Association between Leukemia Inhibitory Factor Gene Polymorphism and Clinical Outcomes among Young Women with Poor Ovarian Response to Assisted Reproductive Technology.
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ABSTRACT: Background
Does the presence of single-nucleotide polymorphisms (SNPs) in the leukemia inhibitory factor (LIF) gene affect ovarian response in infertile young women?Methods
This was a case-control study recruiting 1744 infertile women between January 2014 to December 2015. The 1084 eligible patients were stratified into four groups using the POSEIDON criteria. The gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR), anti-Müllerian hormone (AMH), and LIF SNP genotypes were compared among the groups. The distributions of LIF and FSHR among younger and older patients were compared. Clinical outcomes were also compared.Results
The four groups of poor responders had different distributions of SNP in LIF. The prevalence of LIF genotypes among young poor ovarian responders differed from those of normal responders. Genetic model analyses in infertile young women revealed that the TG or GG genotype in the LIF resulted in fewer oocytes retrieved and fewer mature oocytes relative to the TT genotypes. In older women, the FSHR SNP genotype contributed to fewer numbers of mature oocytes.Conclusions
LIF and FSHR SNP genotypes were associated with a statistically significant reduction in ovarian response to controlled ovarian hyperstimulation in younger and older women with an adequate ovarian reserve, respectively.
SUBMITTER: Liu YL
PROVIDER: S-EPMC9917712 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Association between Leukemia Inhibitory Factor Gene Polymorphism and Clinical Outcomes among Young Women with Poor Ovarian Response to Assisted Reproductive Technology.
Liu Yung-Liang YL Lee Chun-I CI Liu Chung-Hsien CH Cheng En-Hui EH Yang Shun-Fa SF Tsai Hsueh-Yu HY Lee Maw-Sheng MS Lee Tsung-Hsien TH
Journal of clinical medicine 20230119 3
<h4>Background</h4>Does the presence of single-nucleotide polymorphisms (SNPs) in the leukemia inhibitory factor (LIF) gene affect ovarian response in infertile young women?<h4>Methods</h4>This was a case-control study recruiting 1744 infertile women between January 2014 to December 2015. The 1084 eligible patients were stratified into four groups using the POSEIDON criteria. The gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR), anti-Müllerian hormone ...[more]
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Project description:Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light-dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer's and Parkinson's disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.
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Project description:Study questionDo women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART?Summary answerWithout correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses.What is known alreadyStudies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor.Study design, size, durationA population-based cohort consisting of all women registered in the Medical Birth Registry of Norway as having given birth between 1 January 1984 and 31 December 2010 was assembled (n = 812 986). Cancers were identified by linkage to the Cancer Registry of Norway. Study subjects were followed from start of first pregnancy during the observational period until the first cancer, death, emigration, or 31 December 2010.Participants/materials, setting, methodsOf the total study population (n = 806 248), 16 525 gave birth to a child following ART. Cox regression analysis computed hazard ratios (HR) and 95% confidence intervals (CI) comparing cancer risk between ART women and non-ART women; for overall cancer, and for cervical, ovarian, uterine, central nervous system (CNS), colorectal and thyroid cancers, and for malignant melanoma.Main results and the role of chanceA total of 22 282 cohort members were diagnosed with cancer, of which 338 were ART women and 21 944 non-ART women. The results showed an elevated risk in one out of seven sites for ART women. The HR for cancer of the CNS was 1.50 (95% CI 1.03- 2.18), and among those specifically subjected to IVF (without ICSI) the HR was 1.83 (95% CI 1.22-2.73). Analysis of risk of overall cancer gave an HR of 1.16 (95% CI 1.04-1.29). Among those who had delivered only one child by the end of follow-up, the HR for ovarian cancer was 2.00 (95% CI 1.08-3.65), and for those nulliparous at entry the HR was 1.80 (95% CI 1.04-3.11). However, all findings became non-significant after correcting for multiple analyses.Limitations, reasons for cautionThe results of elevated risk of overall cancer and CNS cancer lost significance when adjusting for multiple analyses, implying an important limitation of the study. The follow-up time was relatively short, especially for ART women. In addition, as the cohort was relatively young, there were few incident cancers, especially for some rarer cancer forms, such as uterine cancer. Risk assessments according to different causes of infertility could not be done.Wider implications of the findingsIn light of the findings in the present study, further studies should be made on risk of CNS and ovarian cancer, and continued monitoring of all those treated with ART is encouraged. Our findings may only be generalizable to women who give birth after ART, and the risk for women who remain nulliparous after ART remains to be assessed.Study funding/competing interestThe study was funded by the Norwegian National Advisory Unit on Women's Health. All authors claim no competing interests.
| S-EPMC4507330 | biostudies-literature
Project description:IntroductionInfertility affects 15% of women of reproductive age in the United States. The use of assisted reproductive technology (ART) has been rising globally, as well as a growing recognition of reproductive factors that increase risk for cardiovascular disease (CVD).Areas coveredWomen with infertility who use ART are more likely to have established CVD risk factors, such as obesity, dyslipidemia, hypertension, and diabetes. They are also more likely to experience adverse pregnancy outcomes, which are associated with both peripartum and long-term cardiovascular complications. ART may lead to increased cardiometabolic demands due to ovarian stimulation, pregnancy itself, and higher rates of multifetal gestation. Preeclampsia risk appears greater with frozen rather than fresh embryo transfers.Expert opinionThe use of ART and its association with long term CVD has not been well-studied. Future prospective and mechanistic studies investigating the association of ART and CVD risk may help determine causality. Nevertheless, CVD risk screening is critical pre-pregnancy and during pregnancy to reduce pregnancy complications that elevate future CVD risk. This also offers a window of opportunity to connect patients to longitudinal care for early management of cardiometabolic risk profile and initiation of preventive lifestyle and pharmacotherapy interventions tailored toward patient-specific risk factors.
| S-EPMC10615881 | biostudies-literature
Project description:ObjectiveTo evaluate the effects of different ovarian stimulation protocols on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile women with adenomyosis.MethodsWe carried out a retrospective cohort study among infertile women with adenomyosis receiving IVF/ICSI treatment, including 257 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles. In fresh ET cycles, ultra-long, long, short, and antagonist protocols were adopted. In FET cycles, patients received long-acting GnRH agonist (GnRHa) pretreatment or not. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes included implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR).ResultsIn fresh ET cycles, compared with ultra-long and long protocols, IR (49.7%, 52.1% versus 28.2%, P=0.001) and CPR (64.3%, 57.4% versus 35.6%, P=0.004) significantly decreased in the short protocol. Similarly, compared with ultra-long and long protocols, a decreased inclination of IR (49.7%, 52.1% versus 33.3%) and CPR (57.4%, 64.3% versus 38.2%) existed in the antagonist protocol, although no statistical significance was detected because of strict P adjustment of Bonferroni method (Padj=0.008). Compared with long protocol, LBR in short protocol decreased obviously (48.2% versus 20.3%, P<0.001). In FET cycles, no matter which origin of embryos, there were no statistical differences in IR, CPR, and LBR. For women ≥35 years receiving fresh ET, CPR was higher in ultra-long and long protocols (52.1%, 50.0% versus 20.0%, 27.5%, P=0.031) compared to antagonist and short protocols. For women ≥35 years receiving FET, compared with ultra-long and antagonist protocols, cycles with embryos originating from long and short protocols had higher proportions of long-acting GnRHa pretreatment (30.4%,30.00 versus 63.9%, 51.4%, P=0.009). IR (61.1%, 48.6% versus 32.6%, 25.0%, P=0.020) and CPR (58.3%, 48.6% versus 30.4%, 25.0%, P=0.024) in long and short protocols were higher than rates of ultra-long and antagonist protocols, but no statistical differences were supported because of strict Bonferroni method (Padj=0.008).ConclusionIn infertile women with adenomyosis, if a fresh embryo was planned for transfer, an ultra-long or long protocol might be beneficial. If antagonist and short protocols were used, whole embryos frozen followed by FET was recommended. In FET cycles, embryos derived from different protocols had no impact on pregnancy outcomes.
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Project description:The study aimed to investigate if assisted reproductive technology (ART) treatment or a diagnosis of infertility were associated with the risk of ovarian cancer or borderline ovarian tumors (BOT) in parous women. In a population-based register study of 1,340,097 women with a first live birth in Sweden 1982-2012, the relationship between ART treatments, infertility and incidence of ovarian cancer or BOT were investigated using Cox regression analysis. In the cohort, 38,025 women gave birth following ART, 49,208 following an infertility diagnosis but no ART and 1,252,864 without infertility diagnosis or ART. During follow-up, 991 women were diagnosed with ovarian cancer and 747 with BOT. Women who gave birth following ART had higher incidence of both ovarian cancer (adjusted hazard ratio [aHR] 2.43, 95% confidence interval [CI] 1.73-3.42) and BOT (aHR 1.91, 95% CI 1.27-2.86), compared to women without infertility. Compared to women with infertility diagnoses and non-ART births, women with ART births also had a higher incidence of ovarian cancer (aHR 1.79, 95% CI 1.18-2.71) and BOT (aHR 1.48, 95% CI 0.90-2.44). Our results suggest that women who have gone through ART have a higher risk of ovarian cancer and BOT. At least part of that risk seems to be due to the underlying infertility and not the treatment per se, since the increased risk was smaller when comparing to other infertile women. As ART treatments are becoming more common and ovarian cancer usually occur in women of advanced age, larger studies with longer follow-up are needed in order to confirm or refute our findings.
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Project description:Background: Thyroid dysfunction is prevalent in reproductive-age women and has been identified as a risk factor for female infertility. However, it remains largely unclear whether subtle thyroid dysfunction, as estimated by moderately high thyrotropin (TSH) levels within the normal range, is associated with ovarian reserve in infertile women before assisted reproductive technology (ART) treatment. Methods: This cross-sectional study involved 3501 euthyroid infertile women, including 2189 women with TSH levels ≤2.5 μIU/mL and 1312 women with high-normal TSH levels (2.51-4.20 μIU/mL). Ovarian reserve markers were compared between women with low- and high-normal TSH levels. Correlation analysis and regression models were used to estimate the association of TSH levels with ovarian reserve. In addition, the association of subtle thyroid dysfunction with ovarian reserve was further evaluated after stratification for different infertility diagnoses and statuses of thyroid autoimmunity (TAI). Results: In the total population, women with high-normal TSH levels had significantly decreased anti-Müllerian hormone (AMH) concentrations (p < 0.001), a lower bilateral antral follicle count (AFC) (p < 0.001), and a higher prevalence of diminished ovarian reserve (DOR) (p = 0.018) than women with low-normal TSH levels. The TSH levels showed a negative association with both AMH levels (r = -0.050, p = 0.003) and bilateral AFC (r = -0.071, p < 0.001). Furthermore, the association of high-normal TSH levels with decreased AMH and AFC was more prominent in infertile women with ovulation dysfunction (p = 0.002, p = 0.002), unexplained infertility (p = 0.020, p = 0.028), or negative TAI (both p < 0.001). Conclusions: These data suggested that subtle thyroid dysfunction was associated with DOR in infertile women before ART treatment, which will add evidence that strengthens the systematic screening of TSH levels/TAI in infertile women and will contribute to the discussion of specific TSH cutoff values in predicting ovarian reserve.
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Project description:PurposePolycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients.MethodsIn this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes.ResultsAccording to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates.ConclusionAST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients' GCs.Trial registrationClincialTrials.gov Identifier: NCT03991286.
| S-EPMC9050983 | biostudies-literature
Project description:BackgroundLong-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.MethodsThis nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided.ResultsAfter a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time.ConclusionsIncreased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.
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Project description:ObjectiveTo study the relation of dietary phytoestrogens intake and clinical outcomes of women undergoing infertility treatment with the use of assisted reproductive technology (ART).DesignProspective cohort study.SettingFertility center.Patient(s)A total of 315 women who collectively underwent 520 ART cycles from 2007 to 2013.Intervention(s)None.Main outcome measure(s)Implantation, clinical pregnancy, and live birth rates per initiated cycle.Result(s)Soy isoflavones intake was positively related to live birth rates in ART. Compared with women who did not consume soy isoflavones, the multivariable-adjusted odds ratios of live birth (95% confidence interval) for women in increasing categories of soy isoflavones intake were 1.32 (0.76-2.27) for women consuming 0.54-2.63 mg/d, 1.87 (1.12-3.14) for women consuming 2.64-7.55 mg/d, and 1.77 (1.03-3.03) for women consuming 7.56-27.89 mg/d.Conclusion(s)Dietary soy intake was positively related to the probability of having a live birth during infertility treatment with ART.
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Project description:STUDY QUESTION:Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER:Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY:Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION:A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS:All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE:The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children. LIMITATIONS, REASONS FOR CAUTION:Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare. WIDER IMPLICATIONS OF THE FINDINGS:Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests.
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