2 recent studies largely dispel concern about the restoration of fertility after discontinuation of injectable contraceptives. After cessation of use of depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate there is some delay in fertility restoration, but fertility is not impaired once the progestogen is cleared from the body. Pharmacokinetic data suggest that norethisterone enanthate exerts less of an inhibitory effect on the hypothalamic-pituitary-ovarian system than DMPA, so that ovulation returns earlier after discontinuation of the former injectable. There appears to be no significant difference between nulligravid and parous women in the return of fertility, indicating that use of injectable contraceptives does not need to be restricted to women who have completed their families. In Pardthaisong's study of over 1000 Thai women, the median delay until conception after contraceptive discontinuation was 3 months among oral contraceptive users, 4.5 months for the IUD, and 5.5 months for DMPA users. 36 months after discontinuation, only 6.4% of the 796 DMPA former users surveyed had failed to conceive. In a smaller scale study by Fotherby et al, the conception rate among discontinuers of norethisterone enanthate did not differ significantly from that among nonusers of contraception or users of nonsteroidal methods once an 8-week period for the clearance of norethisterone from the body had elapsed. The mean time to ovulation is similar to the clearance for norethisterone; for DMPA, in contrast, the mean time to ovulation is considerably longer than that of the clearance. In discontinuers of DMPA, the mean time for the return of ovulation (210 days) is only slightly less than the mean time for the return of fertility (260 days). However, for norethisterone enanthate, the mean time to conception is about 170 days compared to just over 80 days for the return of ovulation.
PMID 12315276 12315276 DOI 10.3109/01443618609081724 10.3109/01443618609081724 Fotherby et al. 1986, Fotherby 1986
Cite this article
Fotherby, K., & Howard, G. (1986). Return of fertility in women discontinuing injectable contraceptives.. Journal of obstetrics and gynaecology, 6 Suppl 2, S110-5. https://doi.org/10.3109/01443618609081724
Fotherby K, Howard G. Return of fertility in women discontinuing injectable contraceptives.. Journal of obstetrics and gynaecology. 1986;6 Suppl 2:S110-5. doi:10.3109/01443618609081724
Carmina E et al., 2026·Journal of clinical medicine
Irregular menses and chronic anovulation are key components of Polyendocrine Metabolic Ovarian Syndrome (PMOS), but available treatments generally only mask the clinical problem, which presents itself again when the drugs are stopped. Because reduction of body weight in these patients is often associated with improvement of menstrual cycles, we evaluated the effects of treatment with semaglutide, a GLP-1 agonist that has emerged as an effective treatment for obesity. A total of 96 women with PMOS and body mass index (BMI) > 25 kg/m2 completed a six-month treatment protocol with semaglutide using an individualized dose-escalation regimen. Body weight, fasting glucose, insulin levels, insulin resistance (HOMA-IR), and ovulatory function were assessed before and after treatment. After six months of treatment, mean body weight decreased significantly (-11.3 ± 5%, p < 0.01). Before treatment, 83% of PMOS patients presented with oligomenorrhea and anovulatory cycles. Following treatment, ovulatory cycles were observed in 52.5% of previously anovulatory women. The results were particularly good in overweight patients, with almost 95% of these PMOS patients achieving menstrual cycle normalization and ovulation, but also in patients with mild obesity. Results were less favorable in PMOS patients with moderate or severe obesity, but 25% of these patients achieved menstrual ovulatory cycle normalization when treated with semaglutide. This study represents an important therapeutic advancement, suggesting that women with PMOS and excessive body weight should be considered for treatment with GLP-1 receptor agonists before proceeding to therapies specifically aimed at inducing normal cycles and ovulation.
Reimão Miller KA et al., 2026·Reproductive biomedicine online
This review explores whether the clomiphene citrate stair-step protocol (SSP) for ovulation induction in patients with polycystic ovary syndrome (PCOS) outperforms the traditional protocol. The following databases were searched: PubMed, Cochrane Library, ClinicalTrials.gov, EMBASE and Google Scholar from inception to 15 June 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and with PROSPERO registration (CRD420251050294). Of 847 screened records, five randomized controlled trials were included (n = 520: n = 255; traditional protocol: n = 265). Analyses were conducted in Review Manager 5.4 using random-effects models. Risk ratios, mean differences and 95% confidence intervals were calculated. Heterogeneity was assessed with I², risk of bias with RoB2, certainty with GRADE and robustness with leave-one-out sensitivity analysis. The SSP increased ovulation rates compared with the traditional protocol (RR 1.28, 95% CI 1.10 to 1.49; five randomized controlled trials [RCTs], n = 520, I² = 0%). Clinical pregnancy also favoured SSP (RR 1.46, 95% CI 1.04 to 2.05; four RCTs, n = 460; I² = 0%), although this result was largely driven by one study. The SSP shortened treatment duration (mean difference -32.59 days, 95% CI -38.66 to -26.52 days; three RCTs, n = 320, I² = 83%). Endometrial thickness was similar (mean difference 0.32 mm, 95% CI -0.95 to 1.59 mm; four RCTs, n = 460, I² = 91%). SSP improves ovulation rate and shortens treatment without affecting endometrial thickness and may increase clinical pregnancy rates.
Clomiphene citrate (CC) is the first-line medication for inducing ovulation in women with polycystic ovary syndrome (PCOS). However, approximately 20% of patients with PCOS are resistant to CC. This study aims to identify reliable baseline predictors of CC resistance in infertile women with PCOS. A post-hoc analysis of a large, multicenter randomized controlled trial (PCOSAct trial) conducted in China. The current analysis comprised the 471 participants who were randomized to the active CC arm and completed the requisite follow-up. To identify potential candidate variables, we employed multivariable logistic and LASSO regression analyses. Within the framework of a multivariable logistic regression model, we also estimated the independent associations between the identified candidate variables and resistance to CC. Additionally, we plotted the Receiver Operating Characteristic (ROC) curve and utilized the DeLong method to compare the statistical differences in the area under the curve (AUC). Finally, we constructed a restricted cubic spline (RCS) logistic regression model to illustrate the dose-response relationship between continuous predictor variables and CC resistance. CC resistance was identified in 32 (6.8%) participants. Body Mass Index (BMI), Total Testosterone (TT), and Anti-Müllerian Hormone (AMH) were useful predictors of ovarian response to CC. The "T+BMI" dual-factor model demonstrated high discriminative power (AUC = 0.801) and was statistically comparable to the three-factor model including AMH (AUC = 0.818; P = 0.347). TT was the strongest individual predictor (OR = 2.73 per 1-unit), while BMI was the most significant modifiable risk factor (OR = 2.49 per 1-SD). A simplified "T + BMI" assessment provides comparable prognostic utility without the need for AMH testing. For patients at high risk of CC resistance, we recommend upfront use of aromatase inhibitors or low-dose gonadotropins. This strategy avoids ineffective treatment cycles and enables personalized ovulation induction. The study was registered on ClinicalTrials.gov under the identification number NCT01573858 on July 6, 2012.
menstrual-cycle/cycle-disorders/dysmenorrheagynecology/pelvic-pain/chronic-pelvic-painreproductive-endocrinology/ovulation-physiology/anovulation
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