; 95%CI: 0.90, 1.46; P = 0.27; I = 40%), and live birth rate (OR 1.18; 95%CI: 0.89, 1.55; P = 0.25; I = 55%). No data were available regarding cumulative success rates. The rate of adoption of strategies to prevent ovarian hyperstimulation syndrome (OHSS) development (OR 0.45; 95%CI: 0.30, 0.66; P < 0.0001; I = 0%), and the rate of both early OHSS (OR 0.62; 95%CI: 0.43, 0.88; P = 0.008; I = 0%) and all forms of OHSS (OR 0.61; 95%CI: 0.44, 0.84; P = 0.003; I = 0%) were significantly lower in the group of patients treated with personalized follitropin delta treatment compared to those treated with conventional follitropin alfa/beta administration.
CONCLUSION
Personalized follitropin delta treatment is associated with a lower risk of OHSS compared to conventional follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. The absence of cumulative data does not allow definitive conclusions to be drawn regarding the comparison of the effectiveness of the two treatments.
PROTOCOL STUDY REGISTRATION
CRD42023470352 (available at http://www.crd.york.ac.uk/PROSPERO ).
Topics: Female; Humans; Male; Pregnancy; Fertilization in Vitro; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Semen; Sperm Injections, Intracytoplasmic; Randomized Controlled Trials as Topic
PubMed: 38486276
DOI: 10.1186/s13048-024-01372-w -
Journal of Medical Internet Research Feb 2024Emerging digital health technology has moved into the reproductive health market for female individuals. In the past, mobile health apps have been used to monitor the...
BACKGROUND
Emerging digital health technology has moved into the reproductive health market for female individuals. In the past, mobile health apps have been used to monitor the menstrual cycle using manual entry. New technological trends involve the use of wearable devices to track fertility by assessing physiological changes such as temperature, heart rate, and respiratory rate.
OBJECTIVE
The primary aims of this study are to review the types of wearables that have been developed and evaluated for menstrual cycle tracking and to examine whether they may detect changes in the menstrual cycle in female individuals. Another aim is to review whether these devices are effective for tracking various stages in the menstrual cycle including ovulation and menstruation. Finally, the secondary aim is to assess whether the studies have validated their findings by reporting accuracy and sensitivity.
METHODS
A review of PubMed or MEDLINE was undertaken to evaluate wearable devices for their effectiveness in predicting fertility and differentiating between the different stages of the menstrual cycle.
RESULTS
Fertility cycle-tracking wearables include devices that can be worn on the wrists, on the fingers, intravaginally, and inside the ear. Wearable devices hold promise for predicting different stages of the menstrual cycle including the fertile window and may be used by female individuals as part of their reproductive health. Most devices had high accuracy for detecting fertility and were able to differentiate between the luteal phase (early and late), fertile window, and menstruation by assessing changes in heart rate, heart rate variability, temperature, and respiratory rate.
CONCLUSIONS
More research is needed to evaluate consumer perspectives on reproductive technology for monitoring fertility, and ethical issues around the privacy of digital data need to be addressed. Additionally, there is also a need for more studies to validate and confirm this research, given its scarcity, especially in relation to changes in respiratory rate as a proxy for reproductive cycle staging.
Topics: Female; Humans; Fertility; Heart Rate; Menstrual Cycle; Menstruation; Reproductive Health; Wearable Electronic Devices
PubMed: 38358798
DOI: 10.2196/45139 -
Journal of Assisted Reproduction and... Apr 2024A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian... (Meta-Analysis)
Meta-Analysis Review
Basal characteristics of patients who responded to Ovarian Fragmentation for Follicular Activation (OFFA) or In Vitro Activation (IVA): a systematic review and meta-analysis.
A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.
Topics: Humans; Female; Ovarian Follicle; Pregnancy; Pregnancy Rate; Ovulation Induction; Fertilization in Vitro; Live Birth; Primary Ovarian Insufficiency; Follicle Stimulating Hormone
PubMed: 38315420
DOI: 10.1007/s10815-024-03046-4 -
BMC Pregnancy and Childbirth Jan 2024To assess the value of intraovarian PRP in women with low ovarian reserve. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the value of intraovarian PRP in women with low ovarian reserve.
SEARCH STRATEGY
Screening of databases from inception to January 2023 using the keywords related to "Platelet-rich plasma" AND "poor ovarian reserve" OR "ovarian failure".
SELECTION CRITERIA
Fourteen studies (1632 participants) were included, 10 included women with POR, 1 included women with POI and 3 included both POR and POI women.
DATA COLLECTION AND ANALYSIS
Extracted data included study settings, design, sample size, population characteristics, volume, timing and preparation of PRP administration, and outcome parameters.
MAIN RESULTS
AMH level was evaluated in 11 studies (2099 women). The mean difference (MD) was 0.09 with 95% CI of - 0.06, 0.24 (P = 0.25). Antral follicular count level was assessed in 6 studies (1399 women). The MD was 1.73 with 95% CI of 0.81, 2.66 (P < 0.001). The number of oocytes retrieved was evaluated in 7 studies (1413 women). The MD was 1.21 with 95% CI of 0.48, 1.94 (P = 0.001).
CONCLUSION
This systematic review found a significant improvement of AFC, the number of retrieved oocytes, the number of cleavage embryos and the cancellation rate in women with POR.
TRIAL REGISTRATION
Registration number CRD42022365682.
Topics: Female; Humans; Ovarian Reserve; Ovulation Induction; Ovarian Diseases; Primary Ovarian Insufficiency; Platelet-Rich Plasma
PubMed: 38280991
DOI: 10.1186/s12884-024-06251-2 -
Hormones (Athens, Greece) Jan 2024To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic... (Review)
Review
Effects of letrozole alone or in combination with gonadotropins on ovulation induction and clinical pregnancy in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS).
METHODS
Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS).
RESULTS
Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome.
CONCLUSION
Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.
PubMed: 38280115
DOI: 10.1007/s42000-024-00531-4 -
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