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Reproductive Biology and Endocrinology... Oct 2023Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence...
METTL3-regulated m6A modification impairs the decidualization of endometrial stromal cells by regulating YTHDF2-mediated degradation of FOXO1 mRNA in endometriosis-related infertility.
BACKGROUND
Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation.
METHODS
We examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A.
RESULTS
The expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein.
CONCLUSIONS
METTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.
Topics: Animals; Female; Humans; Mice; Endometriosis; Epigenesis, Genetic; Forkhead Box Protein O1; Methyltransferases; RNA, Messenger; RNA-Binding Proteins; Stromal Cells; Transcription Factors; Infertility, Female
PubMed: 37891533
DOI: 10.1186/s12958-023-01151-0 -
Frontiers in Global Women's Health 2024Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced...
Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced cardiovascular disease. This led to a large-scale study called the Women's Health Initiative (WHI) that was conducted to show the cardiovascular benefits of HRT. This study was suspended early because of adverse side effects. The USFDA responded by slapping a "black box" warning on all HRT products. USFDA-approved bioidentical HRT formulations are safe and effective. We propose that these formulations have the "black box" warning removed so that doctors feel more confident in prescribing these products for symptoms of menopause and chronic conditions such as cardiovascular health. We propose eliminating the sale of products containing medroxyprogesterone acetate (MPA) because of the increased risk of heart attacks and breast cancers associated with this medication.
PubMed: 38832110
DOI: 10.3389/fgwh.2024.1397123 -
American Journal of Perinatology Dec 2023While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our...
OBJECTIVE
While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our objective was to evaluate the relationship between receipt of DMPA in the immediate postpartum period and postpartum depressive symptoms.
STUDY DESIGN
This retrospective cohort study included all women who received prenatal and postpartum care at academic obstetric clinics affiliated with a tertiary care institution between January 1, 2008 and December 31, 2014. All women were counseled on contraception prior to hospital discharge. DMPA was available in the hospital pharmacy, and its utilization was documented in the electronic health record. The Patient Health Questionnaire 9 (PHQ-9) was used to screen for postpartum depression for all women at all postpartum visits. A score of 10 or greater was categorized as positive. Bivariable and multivariable analyses were used to identify the association between immediate postpartum DMPA use and a positive postpartum depression screen.
RESULTS
Of the 5,073 women who met inclusion criteria, 410 (8.1%) received DMPA prior to hospital discharge. Compared with women who did not receive DMPA, women who received DMPA prior to hospital discharge were younger, more likely to identify as Black race or Latinx ethnicity, and more likely to be publicly insured. Clinical characteristics also differed. Women who received DMPA were more likely to be obese and to have experienced prenatal depressive symptoms, been diagnosed with a hypertensive disorder of pregnancy, delivered preterm, and delivered vaginally. Receipt of immediate postpartum DMPA was not associated with having a positive screen for postpartum depression in bivariable (5.4 vs. 6.0%, = 0.29) or multivariable (adjusted odds ratio 0.94, confidence interval 0.53-1.68) analyses.
CONCLUSION
Receipt of postpartum DMPA is not associated with a positive postpartum PHQ-9 screen. Concerns about precipitating postpartum depression should not preclude the utilization of DMPA as a contraceptive agent.
KEY POINTS
· Contraception is an important issue for obstetricians to address with postpartum patients.. · Concerns have been raised over the relationship between DMPA and depression.. · Our study shows that DMPA is not associated with a positive postpartum depression screen..
Topics: Pregnancy; Infant, Newborn; Humans; Female; Medroxyprogesterone Acetate; Contraceptive Agents, Female; Depression; Depression, Postpartum; Retrospective Studies; Postpartum Period
PubMed: 34775585
DOI: 10.1055/s-0041-1739431 -
Journal of Pediatric and Adolescent... Dec 2023To describe satisfaction with and preference for subcutaneous depot medroxyprogesterone acetate (DMPA-SC), along with adherence and feasibility, in adolescents and young...
STUDY OBJECTIVE
To describe satisfaction with and preference for subcutaneous depot medroxyprogesterone acetate (DMPA-SC), along with adherence and feasibility, in adolescents and young adults (AYAs) METHODS: Survey of a sample of AYA patients who received DMPA-SC prescription and injection RESULTS: Of 108 eligible patients, 34 completed the survey, and 29 respondents received at least 1 DMPA-SC injection. The mean age was 16.9 years. Seventy-nine point three percent used it for gynecologic reasons, 27.6% for gender dysphoria, and 20.7% for contraception (multiple responses allowed); 93.1% were satisfied with DMPA-SC; 78.6% gave DMPA-SC on time; 88.9% reported that giving the injection was easy; 89.7% reported no problems with administration; 89.3% reported no problems obtaining DMPA-SC; and 76.9% plan to continue using DMPA-SC.
CONCLUSION
In this small sample of patients within a children's hospital, the overall experience with DMPA-SC was favorable. Clinicians caring for adolescents should consider including DMPA-SC in counseling when depot medroxyprogesterone acetate (DMPA) is indicated.
Topics: Child; Humans; Female; Young Adult; Adolescent; Medroxyprogesterone Acetate; Contraceptive Agents, Female; Pilot Projects; Injections, Subcutaneous; Self Administration
PubMed: 37354986
DOI: 10.1016/j.jpag.2023.06.005 -
PloS One 2023South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age.
METHODS
We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18-33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing.
RESULTS
There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups- 18-21 years (46%), 22-25 years (42%) and 26-33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18-21 years) more likely to acquire CT (75.9/100 wy) compared to 26-33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26-33 year old group (82.7/100 wy) compared to the 18-21 year olds (8.4/100 wy; p = 0.01).
CONCLUSIONS
Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.
Topics: Male; Humans; Female; Adolescent; Young Adult; Adult; South Africa; Contraceptive Agents; Prevalence; Incidence; Sexually Transmitted Diseases; Chlamydia trachomatis; Trichomonas vaginalis; Neisseria gonorrhoeae; HIV Infections; Chlamydia Infections
PubMed: 37948399
DOI: 10.1371/journal.pone.0294285 -
FP Essentials Mar 2024Short-acting reversible contraceptives (SARCs) are prescribed routinely by primary care clinicians. SARCs are among the most commonly prescribed contraceptive methods...
Short-acting reversible contraceptives (SARCs) are prescribed routinely by primary care clinicians. SARCs are among the most commonly prescribed contraceptive methods and include combined hormonal oral contraceptive pills, the combined hormonal transdermal patch, the combined hormonal vaginal ring, progestin-only pills, and the 3-month depot medroxyprogesterone acetate injection. To ensure safe prescribing and reduce barriers to receiving SARC methods, family physicians should be familiar with two evidence-based national contraceptive guidelines, the (U.S. MEC) and the (U.S. SPR). SARCs have benefits in addition to pregnancy prevention; as such, these methods may be chosen for reasons other than contraception.
Topics: Pregnancy; Female; Humans; Contraceptive Agents; Contraception; Medroxyprogesterone Acetate; Eligibility Determination; Contraceptives, Oral, Hormonal
PubMed: 38498325
DOI: No ID Found -
Frontiers in Endocrinology 2023The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on...
Original delayed-start ovarian stimulation protocol with a gonadotropin-releasing hormone antagonist, medroxyprogesterone acetate, and high-dose gonadotropin for poor responders and patients with poor-quality embryos.
INTRODUCTION
The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on whether it is also effective for patients with poor-quality embryos and low rates of good blastocyst formation. Specifically, the effectiveness of delayed-start gonadotropin-releasing hormone antagonists with progesterone has not been adequately investigated. Therefore, we compared the efficacy of the original delayed-start gonadotropin-releasing hormone antagonist protocol using medroxyprogesterone acetate (MPA) and high-dose gonadotropin in patients with poor ovarian response.
METHODS
Overall, 156 patients with recurrent assisted reproductive technology failure who underwent the original protocol were included. They received cetrorelix acetate (3 mg) and MPA (10 mg) on cycle day 3, and high-dose gonadotropin was initiated on day 11. When the leading follicle reached 14 mm, ganirelix acetate (0.25 mg) was administered until the trigger day. The number of oocytes retrieved, metaphase II (MII) oocytes, two pronuclear (2PN) zygotes, and good blastocysts and live birth rates were compared between the previous (Cycle A) and original (Cycle B) cycles in three groups (Group A, all patients; Group B, poor responders; and Group C, patients with poor-quality embryos).
RESULTS
In Group A (n=156), the number of MII oocytes (3.6 ± 3.3 versus 4.5 ± 3.6), 2PN zygotes (2.8 ± 2.9 versus 3.8 ± 3.1), good blastocysts (0.5 ± 0.9 versus 1.2 ± 1.6), and live birth rates (0.6 versus 24.4) significantly increased in Cycle B. Similar results were obtained in Group B (n=83; 2PN zygotes [1.7 ± 1.7 versus 2.3 ± 1.8], good blastocysts [0.4 ± 0.7 versus 0.9 ± 1.3], live birth rates [0 versus 18.1]) and Group C (n=73; MII oocytes [5.1 ± 3.8 versus 6.6 ± 4.0], 2PN zygotes [4.0 ± 3.4 versus 5.4 ± 3.4], good blastocysts [0.7 ± 1.1 versus 1.6 ± 1.9], and live birth rates [1.4 versus 31.5]).
CONCLUSION
This original protocol increased the number of MII oocytes retrieved, 2PN zygotes, good blastocysts, and live birth rates in both poor responders and in patients with poor-quality embryos.
Topics: Pregnancy; Female; Humans; Medroxyprogesterone Acetate; Pregnancy Rate; Gonadotropins; Gonadotropin-Releasing Hormone; Ovulation Induction; Hormone Antagonists
PubMed: 38027155
DOI: 10.3389/fendo.2023.1277873 -
The Primary Care Companion For CNS... Nov 2023
Topics: Humans; Medroxyprogesterone Acetate; Paraphilic Disorders; Sex Offenses
PubMed: 37976224
DOI: 10.4088/PCC.23cr03558 -
Journal of Women's Health (2002) Jun 2024Choosing a contraceptive method is a pivotal decision for patients, whereas health care professionals (HCPs) face challenges in providing suitable recommendations.... (Review)
Review
Choosing a contraceptive method is a pivotal decision for patients, whereas health care professionals (HCPs) face challenges in providing suitable recommendations. Adverse sexual effects often lead to dissatisfaction and discontinuation of contraceptives, underscoring the importance of thorough counseling and shared decision making between HCPs and patients. This article aims to investigate the relationship between contraceptive methods and female sexual function through a comprehensive review of available literature, emphasizing the importance of considering sexual health in contraceptive prescription and management. A systematic analysis of existing literature, incorporating studies utilizing validated sexual health questionnaires, was conducted to elucidate the intricate interplay between contraceptives and female sexual function. The review encompasses various contraceptive methods, including combined hormonal contraceptives, progestin-only pills, depot medroxyprogesterone acetate, subdermal contraceptive implants, hormonal intrauterine devices, permanent sterilization, and barrier methods. Insights gleaned from the analysis shed light on the impact of these methods on female sexual health. Comprehensive understanding of the effects of contraceptives on female sexual function is crucial for both HCPs and patients. By integrating sexual health considerations into contraceptive surveillance, compliance can be improved, contraceptive efficacy optimized, and the risk of unwanted pregnancies minimized. This review underscores the significance of tailored counseling and shared decision making in contraceptive management, particularly for cisgender women.
PubMed: 38848279
DOI: 10.1089/jwh.2023.0625 -
Diabetes Research and Clinical Practice Mar 2024The effect of MPA on the lipid profile and CVD risk is still controversial; hence, this comprehensive dose-response meta-analysis of randomized controlled trials was... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effect of MPA on the lipid profile and CVD risk is still controversial; hence, this comprehensive dose-response meta-analysis of randomized controlled trials was conducted to assess the effect of MPA on lipid profiles in women.
METHODS
A comprehensive search was conducted in the following databases: Web of Science, Scopus, PubMed/Medline, and Embase, up to October 20, 2023. A random-effects meta-analysis approach based on the DerSimonian and Laird method was used to compute the combined estimates of the intervention's impact on the lipid profile.
RESULTS
35 eligible studies with 58 arms were included in our meta-analyses analysis. Combined effect sizes suggested a significant effect of MPA on total cholesterol (TC) levels (WMD: -3.43 mg/dL, 95 % CI: -5.38 to -1.48, p < 0.001), HDL-C levels (WMD: -3.34 mg/dL, 95 % CI: -3.77 to -2.91, p < 0.001), and triglyceride (TG) levels (WMD: -9.13 mg/dL, 95 % CI: -10.92 to -7.33, p < 0.001). The subgroup meta-analysis revealed a more substantial reduction in TC in studies with dosages > 2.5 mg/day (WMD: -4.10 mg/dL), mean participant age lower than 60 years (WMD: -3.80 mg/dL), mean BMI lower than 25 kg/m (WMD: -5.61 mg/dL), duration of intervention of 12 months or more (WMD: -3.98 mg/dL), and when the baseline TC value was equal to or greater than 200 mg/dL (WMD: -4.13 mg/dL).
CONCLUSIONS
The current meta-analysis showed a statistically significant decrease in TC, TG, and HDL-C levels and a non-significant increase in LDL-C levels after MPA administration in women.
Topics: Humans; Female; Middle Aged; Lipids; Medroxyprogesterone Acetate; Randomized Controlled Trials as Topic; Biometry; Dietary Supplements; Cholesterol, HDL; Triglycerides
PubMed: 38142749
DOI: 10.1016/j.diabres.2023.111073