Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome.

BACKGROUND: The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity. METHODS: Retrospective case-control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase. RESULTS: Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%). CONCLUSIONS: CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome

Background.?The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity.

Methods.?Retrospective case–control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase.

Results.?Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%).

Conclusions.?CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

促排卵周期PCOS妇女子宫内膜纤维粘连蛋白及层粘连蛋白的表达

目的:了解促排卵药物氯米酚(CC)、hMG及GnRH-a对黄体中期子宫内膜内膜纤维粘连 蛋白(FN)及层粘连蛋白(LN)表达的影响。方法:应用单克隆抗体,采用免疫组织化学技术检测50 例正常妇女自然周期以及50例正常妇女,45例多囊卵巢综合征妇女应用CC／hCG,CC／hMG／hCG 及GnRH-a／hMG／hCG方案促排卵治疗后黄体中期子宫内膜FN和LN的表达。结果:子宫内膜FN 和LN表达在正常妇女自然周期着床窗口时呈现强阳性;而CC、hMG抑制FN和LN的表达,使 其阳性强度减弱,有显著性统计学差异P<0．01;GnRH-a对FN和LN抑制不明显。同时妊娠者较 未妊娠者FN和LN表达强度高。结论:CC／hCG及CC／hMG／hCG方案促排卵后黄体中期子宫内膜 中FN和LN表达下降或缺失,内膜容受性下降,妊娠率降低。     

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate

OBJECTIVE: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. DESIGN: Prospective trial in infertility patients treated with CC. SETTING: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.     

Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction

Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.     

"Ovulation during lactation" as determined by endometrial biopsy

A study was conducted at the Lady Hardinge Medical College and Hospital in New Delhi, India with the objective of determining the frequency of ovulation during lactation. It is now accepted that the most satisfactory proof of ovulation is the presence of a secretory endometrium late in the menstrual cycle. The histology of endometrium was the only method of study for the presumptive evidence of ovulation employed in this investigation. Out of a total of 197 endometrial biopsies, 77 were obtained from menstruating women, and 120 were obtained from women who had amenorrhea. Of these 98 were taken during lactational amenorrhea in 89 cases. Out of 77 biopsies from the menstruating group, 30 were obtained from 26 lactating mothers. The biopsies during amenorrhea of lactation showed that the proportion of biopsies revealing inactive endometrium increases with the duration of amenorrhea. It was also observed that it is often impossible to obtain any endometrial tissue if the period of amenorrhea has been prolonged. In 31.6% of the specimens there was no sign of growth or activity of the endometrium. The endometrium corresponding to late and midproliferative phase was found only if the biopsy was taken within 3 months after delivery. 16% of the 1st cycles in lactating mothers were ovular (total 12 biopsies) and 57% of 1st cycles in nonlactating women were ovular. The finding suggests that lactation does inhibit ovulation in addition to postponement of menstruation. Few biopsies were available for the subsequent cycles. In lactating women, 50% of the 2nd cycles and 83% of the 3rd cycles were ovular. In a fully lactating mother the earliest ovular biopsy was detected at 9 weeks postpartum. In 1 partially lactating and 3 nonlactating cases, ovular biopsies were obtained at 41 days postpartum. The endometrium tends to be atrophic as amenorrhea is prolonged, but this atrophy is reversible.     

Histological dating of timed endometrial biopsy tissue is not related to fertility status

OBJECTIVE: To assess the ability of histological dating to discriminate between women of fertile and infertile couples. The utility of histological dating of endometrium in the evaluation of infertile couples is uncertain. DESIGN: Prospective multicenter study, with subjects randomly assigned to biopsy timing. Criterion standard for infertility was 12 months of unprotected, regular intercourse without conception and for fertility at least one live birth within 2 years. SETTING: University-based infertility practices. PATIENT(S): Volunteer subjects (847) recruited at 12 clinical sites participating in the National Institutes of Health-funded Reproductive Medicine Network. Inclusion criteria included ages 20-39 years, regular menstrual cycles, and no hormonal treatment or contraceptive use for 1 month before the study. Fertile controls were excluded if they had a history of infertility, recurrent pregnancy loss, or recent breastfeeding. INTERVENTION(S): Subjects underwent daily urinary LH testing. After detection of the LH surge, subjects were randomized to biopsy in the mid (days 21-22) or the late (days 26-27) luteal phase. Pathologists at each site estimated the cycle day based on standard criteria. For the primary analysis, an out-of-phase biopsy was defined as a greater than 2-day delay in the histological maturation of the endometrium. MAIN OUTCOME MEASURE(S): The proportion of out-of-phase biopsies in fertile and infertile women was compared using logistic regression models with age at randomization as a covariate. Comparisons were also made between fertile vs. infertile at the midluteal or late luteal phase time points. RESULT(S): Biopsies were evaluated (301 mid and 318 late; N = 619). Out-of-phase biopsy results poorly discriminated between women from fertile and infertile couples in either the midluteal (fertile: 49.4%, infertile: 43.2%) or late luteal phase (fertile: 35.3%, infertile 23.0%). Results did not substantially differ using alternative definitions of "out-of-phase" or standardized cycle day. CONCLUSION(S): Histological dating of the endometrium does not discriminate between women of fertile and infertile couples and should not be used in the routine evaluation of infertility.     

自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

Effects of initiation day of clomiphene citrate on the endometrium of women with regular menstrual cycles

OBJECTIVE: To investigate the effects of initiation time of clomiphene citrate (CC) on the endometrium of women with regular menstrual cycles. DESIGN: Randomized, double-blind, cross-over study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. PATIENT(S): Thirty-three healthy female volunteers with regular menstrual cycles. INTERVENTION(S): The volunteers were randomized to receive either 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). After a wash-out period of 1 month of CC treatment, the medication was switched in each group. Ultrasonography was performed daily after day 10 of the cycle to detect ovulation. Ultrasonography for endometrial appearance and thickness, endometrial sampling, and blood samples obtained for determination of E(2) and P levels were performed 7 days after ovulation in both groups. MAIN OUTCOME MEASURE(S): Morphometric analysis, histologic dating, and ultrasonographic appearance and thickness of the endometrium. RESULT(S): Morphometric parameters, histologic dating, and ultrasonographic appearance and thickness of the endometrium were similar in both groups. CONCLUSION(S): Starting CC on either day 1 or day 5 of the menstrual cycle did not have any differential effects on the endometrium of women with regular menstrual cycles, particularly regarding the morphometric analysis, histologic dating, or ultrasonographic appearance.     

Midluteal endometrial biopsy and alphavbeta3 integrin expression in the evaluation of the endometrium in infertility: implications for fecundity.

It has been recently proposed that the immunohistochemical evaluation of alphavbeta3 integrin in combination with histologic dating in midluteal endometrial biopsy specimens should be performed to evaluate the endometrial receptivity in the infertile patient. However, no studies have attempted to correlate these findings with subsequent fecundity. In 100 consecutive infertile patients (mean age 31.9+/-3.4 years) undergoing a routine work-up, two endometrial biopsies were performed during a single menstrual cycle: a midluteal biopsy on postovulatory days 6 to 8 and another biopsy 4 days later. Histological dating and immunohistochemical evaluation of alphavbeta3 integrin expression were done in all endometrial biopsy specimens. All patients were followed without treatment during 18 to 24 months (mean 23.5+/-1.4, range 18 to 24). Twenty-five midluteal biopsies showed out-of-phase endometria, whereas all but one late-luteal biopsy specimens were in-phase. Glandular alphavbeta3 integrin expression was observed in 50% of midluteal specimens with this expression being significantly more frequent among in-phase (63%) than among out-of-phase (12%) specimens (p<0.001). However, all late-luteal specimens strongly expressed this integrin. Thirty-eight women became spontaneously pregnant during the follow-up period, 32 ended in a live birth and 6 in first trimester spontaneous abortion. The Cox regression method showed no differences between the hazard of pregnancy when the alphavbeta3 integrin-positive and -negative groups were compared (odds ratio 1.25; 95% confidence interval [CI] 0.66-2.36; p=0.49) or when patients with in-phase endometria were compared with those with delayed endometrial maturation (odds ratio 1.12; 95% CI 0.53-2.37; p=0.76). In conclusion, neither midluteal histological evaluation nor alphavbeta3 integrin expression in mid- or late-luteal endometrial biopsy specimens correlated with outcome for subsequently untreated infertile women.     

Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clomiphene citrate

OBJECTIVE: To assess the effect of clomiphene citrate (CC) on endometrial epithelial integrins and P receptors (PR) during the window of implantation. DESIGN: Controlled, prospective, clinical study. SETTING: Teaching hospital and university research laboratory. PATIENT(S): Thirty-one fertile, normo-ovulatory women participated in this trial. Thirteen women exhibited a CC-stimulated cycle with 50 mg on days 5-9, and 18 women with spontaneous menstrual cycles served as controls. INTERVENTION(S): Endometrial biopsies in the midluteal phase. MAIN OUTCOME MEASURE(S): Immunohistochemical determination and endometrial cellular localization of alpha1, alpha v, beta3, and alpha4 epithelial integrins and PR during the window of implantation. The staining intensity was assessed by a semiquantitative index (HSCORE) and compared by nonparametric Mann-Whitney test. RESULT(S): Higher plasma levels of P and E2 and delayed histologic dating of the endometrium (38%) were features of CC-treated women. In addition, a low epithelial beta3 integrin expression and persistent PR were observed in glandular epithelial cells of "out-of-phase" endometrial biopsies from CC-treated women. In contrast, in "in-phase" biopsies, neither epithelial PR nor beta3 integrin were different from spontaneous control cycles. There was no difference in the expression of alpha1, alpha v, and alpha4 between the groups studied. CONCLUSION(S): The administration of clomiphene produces aberrant endometrial beta3 integrin expression in conjunction with a failure in the down-regulation of PR during the window of implantation in a significant number of normo-ovulatory women, notwithstanding the higher plasma P levels. Therefore, CC might affect the expression of endometrial receptivity markers.     

Effects of clomiphene citrate on the endometrium of regularly cycling women

OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium of regularly cycling women. DESIGN: Prospective, controlled study. SETTING: Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. PATIENT(S): Thirty healthy, regularly cycling, female volunteers. INTERVENTION(S): All volunteers were studied for two consecutive cycles, one control cycle and one CC-treated cycle. Clomiphene citrate (100 mg/d) was given on days 3-7 of the CC-treated cycles. Ultrasonography was performed daily to assess ovulation. Ultrasonography and endometrial biopsy were performed, and blood samples were obtained for determination of E2 and progesterone levels 7 days after ovulation in both the control and CC-treated cycles. MAIN OUTCOME MEASURE(S): Histologic dating, morphometric analysis, and ultrasonographic appearance and thickness of the endometrium. RESULT(S): Histologic dating and ultrasonographic appearance and thickness of the endometrium were similar in the control and CC-treated cycles, but morphometric parameters were different. The number of glands per square millimeter and the mean diameter of the glands were lower in the CC-treated cycles than in the control cycles, but the number of vacuolated cells per 1,000 glandular cells was higher. CONCLUSION(S): Clomiphene citrate has effects on the endometrium of regularly cycling women, as demonstrated by a reduction in glandular density and an increase in the number of vacuolated cells.     

Endometrial histology after first trimester spontaneous abortion

The endometrial histology after spontaneous abortion was investigated by performing an endometrial biopsy in the two menstrual cycles subsequent to miscarriage in 12 women. In the first cycle, 66% (8/12) of the biopsies had the following abnormalities: (1) proliferative endometrium (n = 4), (2) proliferative glands and decidualized stroma (n = 1), (3) endometritis (n = 1), and (4) luteal insufficiency (n = 2). In the second cycle, 20% (2/10) of the biopsies demonstrated luteal insufficiency. Forty-five percent (10/22) of the first two cycles after spontaneous abortion demonstrated abnormal endometrial histology, with the first appearing more abnormal than the second (P = 0.06). Two conceptions occurred during the study period; both were uneventful term pregnancies. These findings suggest that a large proportion of the first two menstrual cycles after spontaneous abortion and curettage are abnormal, with the first cycle being more frequently abnormal than the second.     

Comparative morphometric study of the endometrium, the fallopian tube, and the corpus luteum during the postovulatory phase in normally menstruating women

OBJECTIVE: To compare function and histologic structure of the corpus luteum (CL) to the morphology of the endometrium and the fallopian tube in normally menstruating women. DESIGN: Circulating steroid and luteinizing hormone (LH) levels were compared with CL steroid production in vitro and the histology of CL, endometrium, and the fallopian tube at four stages of the postovulatory phase (days LH +/- 0/LH+3, LH+4/LH+7, LH+8/LH+11, LH+12/onset of menstruation). SETTING OF PATIENTS: The study included 28 volunteers with proven fertility undergoing surgical sterilization timed in relation to the LH surge. INTERVENTIONS: Blood and urine samples for LH, progesterone (P), and estradiol assessment were obtained before (simultaneously with ultrasound examinations), during, and after operation. Biopsy specimens from CL, endometrium, and fallopian tube were taken at the surgical sterilization and subjected to morphometric analyses. MAIN OUTCOME MEASURES AND RESULTS: Significant correlation was found between the endometrial dating and the LH surge (r = 0.923) and between the dating of the endometrial and CL biopsies (r = 0.918). A significant correlation (P less than 0.01) existed between circulating P levels and two endometrial indices; the number of vacuolated cells (LH+4/LH+7) and the glandular diameter (LH+8/LH+11). CONCLUSION: In normally menstruating women, the endometrial biopsy is likely to closely gauge the CL activity provided the biopsy is timed in relation to the LH surge.     

促排卵治疗对多囊卵巢综合征患者子宫内膜整合素αv,β3表？…

目的 了解促排卵药物对多囊卵巢综合征（ＰＣＯＳ）患者黄体中期子宫内膜整合素αｖ、β３表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术对２２例正常妇女、４０例无排卵ＰＣＯＳ患者促排卵治疗后黄体中期的子宫内膜整合素αｖ、β３进行测定。结果正常妇女子宫内膜整合素αｖ、β３表达在“着床窗口期”呈现强阳性;而氯米芬（ＣＣ）及绝经期促性腺激素（ｈＭＧ）抑制αｖ、βｂ的表达,使其表达呈弱阳性;而促性腺素释     

Induction of luteal phase defect with clomiphene citrate

The effect of clomiphene citrate and progesterone on luteal function in infertile women was studied. Endometrial biopsies were performed in 103 women immediately prior to menstruation. Group 1 (n = 62) had secretory endometrium with a histologic lag time of ≥48 hours with respect to the subsequent menses, that is, luteal phase defect. Group 2 (n = 10) had normal histologic characteristics of the secretory phase. Group 3 (n = 31) had anovulatory endometrium. The last group was subdivided into those with polycystic ovary syndrome (n = 9) and those without the characteristic gonadotropin pattern of polycystic ovary syndrome (n = 22). Clomiphene citrate at doses of 50 to 250 mg daily for 5 days was administered for induction of ovulation, timing of ovulation, or treatment of luteal phase defect. An endometrial biopsy was obtained after three ovulatory treatment cycles. Only one fourth of the women with prior luteal phase defect had normalization of the biopsy specimen with clomiphene citrate, while one half of those treated with progesterone had normal specimens. Half of the normally ovulating women had induction of a luteal phase defect with clomiphene citrate. Only women with polycystic ovary syndrome had consistently well-timed endometrial histologic features with clomiphene citrate therapy. Despite successful induction of ovulation, 16 of the other 22 previously anovulatory women had endometrial histologic findings compatible with luteal phase defect. Increasing the clomiphene citrate dosage was unsuccessful in improving endometrial maturation. These results suggest that the use of clomiphene citrate may be associated with a high rate of luteal phase defect induction, except among women with polycystic ovary syndrome. Clomiphene citrate, even at high doses, appears to be ineffective therapy for luteal phase defect.     

Delayed endometrial maturation in women with normal progesterone levels. The dysharmonic luteal phase syndrome

In 121 women attending the infertility clinic between 1978 and 1982, 127 cycles with luteal phases of 10 days or more were investigated by a complete basal body temperature (BBT) chart, three plasma progesterone assays taken between 11 and 4 days before menses, and a dated endometrial biopsy (EB) taken at the time of the last blood sample. All parameters were normal in 78 women (64.4%) categorized as group I 'normal luteal phases (NLP)'. There were some discordances between the three parameters in the remaining 43 women: 8 had normal BBT but low progesterone levels and delayed EB. They form group II 'inadequate luteal phases'. 29 women (23.9%) had delayed EB despite normal progesterone levels: forming group III 'dysharmonic luteal phases (DLP)'. 6 women had advanced EB and normal progesterone levels: group IV. Apart from endometrial maturation, there was no difference between NLP and DLP, neither in clinical parameters (length of the follicular phase, date and duration of the thermal shift, length of the luteal phase), nor in progesterone levels. Fertilization occurred in four DLP biopsied cycles: pregnancies went normally to term, giving birth to normal babies. Therefore, the DLP syndrome, characterized by normal midluteal progesterone levels and a delayed endometrial development, is not incompatible with normal nidation and gestation.     

Presence of corpus luteum as evidence of ovulation in women treated with low doses of chlormadinone acetate

50 women under continuous treatment for 1-31 months with 500 mcg chlormadinone acetate daily were studied. Culdoscopy was performed between Day 14 and 23 of their menstrual cycles. A corpus luteum was thought to be observed in 37 cases. In 18 with suspected corpus luteum a wedge resection of the ovary was done. Examination of patients 10 days after operation revealed no complications. In 4 cases subsequent culdoscopic examinations revealed no traces of biopsy damage. In 5 an endometrial biopsy was obtained the same day as the ovarian one or shortly thereafter. The 18 ovarian biopsies showed recent corpora lutea in 12, old corpus luteum in 1, follicular and theca-lutein cysts in 2, and normal follicles without corpus luteum in 3. Endometrial biopsies revealed 2 instances of normal secretory endometrium and 1 case of irregular endometrium with corpora lutea. Evidence of ovulation occurred in 70%. The reported pregnancy rate with low-dose progestogen therapy has been 3.7/100 years of woman exposure. The exact mechanism of contraception by chlormadinone acetate has not been determined.     

Efficacy of clomiphene citrate in the treatment of luteal phase deficiency: quantity versus quality of preovulatory follicles

We tested the hypothesis that the efficacy of clomiphene citrate (CC) in the treatment of luteal phase defect (LPD) is related more to the number of ovulatory follicles than to the quality of a single follicle. Eighteen ovulatory women with LPD as defined by endometrial biopsies that lagged behind chronological dates by at least 3 days on two separate menstrual cycles were studied. During the menstrual cycle before treatment and also during a treatment cycle (100 mg of CC, on days 5 to 9), we obtained an endometrial biopsy 9 to 12 days after ovulation. All biopsies were read in a blinded fashion by the same gynecological pathologist. During the treatment cycle, 10 women had more than one preovulatory follicle (greater than 15 mm, mean of three dimensions), while 8 had one preovulatory follicle. Luteal phase defect was corrected according to biopsy in 8 of the 10 women with more than one preovulatory follicle, but in only 2 of the 8 women with a single preovulatory follicle.     

Correlation of endometrial dating with luteinizing hormone peak

The number of days after ovulation in 11 normal menstrual cycles was determined by 2 methods: (1) dating of the histologic appearance of an endometrial biopsy and (2) daily serum LH measurement. The results of this study revealed that there was a significant correlation between these two techniques. These results substantiate the validity of histologic dating of the endometrium.