Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.
Eden, J. A., Place, J., Carter, G. D., Jones, J., Alaghband-Zadeh, J., & Pawson, M. E. (1989). The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Obstetrics and gynecology, 73(2), 187-190.
Eden JA, Place J, Carter GD, Jones J, Alaghband-Zadeh J, Pawson ME. The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Obstet Gynecol. 1989;73(2):187-190.
Eden, J. A., et al. "The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume." Obstetrics and gynecology, vol. 73, no. 2, 1989, pp. 187-190.
To identify a distinctive constellation of persistent visual abnormalities secondary to treatment with clomiphene citrate. Description of the clinical findings in three patients with visual disturbance secondary to clomiphene treatment. A neuro-ophthalmology referral center. Three women aged 32 to 36 years treated for infertility with clomiphene for 4 to 15 months. All three patients experienced prolonged afterimages (palinopsia), shimmering of the peripheral field, and photophobia while undergoing treatment with clomiphene. The results of the neuro-ophthalmologic examination and electrophysiologic studies were normal in all three patients. Unlike previously reported cases, visual symptoms did not resolve on cessation of treatment. Patients remain symptomatic from 2 to 7 years after discontinuing treatment with the medication. Treatment with clomiphene can cause prolonged visual disturbance. Patients who develop such symptoms should be advised that continued administration may cause irreversible changes. Women with characteristic visual symptoms should be questioned about past use of clomiphene.
InfertilityClomiphene Citrate Side EffectsClomiphene EffectsDrug-Induced Changes
To analyze the effects of clomiphene citrate (CC) on cervical mucus (CM) and endometrial morphology independently of hormonal changes encountered when CC is administered for ovulation induction. Volunteers whose ovarian functions were temporarily suppressed (n = 18) by a long-acting GnRH agonist and 6 women of similar age suffering from premature ovarian failure (POF) received E2 and P. Half of the women also received CC (50 mg/d, days 2 to 6). Tertiary University Institution, Hôpital A. Béclère. PATIENTS, Eighteen volunteers suffering from infertility not related to a uterine cause and 6 women of similar age suffering from POF. Plasma gonadotropins, E2, and P were measured at baseline to confirm that the ovaries were inactive and twice weekly during physiological E2 and P replacement. Cervical mucus was analyzed on day 14 and scored from 0 to 15. Endometrial biopsies were obtained on replacement days 20 and 24 for conventional histology and immunocytochemistry analysis of estrogen receptors and progesterone receptors (PR). Premature ovarian failure women whose results have been previously published served as controls for day 20 biopsies. Cervical mucus scored lower in women who received CC (5.5 +/- 3.2) than in controls (13.6 +/- 4.7, mean +/- SEM). On day 20, endometrial findings were similar in women treated with CC and in controls. On day 24, specimens showed a significant delay in endometrial maturation in women treated with CC. On day 24, only staining for PR selectively persisted in endometrial stroma, and no difference was observed between women who received CC and controls. Our results indicate that CC significantly alters CM quality and late luteal phase endometrial morphology despite physiological levels of plasma E2 and P. Hence, clinicians should monitor E2 levels when using CC, and caution should be exerted when supraphysiological levels of E2 are not present to counterbalance the effects of CC on the CM and the endometrium.
InfertilityClomiphene Citrate Side EffectsHormonal InfluencesAnti-Estrogenic Effects
The antiestrogenic effect of clomiphene citrate (CC) on cervical mucus was evaluated in women receiving 150 mg CC daily for 5 days. Daily cervical mucus scores and serum estradiol (E2) concentrations were determined in control (n = 25) and CC (n = 24) cycles. E2 concentrations were significantly higher in the CC-treated women (mean +/- standard error of the mean, 1254 +/- 102 pg/ml versus 337 +/- 18 pg/ml, P less than 0.0001). Despite supraphysiologic E2 concentrations, however, cervical mucus scores were significantly reduced in the CC-treated group (P less than 0.01). These data indicate that CC exerts a direct suppressive effect on cervical mucus despite markedly increased E2 concentrations.
EndometriosisFertility OutcomesEndometriosis Surgery ClaimsReproductive Treatment Access
For many patients with endometriosis, laparoscopic surgery is the most effective treatment to alleviate severe chronic pelvic pain and improve quality of life. Because endometriosis is common among individuals with infertility, surgery is often considered alongside fertility evaluation and treatment to manage symptoms, identify disease pathology, and restore pelvic anatomy. In patients who desire pregnancy, the decision of whether and when to pursue surgery should be guided by clear medical indications and shared decision making between the patient and their obstetrician-gynecologist. In recent months, however, religious and political groups have sought to reframe this medical decision as an ideologic and moral one, advocating for endometriosis surgery in nearly all patients with infertility and claiming that this can eliminate the need for assisted reproductive technologies. This framework, known as restorative reproductive medicine (RRM), aligns with efforts to promote the "personhood" of fertilized eggs, restrict access to in in vitro fertilization (IVF), and advance endometriosis surgery and lifestyle modifications as "root-cause treatment leading to natural fertility." Recent editorials and issue briefs in the obstetrics and gynecology literature have discussed the serious ethical, medical, and policy implications of RRM, yet there remains an urgent need to address specifically the unfounded claims about endometriosis surgery and its purported advantages over assisted reproductive technology. This article examines the social context of this controversy and reviews the current evidence regarding the indications, benefits, and limitations of endometriosis surgery in the management of infertility. In contrast to RRM's assertions, no evidence supports the adoption of endometriosis surgery as a replacement for IVF or as a primary treatment for infertility. Rather, the role of surgery in fertility care is highly nuanced and depends on each patient's clinical presentation, reproductive goals, and personal priorities.