Antiestrogenic Effect Of Clomiphene Citrate Research Articles

Effects of clomiphene citrate plus estradiol or progesterone on endometrial ultrastructure: An RCT.

BackgroundPinopods concentrations in endometrial surface is a marker of implantation. Estradiol valerate (EV) was used to change the adverse effects of Clomiphene Citrate (CC) on the endometrium.Objective The goal was to assess whether there is a significant difference in the endometrial pinopods concentrations and other parameters after adding EV and progesterone to higher doses of CC.Materials and MethodsIn this prospective randomized clinical trial, a total of 30 women who did not respond to 100 mg of CC from February 2016 to June 2016 were evaluated. They were divided into three groups: group I) received 150 mg of CC alone, group II) CC with EV, and group III) CC plus progesterone. On day 21 of the menstrual cycle, endometrial biopsy, a blood sampling, and a scanning by electron microscopy were performed.ResultsOn day 21 of the menstrual cycle, there was no significant difference in the pinopods concentrations (p = 0.641) and serum estrogen levels (p = 0.276) between groups. However, the Serum progesterone levels in group I was higher than the other two groups (p = 0.007) in the same day.Conclusion Since the addition of EV and progesterone to higher dosages of CC did not change the pinopods concentration and serum estrogen levels on day 21 of the menstrual cycle, and the serum progesterone levels was higher in CC alone group (i.e. group I) compared to other groups, it can be concluded that the anti-estrogenic effects of CC just appear on the endometrium and not on the plasma levels.

Use of phytoestrogen with clomiphene citrate for ovulation induction in polycystic ovary syndrome

The goal of this study is to assess the effectiveness of phytoestrogen with clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome to overcome the antiestrogenic effect of clomiphene citrate on endometrium, were randomly grouped into two groups, 50 in each group. Group 1: receiving CC 100 mg twice daily from third day of cycle for five days and group 2: receiving CC from 3rd of cycle for 5 days plus phytoestrogen (Klimadynon(®), Bionorica, Neumarkt i.d.OBf., Germany) (20mg of cimifuga racemosa from day 1to12). Women receiving CC plus phytoestrogen have an increase number of dominant follicles, endometrial thickness with an improvement of both ovulation rate and pregnancy rate.

Abstracts of the 23rd Annual Congress of the SBRA, Curitiba/PR, 2019

Obejective:Despite recent advances in assisted reproduction techniques, implantation and birth rates remain low. Although embryo quality is considered the main determinant of implantation success, maturity and endometrial receptivity are also important factors to consider. However, what precisely constitutes a receptive endometrium remains uncertain. The objective of this study is to investigate if clomiphene citrate alters the endometrial maturation in infertile patients.Methods: In a prospective self-matched cohort study, the ovulation of women was evaluated in spontaneous and stimulated cycles (with clomiphene citrate). Subjects were submitted to transvaginal ultrasounds to follow the cycle and to determine the day of ovulation. In both cycles, four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) were taken to determine the serum concentrations of FSH, LH, estradiol and progesterone. An endometrial biopsy was performed five days after ovulation in both cycles and sent to Hospital de Clínicas de Porto Alegre pathology lab for analysis and classification according to Noyes criteria.Results:Twenty-two participants completed the study protocol. There were significant differences in FSH BS3 (p = 0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p = 0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day.Discussion: This study indicates that the ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process. The antiestrogenic effects of clomiphene citrate in the endometrium may be responsible for this difference and, to avoid this effect, it is suggested to consider the freeze-all strategy when using clomiphene citrate for controlled ovarian stimulation, in order to minimize the endometrial asynchrony.

Effects of letrozole and clomiphene citrate on Wnt signaling pathway in endometrium of polycystic ovarian syndrome and healthy women†.

Polycystic ovary syndrome (PCOS) is an endocrine disorder in women of reproductive age. In addition to anovulation, endometrial dysfunction can reduce fertility in PCOS. The cyclical changes of endometrium are controlled by estrogen and progesterone via modulating the Wnt/B-catenin pathway. Clomiphene citrate (CC) and letrozole are used to induce ovulation; unlike letrozole, there is a discrepancy between ovulation and pregnancy rates in CC-treated cycles. Because of the anti-estrogenic effects of CC on endometrium, we compared the expression of the key molecules of the Wnt/B-catenin pathway in the endometrium of women taking CC and letrozole. This study included PCOS and healthy women divided into the groups stimulated with letrozole (5 mg) or CC (100 mg) as well as NO-treatment groups. The endometrial thickness and hormonal profile were measured on day 12 of the menses. Using real-time polymerase chain reaction and western blot, we evaluated mRNA and protein expression of B-catenin, glycogen synthase kinase 3 beta (GSK3B), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), and estrogen receptor 1 (ESR1) in the endometrial samples. Significantly, the mean serum estrogen and progesterone were lower and higher, respectively, in letrozole than CC groups. The endometrial thickness was significantly reduced in CC. The proteins expression of active B-catenin, inactive GSK3B, and ESR1 were significantly decreased in CC-treated groups. The mRNA and protein assessment of DKK1 showed significantly higher expression in CC. Our results indicate that letrozole can provide an acceptable activation of the Wnt/B-catenin pathway, resulting in adequate proliferation of endometrium in the women receiving letrozole compared to CC.

Clomiphene Citrate and Oocyte Quality

The clomiphene citrate (CC) is a first line of medicine used for ovulation induction in women worldwide. CC has good ovulation induction ability in anovulatory women but the pregnancy rate is very poor. This discrepancy might be due to the anti-estrogenic effect of CC at various level including ovary and oocytes. The hypoestrogenic conditions due to CC treatment inhibit follicular growth and development, induce susceptibility of oocytes towards apoptosis and deteriorate oocyte quality after ovulation. CC induces reactive oxygen species (ROS) mediated granulosa cells as well as oocyte apoptosis within the follicle of the ovary. Apoptosis deteriorates oocyte quality and thereby reproductive outcome. Supplementation of estradiol 17I² or natural antioxidant such as melatonin prevents anti-estrogenic effects of CC and improves oocyte quality by scavenging CC induced generation of ROS. Thus, we propose that the supplementation of estradiol 17I² and/or melatonin along with CC may be beneficial to overcome the anti-estrogenic effect of CC during infertility management in human.

Peri-ovulatory Phytoestrogen Improves Pregnancy Rate in Women with Polycystic OvarianSyndrome Receiving Ovulation Induction with Clomiphene Citrate

Background: PCOS is the most common ovarian factor of female infertility, in low resource countries clomiphene citrate is the most popular drug used for induction of ovulation as its price is affordable for most of patients with least side effects. Objective: Evaluate the effect of phytoestrogen in women receiving induction with clomiphene citrate when given peri ovulatory to oppose antiestrogenic effect of clomiphene citrate. Methodology: Prospective study conducted on 500 patients with PCOD who attended infertility clinic, patients were randomized into 2 groups both groups received traditional CC induction , group (1) 225 patients received phyto-estrogen, starting in the 7th day of the cycle till the day of HCG injection ,group(2) 225 patients received clomiphene citrate only. Endometrial thickness and follicular growth were assessed by transvaginal US. When follicles reached 18 mm, 10,000 IU HCG was administered together with timed intercourse. Both groups were compared as regard cumulative pregnancy rate, ovulation, endometrial thickness and change in hormonal milieu. Results: Midluteal serum progesterone was significantly higher in the study group as compared with the control group (15.93 ±1.8 versus 12.93 ± 1.8); endometrial thickness was also greater in the study group as compared with the control group, (10.3 ± 1.1 versus 8.2 ± 0.9). Ovulation in the three cycles was in favor of study group 82.5% versus 80.4% but not statistically significant. The CPR was significantly higher in the study group than in the control group (34.2% vs. 20.8%. P = 0.1). There were 6 cases of multiple pregnancy in the study group and 4 cases in the control group. Conclusion: Adding phytoestrogen to CC induction improve ovulation and pregnancy rate, it is a good option for patients with PCOS seeking for pregnancy treatment with affordable price and minimal side effects

Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes

The clomiphene citrate (CC), a nonsteroidal triphenylethylene compound, is a first line of medicine used for the induction of ovulation in anovulatory women worldwide. In spite of high ovulation induction with the use of CC, the pregnancy rate is much lower. Such a discrepancy could be due to the peripheral anti-estrogenic effect of CC, particularly at the level of ovary, endometrium and cervical mucus. CC induces ovulation by binding to the estrogen receptors and generates hypoestrogrnic state in hypothalamus leading to release of pituitary gonadotropins. CC may have a direct effect at the level of ovary but the molecular mechanism remains unclear. Animal studies suggest that the CC induces apoptosis in granulosa cells and results hypoestrogenic state in the ovary. Reduced estradiol 17β level in the ovary affects development and maturation of oocyte leading to oocyte apoptosis. Further, CC increases hydrogen peroxide (H2O2) level and thereby bax protein expression and DNA fragmentation in cumulus-granulosa cells as well as in oocytes. The exogenous supplementation of either estradiol 17β or melatonin reduces H2O2 level in ovary, delays meiotic cell cycle progression in oocyte and protects oocyte apoptosis. Hence, supplementation of estradiol 17β or melatonin along with CC could be beneficial to protect granulosa cell as well as oocyte apoptosis and inhibit deterioration of oocyte quality. Thus, maintenance of oocyte quality may overcome the adverse effect caused due to CC treatment during infertility management.

Clomiphene citrate potentiates the adverse effects of estrogen on rat testis and down-regulates the expression of steroidogenic enzyme genes

To investigate the antiestrogenic effect of clomiphene citrate (CC) in male rats estrogenized with estradiol-3-benzoate (EB). Prospective experimental study. Laboratory. Adult male albino rats (Holtzman strain). CC was given alone or in combination with EB. Testicular function and steroidogenic enzyme gene expression were evaluated in control versus treated groups. EB after 30 days of treatment induced a rise in TUNEL-positive germ cells adversely affecting spermatogenesis with complete absence of elongated spermatids or sperms. CC alone had only a moderate effect. In contrast, CC+EB synergistically inflicted more adverse effects as apoptotic germ cells per tubule rose further. Significant down-regulation in expression of testicular steroidogenic enzyme genes StAR, p450scc, 3β-HSD, and p450c17 was observed. In the EB-alone group, aromatase gene expression in the testis was up-regulated but reversed in brain and liver tissues. CC alone had little modulatory effect on aromatase expression. On the other hand, CC+EB countered the EB-induced rise of aromatase expression in the testis. The above findings indicate that CC in the presence of estrogen synergistically potentiates more adverse effects in testis, inhibiting expression of upstream steroidogenic enzyme genes and leading to disruption of steroidogenesis.

Vitamin E effect on controlled ovarian stimulation of unexplained infertile women

To determine Vit E effect on the treatment outcomes of women with unexplained infertility undergoing controlled ovarian stimulation and intrauterine insemination (IUI). The study group (Group A, n053) underwent controlled ovarian stimulation with clomiphene citrate with Vit E administration, 400 IU/day p.o. while the control group(Group B, n050) underwent ovulation induction without VitE. Treatment outcomes were compared between the groups. There were no significant differences between the two groups with respect to the demographic outcomes. The difference in endometrial thickness on the day of hCG administration was significant between the two groups (p00.001).The effect of receiving Vit E on the implantation and the on going pregnancy rates were assesed Odds Ratio (OR) and corresponding 95% Confidence Intervals (CI). Receiving Vit E was not significantly associated with the implantation and the ongoing pregnancy rates; OR 0 1.22, 95% CI (0.44–3.4)and OR 0 1.43, 95% CI (0.49–4.1), respectively. Vit E administration may improve the endometrial response in unexplained infertile women via the likely antioxidant and the anticoagulant effects. It may also modulate the antiestrogenic effect of clomiphene citrate and the problem of a thin endometrium in these cycles may beadjusted

Molecular Mechanism of the Inhibition of Estradiol-Induced Endometrial Epithelial Cell Proliferation by Clomiphene Citrate

We examined the molecular mechanisms of the antiestrogenic effects of clomiphene citrate (CC) in the endometrium using two types of cell lines, Ishikawa and EM-E6/E7/hTERT cells. CC or ICI182780 inhibited 17beta-estradiol (E2)-induced endometrial cell proliferation and transcriptional activation of the estrogen response element (ERE) gene. We directly visualized the ligand-estrogen receptor (ER)alpha interaction using green fluorescent protein (GFP)-tagged ER alpha in a single living cell. Whereas E2 changed the nuclear localization of GFP-ER alpha to a punctate distribution within 5 min, CC or ICI182780 changed the slower and less mobilization of GFP-ER alpha compared with E2. Pretreatment with CC or ICI182780 partly prevented the E2-induced nuclear redistribution of GFP-ER alpha. Fluorescence recovery after photobleaching revealed that GFP-ER alpha mobility treated with E2 was more rapid than that treated by CC or ICI182780. As coactivator recruitment to the ER is essential for ER-dependent transcription, we examined the interaction between ER alpha and steroid receptor coactivator-1 (SRC-1). The complex formation between ER alpha and SRC-1 was significantly increased by E2 but was prevented in the presence of CC or ICI182780 by coimmunoprecipitation. Moreover, the E2-induced colocalization of GFP-ER alpha and SRC-1 was prevented in the presence of CC or ICI182780 according to an immunofluorescence assay. We also observed that the reduction of SRC-1 using small interfering RNA for SRC-1 resulted in the inhibition of E2-induced cell proliferation and transcriptional activation of the ERE gene. Collectively, these results suggest that CC may inhibit E2-induced endometrial epithelial cell proliferation and ERE transactivation by inhibiting the recruitment of SRC-1 to ER alpha.

Aromatase Inhibitors in Infertility Treatment: Risks and Benefits

Ovulatory disorders (such as polycystic ovary syndrome [PCOS]) are commonly treated with clomiphene citrate (CC), with rates of ovulation ranging between 50 and 90%. However, even though the majority of pregnancies occur within the first three cycles of treatment [1], the overall pregnancy rates are disappointingly low, ranging from 20–40% [2–4], and the likelihood of miscarriage is relatively high [5]. This discrepancy between high rates of ovulation and low rates of pregnancy is believed to be a consequence of the antiestrogenic effect of CC on peripheral targets, such as the endometrium (affecting its thickness and maturation) and the endocervix (affecting the production and quality of cervical mucus). The problem is compounded by the long half-life of CC and the persistence of an isomer, zuclomiphene, both of which lead to an accumulating antiestrogenic effect with consecutive cycles of treatment [6]. In addition, due to the prolonged occupation of estrogen receptors by CC in the hypothalamus, the circulating amount of estrogen may rise to high levels from ongoing stimulation of the follicles by endogenous follicle-stimulating hormone (FSH) production. Such supraphysiological levels of estrogen may be deleterious to the developing oocyte, sperm and embryo [7]. Consequently, better methods for inducing ovulation are desirable. Studies in animals suggest that aromatase, an enzyme necessary to convert androgens to estrogen, could be a potential target for the inhibition of estrogen production. Aromatase inhibitors (AIs) increased gonadotropin levels and ovarian weight in female rats [8], and have been found to produce multiple ovarian follicles in female primates [9]. The new generation of AIs (anastrozole, letrozole and vorozole) have more specific action, fewer side effects and lower

Study of the Effect of Clomiphene Citrate on Oocyte and Embryo Quality Using the Oocyte Donation Model

Despite high ovulation rates in anovulatory women treated with clomiphene citrate (CC), pregnancy rates remain disappointingly low probably due to the anti estrogenic effects of CC on the uterus. Also, several studies suggest CC might have a deleterious effect on the oocytes of treated rats. Ovarian hyperstimulation with CC and gonadotropins using the oocyte donation model allows differentiation of the effect of CC on pregnancy rates due to its effect on the donor’s oocytes from its anti estrogenic effect on the endometrium since recipient women are not exposed to CC.

Effect of repeated administration of clomiphene citrate at two different times on the endometrium in patients undergoing intrauterine insemination.

Background, Aims and Methods: Clomiphene citrate (CC) has been widely used for induction of ovulation; however, despite the high rate of ovulation, the pregnancy rate is only 30%. The anti-estrogenic effect of CC on the endometrium is one explanation for this finding. It is well known that repeated administration of CC enhances its anti-estrogenic effect. To overcome this adverse affect, a number of techniques have been used. One technique is the early administration of CC, in an attempt to decrease the anti-estrogenic effects of CC on the endometrium. The aim of the present study was to retrospectively evaluate if repeated administration of CC at varying times may affect the endometrium during preovulatory period; pregnancy rates were compiled for patients with unexplained infertility undergoing intrauterine insemination (IUI). The patients were divided into four groups based on the number of repeat administrations and the time of CC administration. Results: The endometrial thickness at the day of human chorionic gonadotropin administration was greater in early administration within three consecutive CC cycles than the others. Conclusion: When the endometrium is thin during classical administration of CC, it is worth attempting the early administration of CC in the CC/IUI treatment for patients with unexplained infertility. However, this effect disappeared over the duration of the three consecutive CC cycles. (Reprod Med Biol 2004; 3: 153-157).

High Dose of Phytoestrogens Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on the Endometrium in Patients Undergoing Intrauterine Insemination: A Randomized Trial

To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study. A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted. A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.

Effects of Tamoxifen (Tx) on Endometrial Thickness and Pregnancy Rates in Women Undergoing Superovulation with Clomiphene Citrate (CC) and Intrauterine Insemination (IUI)

Objective: CC is commonly used to either provoke ovulation in anovulatory patients, or to increase the number of pre-ovulatory follicles in ovulatory patients prior to IUI. However, pregnancy rates following induction with CC and IUI are lower than expected for the number of follicles produced. This may be a result of the anti-estrogenic effect of CC on the endometrium. Tx has been previously been shown to act as an estrogen agonist on endometrial cells causing, after prolonged use, endometrial hyperplasia. In this study we investigated the potential positive effect of Tx on the endometrium, and pregnancy rates in patients treated with CC prior to IUI.

Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study

Objective: To compare the effectiveness of clomiphene citrate used alone and in combination with ethinyl E 2 for the induction of ovulation in patients undergoing IUI. Design: Randomized, double-blind study. Setting: Four infertility treatment centers. Patient(s): Women aged 25–35 years with infertility of at least 2 years’ duration and oligomenorrhea or amenorrhea associated with a positive menstrual response to an IM progesterone challenge. Intervention(s): A total of 64 patients were randomized to treatment with CC (100 mg daily for 5 days) or CC (100 mg daily for 5 days) plus ethinyl E 2 (0.05 mg daily for 5 days). Main Outcome Measure(s): The uterine artery pulsatility index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. Result(s): Both treatment regimens increased FSH, LH, and 17β-E 2 levels, with no statistically significant differences. There was a statistically significant difference in endometrial thickness between the two treatment groups. No statistically significant differences were noted in pulsatility index values or in the number of preovulatory follicles. Conclusion(s): Ethinyl E 2 can reverse the deleterious effects of CC on endometrial thickness, which may contribute to higher pregnancy rates.

Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs

Objective: To investigate whether the timing of administration of clomiphene citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates. Design: Prospective, randomized, double-blind trial. Setting: Academic center. Patient(s): Twenty-three patients with unexplained infertility. Intervention(s): Twenty-three patients with unexplained infertility underwent 45 cycles of CC and IUI. For each cycle, patients were randomized either to receive 100 mg of CC on days 1–5 and placebo on days 5–9 (study group), or placebo on days 1–5 and CC on days 5–9 (control group). Main Outcome Measure(s): The difference in uterine artery PI, number of follicles, endometrial thickness, and pregnancy rates. Result(s): Gonadotropins and E 2 levels, as well as uterine artery pulsatility index, were significantly higher in the study group on day 5. In addition, in the study group, a longer time interval existed between finishing CC and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1–3) and the pregnancy rate was higher than in the control group (6 versus 0; OR = 15.1; 95% CI = 1.1–72.4). Conclusion(s): Clomiphene citrate commenced on day 1 of the menstrual cycle, rather than day 5, results in more rapid follicular growth, a longer CC-free period before IUI, and higher pregnancy rates. Although methodologically sound, our results should be taken with some degree of caution because they are based on a relatively small number of patients.

Transabdominal ultrasonographic evaluation of endometrial thickness in clomiphene citrate-stimulated cycles in relation to conception.

The possible antiestrogenic effect of clomiphene citrate on endometrial growth was assessed by serial transabdominal ultrasonographic measurements in 46 women with unexplained infertility. A significantly higher (p < 0.05) rate of endometrial growth was observed in the 8 women who conceived compared with the 38 women who failed to conceive. A thicker endometrium (4.6 +/- 0.3 mm) was observed from the third day before ovulation as well as a higher average growth rate in the three days prior to ovulation (0.7 +/- 0.1 mm/day) in the group that achieved pregnancy compared to a lower endometrium (2.1 +/- 0.2 mm) from the third day before ovulation and a slower growth rate in the three days prior to ovulation (0.2 +/- 0.0 mm/day) in the group that did not achieve pregnancy (p < 0.05). These data suggest that clomiphene citrate may exert an antiestrogenic effect on the endometrium, and thus interfere with implantation.

The effect of clomiphene citrate and menopausal gonadotropins on cervical mucus in ovulatory cycles

To determine the effect of clomiphene citrate (CC) and hMG on cervical mucus (CM), optimally sampled in the periovulatory period from confirmed ovulatory cycles, in the dosage range commonly employed for ovulation induction. Controlled, observational. Infertility treatment center at a university medical center. One hundred fifty-four infertile patients undergoing 161 treatment cycles in which postcoital test was performed in a documented ovulatory cycle. One hundred six patients received CC at dosages of 50 to 200 mg. Twenty patients received hMG at dosages of 75 to 225 IU. Thirty-seven patients sampled during spontaneous ovulatory cycles served as controls. Cervical mucus score using standardized scoring criteria. Subjects receiving CC at all dosages had significantly lower CM scores 8.6 +/- 0.5, compared with patients receiving hMG 11.0 +/- 0.6 or spontaneous cycles 12.1 +/- 0.5. The incidence of unfavorable CM (score < 10/15) was similar in patients receiving CC at dosages of 50 mg (48.1%), 100 mg (48.6%), and 150 to 200 mg (60%). Cervical mucus scores are reduced in ovulatory cycles after CC administration compared with both spontaneous ovulatory cycles and in patients undergoing superovulation with hMG. The reduction in CM scores was similar at all dosages of CC studied. The lack of adverse effects on CM during hMG therapy supports a local antiestrogenic effect of CC at the level of the cervix.

Detection of premature luteinization with serum progesterone levels at the time of the postcoital test

Poor cervical mucus (CM) may be caused by a number of factors, including premature luteinization, local cervical effects, and inadequate folliculogenesis. In an attempt to distinguish between these causes of poor CM, we obtained progesterone (P) levels at the time of postcoital tests (PCTs) in infertile women during spontaneous or clomiphene citrate (CC)-stimulated cycles. The amount of CM, viscosity, ferning, spinnbarkeit, and cellularity were each scored from 0 to 3 points on the day after detection of the urinary luteinizing hormone surge (luteal day 1). The charts of 46 such patients were retrospectively reviewed. Eleven control patients with good CM scores (greater than 10) had low P levels (less than 2.5 ng/mL). Of the remaining 35 cycles, 19 were marked by low P levels, and 16 were accompanied by P levels of greater than 2.5 ng/mL. Overall, 94.4% of CC-stimulated cycles versus 64.3% of spontaneous cycles had abnormal CM scores (less than 9). On the basis of these inappropriately elevated P levels, premature luteinization can be cited as the cause of poor mucus quality. In fact, premature luteinization may be responsible for some of the purported antiestrogenic effects of CC. Therefore, it is appropriate to draw a P level at the time of a poor PCT, particularly in cycles stimulated by CC.