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AIDS Research and Human Retroviruses Jan 2022Phosphorylating enzymes (PEs) are responsible for activating nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) such as tenofovir (TFV) and are critical for...
Phosphorylating enzymes (PEs) are responsible for activating nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) such as tenofovir (TFV) and are critical for their conversion to obtain intracellular antiviral activity. However, there are limited data available regarding the expression of PEs and their activity in the female genital tract. This work compared the messenger RNA (mRNA) expression levels of PEs in human female genital tissue, immune cells, and animal models that are commonly used in human immunodeficiency virus (HIV) research. Furthermore, the effect of contraceptive hormones and proinflammatory cytokines on tenofovir diphosphate (TFV-DP) formation and efficacy in human vaginal, epithelial, and immune cells was also evaluated. We found that human vaginal and ectocervical tissues had similar mRNA expression for seven PEs tested. Polymerase chain reaction results revealed that creatine kinase brain (CKB), mitochondrial creatine kinase 1 (CKMT1), mitochondrial creatine kinase 2 (CKMT2), adenylate kinase AK3L1 (AK4), and nucleoside diphosphate kinase 1 (NME1) exhibited a 10- to 10,000-fold higher expression level in a vaginal epithelial cell line, VK2, compared with CD4 T cells ( < .05). Medroxyprogesterone acetate (MPA)/progesterone (P4) and IL-1β/IL-8 treatment resulted in altered TFV-DP levels in VK2 and PM1 cells. MPA and P4 at concentrations above 0.1 μM, as well as IL-1β and IL-8 at concentrations above 10 ng/mL, significantly decreased HIV-1 inhibition in PM1 cells when 1 μM TFV was added. However, this observed effect of hormones and cytokines was abrogated when TFV concentration was raised to 1 mM. These results elucidate the role of PEs in TFV metabolism and provide information regarding differences in PE tissue expression for animal models commonly used in HIV testing. This information can be applied to better understand and interpret data obtained using these models.
Topics: Animals; Anti-HIV Agents; Creatine Kinase, Mitochondrial Form; Female; HIV Infections; HIV-1; Humans; Medroxyprogesterone Acetate; Tenofovir
PubMed: 33567990
DOI: 10.1089/AID.2020.0250 -
Journal of the International AIDS... Jan 2018HIV affects more women than any other life-threatening infectious agent, and most infections are sexually transmitted. HIV must breach the female genital tract mucosal...
INTRODUCTION
HIV affects more women than any other life-threatening infectious agent, and most infections are sexually transmitted. HIV must breach the female genital tract mucosal barrier to establish systemic infection, and clinical studies indicate virus more easily evades this barrier in women using depot-medroxyprogesterone acetate (DMPA) and other injectable progestins for contraception. Identifying a potential mechanism for this association, we learned DMPA promotes susceptibility of wild-type mice to genital herpes simplex virus type 2 (HSV-2) infection by reducing genital tissue expression of the cell-cell adhesion molecule desmoglein-1 (DSG-1) and increasing genital mucosal permeability. Conversely, DMPA-mediated increases in genital mucosal permeability and HSV-2 susceptibility were eliminated in mice concomitantly administered exogenous oestrogen (E). To confirm and extend these findings, herein we used humanized mice to define effects of systemic DMPA and intravaginal (ivag) E administration on susceptibility to genital infection with cell-associated HIV-1.
METHODS
Effects of DMPA or an intravaginal (ivag) E cream on engraftment of NOD-scid-IL-2Rgc (NSG) mice with human peripheral blood mononuclear cells (hPBMCs) were defined with flow cytometry. Confocal microscopy was used to evaluate effects of DMPA, DMPA and E cream, or DMPA and the pharmacologically active component of the cream on vaginal tissue DSG-1 expression and genital mucosal permeability to low molecular weight (LMW) molecules and hPBMCs. In other studies, hPBMC-engrafted NSG mice (hPBMC-NSG) received DMPA or DMPA and ivag E cream before genital inoculation with 10 HIV-1-infected hPBMCs. Mice were euthanized 10 days after infection, and plasma HIV-1 load quantified by qRT-PCR and splenocytes used to detect HIV-1 p24 antigen via immunohistochemistry and infectious virus via TZM-bl luciferase assay.
RESULTS
Whereas hPBMC engraftment was unaffected by DMPA or E treatment, mice administered DMPA and E (cream or the pharmacologically active cream component) displayed greater vaginal tissue expression of DSG-1 protein and decreased vaginal mucosal permeability to LMW molecules and hPBMCs versus DMPA-treated mice. DMPA-treated hPBMC-NSG mice were also uniformly susceptible to genital transmission of cell-associated HIV-1, while no animal concomitantly administered DMPA and E cream acquired systemic HIV-1 infection.
CONCLUSION
Exogenous E administration reduces susceptibility of DMPA-treated humanized mice to genital HIV-1 infection.
Topics: Animals; Estrogens; Female; HIV Infections; HIV-1; Humans; Medroxyprogesterone Acetate; Mice; Mice, Inbred NOD; Vagina
PubMed: 29334191
DOI: 10.1002/jia2.25063 -
Alternative Therapies in Health and... Jul 2023The high resistance rate and high recurrence rate of progesterone only as a treatment for endometrial cancer (EC) limit its clinical application. Metformin (MET) may...
CONTEXT
The high resistance rate and high recurrence rate of progesterone only as a treatment for endometrial cancer (EC) limit its clinical application. Metformin (MET) may have antitumor ability. Combining MET and medroxyprogesterone acetate (MPA) may strengthen their inhibitory effects on proliferation of EC cells, but MET's mechanisms remain unclear.
OBJECTIVE
The study intended to identify the specific molecular mechanism that MET combined with MPA uses against EC progression.
DESIGN
The research team performed a controlled animal study.
SETTING
The study took place at Xuzhou Medical University in Xuzhou, China.
ANIMALS
The animals were16 female non-obese diabetic-severe combined immunodeficient (NOD-SCID) nude mice, about 12 to 16 g in weight.
INTERVENTIONS
The research team divided randomly, the mice into four groups and induced EC in all groups, four in each group: (1) The control group which received received normal saline, (2) the MPA group, which received 100 mg/kg of MPA; (3) the MET group, which received metformin at the rate of 200 mg/kg, each gavage volume was 0.1ml; (4) the MET+MPA group, which received 100 mg/kg of MPA and 200 mg/kg of MET.
OUTCOME MEASURES
The research team: (1) used a CCK-8 kit, an EdU assay, and a flow-cytometry assay to measure cancer-cell proliferation, count, and viability; determine the cell cycle; and measure apoptosis; (2) performed a Western blot analysis to determine the expression of the PR, CD133, pAkt, totalAkt, p-mTOR, and totalTOR antibodies; and (3) determined the size and volume of tumors in vivo and used immunohistochemical staining to determine expression of the Ki67 protein.
RESULTS
The MET+MPA group had a significantly lower number of cancer cells than the MET or MDA groups (both P < .001). That group also had significantly more stagnated cancer cells in the G0/G1 phase and significantly fewer cancer cells in the S phase or G2/M phase control, MET, or MPA groups (all P < .01). The MET+MPA group's PCNA and Ki-67 protein expression was significantly lower than that of the MET and MPA group. The EDU assay yielded similar results. Additionally, the MET+MPA group had significantly higher PR expression than that of to MET or MPA group (both P < .001). The MET and MPA groups' expression of CD133, p-Akt, and p-mTOR were significantly lower than those of the control group, while the MET+MPA group's levels were significantly lower than those of the MET and MPA groups. In-vivo experiments revealed that the MET and MPA groups did show decreased tumor size and volume. The MET+MPA group had tumor weights that were significantly lower and tumor volumes were significantly smaller than those of the MET and MPA groups (all P < .001). Immunohistochemical analysis revealed that the MET+MPA group's levels of the Ki-67 antigen were significantly lower than those of the MET and MPA groups.
CONCLUSIONS
MET inhibited the proliferation of EC cells by increasing MPA-sensitivity, which was dependent on the inhibition of the CD133 expression and the Akt/mTOR pathway. In addition, if MET acts as an effective progestin sensitizer, it certainly offers promising therapeutic prospects for patients with early-stage EC or overgrown endometrium who have fertility requirements.
Topics: Humans; Female; Animals; Mice; Medroxyprogesterone Acetate; Metformin; Mice, Nude; Proto-Oncogene Proteins c-akt; Receptors, Progesterone; Mice, Inbred NOD; Mice, SCID; Endometrial Neoplasms; Cell Proliferation; TOR Serine-Threonine Kinases; Apoptosis; Cell Line, Tumor
PubMed: 37171945
DOI: No ID Found -
Frontiers in Immunology 2020Depot Medroxyprogesterone (DMPA) is one of the most widely used contraceptives in Sub-Saharan Africa where HIV incidence is high. We explored the effect of DMPA on the...
BACKGROUND
Depot Medroxyprogesterone (DMPA) is one of the most widely used contraceptives in Sub-Saharan Africa where HIV incidence is high. We explored the effect of DMPA on the activation of HIV cellular targets and inflammation as a possible mechanism of increased HIV risk with DMPA use. Since sex work is known to affect the immune system, this study aimed to understand the effect of DMPA on the immune system among sex workers and non-sex worker women.
METHODS
Twenty-seven DMPA-using HIV seronegative female sex workers (FSW) and 30 DMPA-using HIV seronegative non-sex worker (SW) women were enrolled in the study. Twenty-four FSWs and 30 non-sex workers who were not using any hormonal contraception (no HC) were recruited as controls. Blood and cervico-vaginal samples were collected from all participants and assayed for T cell activation and proinflammatory cytokines.
RESULTS
Among no HC users, sex workers had lower expression of CD38 and CD69 on blood-derived CD4 T cells along with lower CD4CCR5 cells frequency in the endocervix. Plasma MCP-1, TNFα and IL-17 also had reduced expression in FSW not using HC. Non-sex workers using DMPA had elevated proportions of blood-derived CD4CD38, CD4CD69 and CD4HLA-DR T cells relative to non-sex workers who were not taking any HC. DMPA-using non-sex workers also had an increased level of plasma interferon gamma (IFN-), monokine induced by interferon- (MIG) and sCD40L, alongside higher proportion of CD4CD38 and CD4CD69 T cells at the cervix compared to non-sex workers no-HC controls., Finally, non-sex workers and FSWs using DMPA had similar levels of genital and peripheral CD4 T cell activation and inflammation.
CONCLUSION
DMPA increased inflammation and expression of activation markers on potential HIV target cells in non-sex workers. These data show that DMPA is a strong immune modulator and its use counteracts the decreased immune activation associated with sex work. These findings suggest that inflammation and increased HIV target cells in blood and at the genital tract may be mechanisms by which DMPA increases susceptibility to HIV.
Topics: Adolescent; Adult; Biomarkers; CD4-Positive T-Lymphocytes; Contraceptive Agents; Cytokines; Female; Humans; Immunophenotyping; Inflammation; Kenya; Lymphocyte Activation; Medroxyprogesterone; Mucous Membrane; Public Health Surveillance; Sex Workers; Young Adult
PubMed: 33717049
DOI: 10.3389/fimmu.2020.598307 -
The Cochrane Database of Systematic... Jul 2015Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated... (Review)
Review
BACKGROUND
Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life.
OBJECTIVES
We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women.
SEARCH METHODS
Through June 2015, we searched for observational studies. The databases included PubMed, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports.
SELECTION CRITERIA
We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis.
MAIN RESULTS
We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use.
AUTHORS' CONCLUSIONS
Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.
Topics: Age Factors; Case-Control Studies; Cohort Studies; Contraceptives, Oral, Hormonal; Female; Fractures, Bone; Humans; Intrauterine Devices, Medicated; Medroxyprogesterone Acetate; Observational Studies as Topic; Progestins; Time Factors
PubMed: 26195091
DOI: 10.1002/14651858.CD009849.pub3 -
The Journal of Adolescent Health :... Feb 2019Adolescents may encounter many barriers to initiating contraception. 'Quick Start' is a recommended approach for initiating contraception on the same day as a provider...
PURPOSE
Adolescents may encounter many barriers to initiating contraception. 'Quick Start' is a recommended approach for initiating contraception on the same day as a provider visit. We examined factors associated with health care provider attitudes and practices related to 'Quick Start' provision of combined hormonal contraception (CHC) and depot medroxyprogesterone acetate (DMPA) to adolescents.
METHODS
We analyzed weighted survey data from providers in publicly funded health centers and from office-based physicians (n = 2,056). Using multivariable logistic regression, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of the associations between provider characteristics and frequent (very often or often vs. not often or never) 'Quick Start' provision of CHC and DMPA to adolescents in the past year.
RESULTS
The prevalence of considering 'Quick Start' as safe was high for CHC (public-sector providers [87.5%]; office-based physicians [80.2%]) and DMPA (public-sector providers [80.9%]; office-based physicians [78.8%]). However, the prevalence of frequent 'Quick Start' provision was lower, particularly among office-based physicians (CHC: public-sector providers [74.2%]; office-based physicians [45.2%]; DMPA: public-sector providers [71.4%]; office-based physicians [46.9%]). Providers who considered 'Quick Start' unsafe or were uncertain about its safety had lower odds of frequent 'Quick Start' provision compared with those who considered it safe (public-sector providers: CHC aOR = 0.09 95% CI 0.06-0.13, DMPA aOR = 0.07 95% CI 0.05-0.10; office-based physicians: CHC aOR = 0.06 95% CI 0.02-0.22, DMPA aOR = 0.07 95% CI 0.02-0.20).
CONCLUSIONS
While most providers reported that 'Quick Start' initiation of CHC and DMPA among adolescents is safe, fewer providers reported frequent 'Quick Start' provision in this population, particularly among office-based physicians.
Topics: Adolescent; Attitude of Health Personnel; Contraceptive Agents, Hormonal; Female; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Male; Medroxyprogesterone Acetate; Pregnancy; Pregnancy in Adolescence; Surveys and Questionnaires
PubMed: 30392865
DOI: 10.1016/j.jadohealth.2018.08.012 -
PloS One 2023Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan... (Randomized Controlled Trial)
Randomized Controlled Trial
Misreporting contraceptive use and the association of peak study progestin levels with weight and BMI among women randomized to the progestin-only injectable contraceptives DMPA-IM and NET-EN.
Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan Africa. Insufficient robust data on their relative side-effects and serum concentrations limit understanding of reported outcomes in contraception trials. The WHICH clinical trial randomized HIV-negative women to DMPA-IM (n = 262) or norethisterone enanthate (NET-EN) (n = 259) at two South African sites between 2018-2019. We measured serum concentrations of study and non-study progestins at initiation (D0) and peak serum levels, one week after the 24-week injection [25 weeks (25W)], (n = 435) and investigated associations between study progestin levels, and BMI and weight of participants. Peak median serum concentrations were 6.59 (IQR 4.80; 8.70) nM for medroxyprogesterone (MPA) (n = 161) and 13.6 (IQR 9.01; 19.0) nM for norethisterone (NET) (n = 155). MPA was the most commonly quantifiable non-study progestin at D0 in both arms (54%) and at 25W in the NET-EN arm (27%), followed by NET at D0 in both arms (29%) and at 25W in the DMPA-IM arm (19%). Levonorgestrel was quantifiable in both arms [D0 (6.9%); 25W (3.4%)], while other progestins were quantifiable in ≤ 14 participants. Significant negative time-varying associations were detected between MPA and NET concentrations and weight and BMI in both contraceptive arms and a significant increase was detected for peak serum progestin concentrations for normal weight versus obese women. Contraceptive-related reported outcomes are likely confounded by MPA, more so than NET, with reported DMPA-IM effects likely underestimated, at sites where DMPA-IM is widely used, due to misreporting of contraceptive use before and during trials, and 'tail' effects of DMPA-IM use more than six months before trial enrolment. Peak serum levels of MPA and NET are negatively associated with BMI and weight, suggesting another source of variability between trial outcomes and a potential increase in side-effects for normal weight versus overweight and obese women. Trail registration: The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).
Topics: Female; Humans; Progestins; Medroxyprogesterone Acetate; Contraceptive Agents; Body Mass Index; Norethindrone; Obesity
PubMed: 38134043
DOI: 10.1371/journal.pone.0295959 -
Frontiers in Endocrinology 2021To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor...
OBJECTIVE
To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR).
PATIENTS AND METHODS
This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates.
RESULTS
In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% 29.6%, P=0.14).
CONCLUSION
For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.
Topics: Adult; Contraceptives, Oral, Hormonal; Dydrogesterone; Female; Fertilization in Vitro; Follow-Up Studies; Humans; Infertility, Female; Medroxyprogesterone; Oocyte Retrieval; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Outcome; Progestins; Prognosis; Retrospective Studies
PubMed: 34630325
DOI: 10.3389/fendo.2021.708704 -
Contraception Dec 2015Use of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely... (Review)
Review
BACKGROUND
Use of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely to result in ectopic pregnancies than some other methods such as combined hormonal and barrier contraceptives.
OBJECTIVE
To describe ectopic pregnancy risk associated with use of implants and progestin-only injectable contraceptives through a systematic review of published studies.
DATA SOURCES
We searched electronic databases for articles in any language published through May 2015 describing studies of progestin-only injectables and implants. We also searched bibliographies and review articles for additional studies.
STUDY SELECTION AND EXTRACTION
Studies that reported any pregnancies were included in the review. Independent data extraction was performed by two authors based on predefined data fields, and where possible, we calculated the proportion of pregnancies that were ectopic and the ectopic pregnancy incidence rate per 1000 woman-years.
RESULTS
Fifty-three studies of implants and 28 studies of injectables were identified; 79% reported pregnancy location. The proportion of ectopic pregnancy ranged from 0 to 100% with an incidence of 0-2.9 per 1000 woman-years in studies of marketed levonorgestrel implants. Studies of etonogestrel implants and the injectables, depot-medroxyprogesterone acetate and norethisterone enanthate, reported few ectopic pregnancies.
CONCLUSION
Progestin-only contraceptive implants and injectables protect against ectopic pregnancy by being highly effective in preventing pregnancy overall; however, the absolute risk of ectopic pregnancy varies by type of progestin. Risk of ectopic pregnancy should not be a deterrent for use or provision of these methods.
Topics: Contraception; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Incidence; Injections; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Pregnancy; Pregnancy, Ectopic; Progestins
PubMed: 26363431
DOI: 10.1016/j.contraception.2015.08.016 -
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