Korean medicines for poor ovarian reserve in infertility: A protocol for a multicenter observational study.
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ABSTRACT: Introduction
Many infertile patients have used Korean medicines (KMs) as a primary or adjuvant therapeutic method to improve in vitro fertilization success rates. The aim of this multicenter observational study is to investigate the effects of KMs on poor ovarian reserve (POR) in infertile patients.Methods and analysis
We will perform a prospective multicenter observational study. This study will recruit 50 women between 25 and 44 years of age with infertility caused by POR from among patients who visit the KM clinic. All participants will visit the KM clinic on the 2nd or 3rd day of menstruation to receive the KMs. KM treatment will be delivered for 3 menstrual cycles (3 months) and will include herbal decoction, acupuncture, or moxibustion on demand. Every participant will be assessed based on KM clinical symptoms, a quality of life questionnaire, and ovarian reserve test results.Ethics and dissemination
The study was approved by Institutional Review Board of Semyung University (SMU-IM-190501). The results will be published in a peer-reviewed journal and will be disseminated electronically and in print.Trial registration number
Clinical Research Information Service: KCT0004209.
SUBMITTER: Choi TY
PROVIDER: S-EPMC6946327 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Korean medicines for poor ovarian reserve in infertility: A protocol for a multicenter observational study.
Choi Tae-Young TY Jun Ji Hee JH Lee Hye Won HW Ang Lin L Kim Eun Seop ES Go Ho Yeon HY You Sooseong S Lee Myeong Soo MS
Medicine 20191101 44
<h4>Introduction</h4>Many infertile patients have used Korean medicines (KMs) as a primary or adjuvant therapeutic method to improve in vitro fertilization success rates. The aim of this multicenter observational study is to investigate the effects of KMs on poor ovarian reserve (POR) in infertile patients.<h4>Methods and analysis</h4>We will perform a prospective multicenter observational study. This study will recruit 50 women between 25 and 44 years of age with infertility caused by POR from ...[more]
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Project description:BackgroundOvarian reserve is the number of oocytes remaining in the ovary and is one of the most important aspects of a woman's reproductive potential. Research on the association between thyroid dysfunction and ovarian reserve has yielded controversial results. In our study, we aimed to investigate the relationship between thyroid-stimulating hormone (TSH) levels and ovarian reserve markers.MethodsFrom 1443 women seeking infertility care, the data of 1396 women aged between 20-45 years old who had a body mass index between 18-30 kg/m2 were recruited for this retrospective study. The anti-Müllerian hormone (AMH) and TSH relationship was analyzed with generalized linear and polynomial regression.ResultsMedian age, follicle-stimulating hormone (FSH), AMH, and TSH levels were 36.79 years, 9.55 IU/L, 3.57 pmol/L, and 1.80 mIU/L, respectively. Differences between TSH groups were statistically significant in terms of AMH level, antral follicle count (AFC), and age (p = 0.007 and p = 0.038, respectively). A generalized linear regression model could not explain age-matched TSH levels concerning AMH levels (p > 0.05). TSH levels were utilized in polynomial regression models of AMH, and the 2nd degree was found to have the best fit. The inflection point of the model was 2.88 mIU/L.ConclusionsOur study shows a correlation between TSH and AMH values in a population of infertile women. Our results are as follows: a TSH value of 2.88 mIU/L yields the highest AMH result. It was also found that AMH and AFC were positively correlated, while AMH and FSH were negatively correlated.
| S-EPMC10625203 | biostudies-literature
Project description:INTRODUCTION:BRCA1/2 gene mutations increase risk of breast and/or ovarian cancer and may have implications for reproductive health. Indirect biomarkers of the ovarian primordial follicle pool (anti-Müllerian hormone (AMH)) and one small study in female cadavers suggest that ovarian reserve may be reduced in BRCA mutation carriers, but findings are conflicting and association between circulating AMH and primordial follicle number is not established. The aim of this study is to measure primordial follicle density in premenopausal ovarian tissue samples from women with BRCA1/2 gene mutations versus age-matched comparison group. METHODS AND ANALYSIS:Prospective observational study measuring associations between BRCA gene mutation status, premenopausal ovarian primordial follicle density and serum AMH concentrations versus age-matched premenopausal women from the general population. Primordial follicle density will be measured in cortical sections from ovarian tissue collected at the time of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in 88 BRCA1 gene mutation carriers, 65 BRCA2 gene mutation carriers and 157 non-mutation carriers. Primordial follicle density will be determined by counting follicles in a known volume of ovarian cortical tissue using light microscopy. Follicles will be identified by immunohistochemical staining for oocyte marker mouse vasa homologue. To inform the mechanisms underlying reduced ovarian reserve, the proportion of follicles containing oocytes with DNA damage will be determined by immunohistochemical staining for phosphorylated histone H2AX and terminal deoxynucleotidyl transferase dUTP nick end labelling assay to identify apoptotic cells. Follicle density will be correlated with circulating AMH concentrations quantified in the same cohort, using an electrochemiluminescence immunoassay on an automated platform. ETHICS AND DISSEMINATION:Ethics approval has been granted by Peter MacCallum Cancer Centre to access biobanks, including; The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab-HREC#97_27) and the What Happens after Menopause? (HREC12PMCC24-12/90) and Melbourne IVF.
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Project description:Follicular fluid (FF) molecules, and their increase or decrease, can contribute to appropriate follicular growth and oocyte maturation, thus being related to female infertility conditions. In this paper, we studied the changes and the relationships of some biochemical components, hormones, antioxidant enzymes, F2-Isoprostanes (F2-IsoPs), and resolvin (Rv) D1 in the FF of infertile women with different reproductive conditions such as endometriosis, reduced ovarian reserve, and idiopathic infertility during assisted reproductive techniques (ART). In the whole population, positive correlations between albumin (ALB)/iron (Fe), ALB/beta-2-microglobulin (B2MG), and F2-IsoPs/RvD1 were detected in the FF. In FF from aged women, increased levels of follicle stimulating hormone (FSH) and reduced anti-Müllerian hormone (AMH) levels were associated with a worse oocyte quality. The negative ART outcome was influenced by patient age and AMH, B2MG, and FSH levels. Moreover, the reduced ovarian reserve condition was characterised by a significant decrease in oocyte number and quality, AMH amount, and lactate dehydrogenase (LDH) activity, as well as by an increase in age and FSH levels. In the presence of endometriosis, high levels of MDA and RvD1 were detected in FF, with a decrease in luteinising hormone (LH). Finally, among the molecules examined, none characterised the condition of idiopathic infertility. These data could support the identification of new FF markers in different reproductive disorders, suggesting the need for personalised therapeutic approaches and optimised ART outcomes. In particular, the evaluation of resolvins and lipid mediators in FF could be a promising field of investigation with which to understand the entity of oxidative stress and inflammation in some female infertility conditions.
| S-EPMC9916781 | biostudies-literature
Project description:Study questionAre urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting?Summary answerHigher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care.What is known alreadyExperimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown.Study design, size, durationWe examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study.Participants/materials, setting, methodsWe quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking.Main results and the role of chanceWe observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated.Limitations, reasons for cautionWe demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals.Wider implications of the findingsEnvironmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development.Study funding/competing interestsWork supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.
| S-EPMC4677966 | biostudies-literature
Project description:BackgroundMounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian reserve in young, infertile women.MethodsOur study included 2276 Korean women who attended a single fertility center in 2016-2018. Women's exposure to air pollution was assessed using concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting.ResultsThe mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM10 was associated with decrease in AMH ratio among total population (β= -0.06, 95% confidence interval: -0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM2.5 were associated with 3% (95% CI: -0.07, 0.00) and 10% (95% CI: -0.18, -0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents.ConclusionsIn a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women's fertility.
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Project description:BackgroundNewborn ovary homeobox (NOBOX) gene plays a critical role in the transcriptional regulation of oocyte-specific genes. Previous studies have demonstrated a pathogenic effect of NOBOX variants on premature ovarian insufficiency (POI) patients. Poor ovarian response (POR) is a risk factor for POI. Therefore, genetic variants in the NOBOX gene may also be studied as risk factors for POR development.AimsThe aim of the study is to investigate the association between seven known NOBOX single-nucleotide polymorphisms (SNPs) and POR in Jordanian females.Settings and designThis was a case-control study of 60 females with POR for controlled ovarian hyperstimulation and 59 healthy females with no history of reproductive problems. Blood samples were collected from the participants and seven SNPs of NOBOX gene were screened.Subjects and methodsDNA was extracted from blood samples. Polymerase chain reaction with primers specific for seven known SNPs in NOBOX gene was used to amplify the specified region within the gene followed by Sanger sequencing.ResultsThe seven SNPs investigated in this study, namely, rs77587352 (c.271G>T, p. Gly91Trp), rs7800847 (c.349C>T, p. Arg117Trp), rs193303102 (c.907C>T, p. Arg303X), rs193303103 (c.1025G>C, p. Ser342Thr), rs193303104 (c.1048G>T, p. Val350Leu), rs201947677 (c.1064G>A, p. Arg355His), and rs146227301 (c.1856C>T, p. Pro619Leu), only represent the wild-type allele in both females with POR and healthy participants.ConclusionsThe results show that only monomorphic genotype of the NOBOX variants was found in Jordanian females studied.
| S-EPMC6594122 | biostudies-literature
Project description:Importance:Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. Objective:To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. Design, Setting, and Participants:Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N?=?981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Exposures:Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. Main Outcomes and Measures:The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. Results:A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n?=?84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n?=?579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n?=?83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n?=?654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n?=?69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n?=?737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and Relevance:Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.
| S-EPMC5744252 | biostudies-literature
Project description:BACKGROUND:While overt thyroid disease is a well known risk factor for infertility, the potential consequences of mild thyroid dysfunction or thyroid autoimmunity remain unknown. Experimental studies suggest a considerable role for thyroid hormone in the physiological mechanisms of ovarian reserve, but translation of such findings to human studies remains rare. A potential role for thyroid function in female reproduction could be especially relevant when the cause of infertility remains unknown, such as in women with diminished ovarian reserve (DOR) or unexplained infertility. The aims of this study were to investigate the association of thyroid function and autoimmunity with markers of ovarian reserve day 3 follicle-stimulating hormone (FSH) concentrations and antral follicle count (AFC), and to investigate whether thyroid function or autoimmunity may have different effects in women with DOR or unexplained infertility. METHODS:Thyrotropin, free thyroxine, thyroxine, free triiodothyronine (fT3), triiodothyronine, thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs), as well as AFC and the day 3 FSH concentration, were measured among women seeking fertility treatment at the Massachusetts General Hospital Fertility Center. Multiple linear or mixed regression models were used to study the association of thyroid function or autoimmunity with AFC or day 3 FSH. RESULTS:In the total study population (436 women, 530 AFC measurements), there was no association of thyroid function or TPOAb positivity with AFC. However, TgAb positivity was associated with a higher AFC (mean difference = 3.4 [95% confidence interval (CI) 1.8-5.1], p < 0.001). In women with DOR or unexplained infertility, lower fT3 and TPOAb positivity were associated with a lower AFC (fT3: continuous nonlinear association, p = 0.009; TPOAb positivity: -2.3 follicles [confidence interval -3.8 to -0.5], p = 0.01), while TgAb positivity was not associated with AFC. Neither thyroid function nor thyroid antibody positivity was associated with the day 3 FSH concentration. CONCLUSIONS:This study found that lower fT3 and TPOAb positivity are associated with a lower AFC in women with DOR or unexplained infertility. Future studies are required to replicate these findings and further elucidate the role of TgAbs and underlying mechanisms through which thyroid function and autoimmunity is associated with ovarian reserve.
| S-EPMC6157366 | biostudies-literature
Project description:BackgroundEffective methods for the treatment of reproductive dysfunction are limited. Previous studies have reported that acupuncture can modulate female hormone levels, improve menstrual disorders, alleviate depression and improve pregnancy rates. However, studies of acupuncture for diminished ovarian reserve (DOR) are lacking.ObjectiveTo carry out a prospective observational study aimed at assessing the effect of EA on the reproductive hormone levels of patients with DOR seeking fertility support and consider its safety.MethodsEligible patients with DOR received EA for 12 weeks: five times a week for 4 weeks followed by three times a week for 8 weeks. The primary outcome was the change in mean follicle-stimulating hormone (FSH) level at week 12. Mean luteinising hormone (LH) and serum oestradiol (E2) levels, FSH/LH ratios and symptom scale scores were simultaneously observed.ResultsTwenty-one patients with DOR were included in the final analysis. Mean FSH levels fell from 19.33±9.47 mIU/mL at baseline to 10.58±6.34 mIU/mL at week 12 and 11.25±6.68 mIU/mL at week 24. Change in mean FSH from baseline was -8.75±11.13 mIU/mL at week 12 (p=0.002) and -8.08±9.56 mIU/mL at week 24 (p=0.001). Mean E2 and LH levels, FSH/LH ratios and irritability scores were improved at weeks 12 and/or 24. Approximately 30% patients reported subjective increases in menstrual volume after treatment.ConclusionsEA may modulate reproductive hormone levels and the effects seem to persist for at least 12 weeks after treatment with no significant side effects. EA may improve the ovarian reserve of patients with DOR, though further research is needed.Trial registration numberNCT02229604; Results.
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Project description:BackgroundThis study was conducted to demonstrate the effectiveness and safety of herbal medicine and acupuncture treatment in unexplained infertile females.MethodsOne hundred patients were recruited from 3 Korean Medicine hospitals in Korea and they voluntarily signed informed consent agreements. Participants took the Onkyeong-tang (120cc) twice daily between menstrual cycle day (MCD) 3 and 12, and herbal medicine for ovulation and implantation (120cc) twice daily between MCD 13 and 28. They also received acupuncture and moxibustion treatment during 4 menstrual cycles. After the 4 menstrual cycle treatment period, there were 3 menstrual cycle observation periods. The primary outcome is signified by clinical pregnancy rates (CPR) and the secondary outcomes were implantation rates (IR), ongoing pregnancy rates (OPR), and live birth rates.Results90 patients completed the study. 13 of the 90 subjects became pregnant. The CPR and IR was 14.44%. 7 of 13 pregnant subjects had continuing pregnancy for over 12 weeks, so that the OPR was 53.85%. The birth rate was 7.78%. All 7 pregnant patients gave birth to their babies and all the babies were live singletons and healthy. There were no serious adverse events.ConclusionsThe findings of this study may provide the possibility of effectiveness and safety of Korea medicine treatment for unexplained infertile women. Further study is required due to lack of control and small sample size in this study.
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