Luteal phase evaluation after clomiphene-chorionic gonadotrophin-induced ovulation

Fifty infertile patients treated with clomiphene and hCG for induction of ovulation were studied with plasma progesterone measurement and endometrial histology. Five patients (10%) presented defective endometria and low plasma progesterone in spite of biphasic BBT charts with normal luteal phase length. Forty-five patients (90%) had significantly higher plasma progesterone concentrations than those found in a control group of fertile women, but a defective endometrial secretory pattern occurred in 19 of these 45 patients (42.3%). These data suggest the need for monitoring the response to clomiphene by endometrial histology in addition to BBT and plasma progesterone, or for supplemental therapy to overcome the endometrial luteal phase deficiency in clomiphene-treated cycles.     

Luteal phase deficiency after completely normal follicular and periovulatory phases

Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal folliculogenesis included: a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases.     

Accuracy of basal body temperature for ovulation detection.

In 30 normally menstruating women, ages 19 to 41 (mean 24), gravida 0 to 5 (mean 0.7), basal body temperature (BBT) was correlated with serum luteinizing hormone (LH), progesterone, and estradiol or urinary estrogen levels assayed serially during one menstrual cycle. In 21 subjects (70%), a biphasic BBT correlated with an ovulatory hormonal pattern. Six women (20%) had a monophasic BBT but demonstrated a preovulatory estrogen peak, a midcycle LH surge, and a significant rise in serum progesterone levels during the luteal phase. The remaining three women (10%) showed anovulatory cycles (two women) or a deficient luteal phase (one woman) as determined by BBT and hormonal assays. The results indicate that in approximately 20% of ovulatory cycles the BBT failed to demonstrate ovulation.     

The "dysharmonic luteal phase" syndrome: endometrial progesterone receptor and estradiol dehydrogenase

The dysharmonic luteal phase (DLP) syndrome is defined by delayed endometrial maturation despite normal plasma progesterone (P) values. In ten patients with DLP the actual date of the endometrial biopsy, dated retrospectively, was 24.7 +/- 2.3 days, whereas the histologic date was 20.0 +/- 2.6 days. The concentration of cytosolic P receptor in DLP endometrium tended to be lower, whereas the concentration of nuclear receptor was significantly higher in DLP than in seven matched patients with normal luteal phases. Endometrial estradiol-dehydrogenase activities were identical in both groups. The DLP syndrome cannot be explained by a decreased sensitivity of the endometrium to P and is probably merely functional in nature.     

Luteal function after delayed ovulation

Thirty-three infertile patients presenting spontaneous ovulatory cycles with long follicular phases (greater than or equal to 20 days) underwent a luteal function evaluation by basal body temperature, plasma progesterone (P), estradiol, and prolactin determination, and endometrial biopsy study. An endometrial luteal phase deficiency (LPD) was detected in 13 patients (39.4%), although in 10 of them (77%) P levels were normal. This study shows a high incidence of endometrial LPD among cycles with delayed ovulation and that in cases of LPD related to abnormal folliculogenesis, the endometrium is a better indicator than plasma P.     

Improved prediction of postovulatory day using temperature recording, endometrial biopsy, and serum progesterone

The use of basal body temperature (BBT) recording and a single progesterone (P) level at the time of the endometrial biopsy in the late luteal phase improved our ability to predict the onset of the next menstrual period (NMP) and determine the postovulatory day (POD) in 124 regularly menstruating infertile women. We determined BBT shift using a microcomputer program, analyzed P levels by radioimmunoassay, and evaluated endometrial biopsies both prospectively (blinded) and retrospectively (with knowledge of the other variables). Serum P levels were within the normal range for the luteal phase and prospective and retrospective histological diagnoses closely agreed (82% within 2 days). The best correlation with the NMP was the BBT shift (r = 0.493) followed by P (r = 0.426) and prospective histologic dating (r = 0.390). Multiple regression analysis confirmed that use of all of the variables markedly improved the ability to estimate the POD (R2 = 0.51).     

Luteal phase in infertility: problems of evaluation

This study was undertaken to examine the endometrial data in 200 infertile women whose three progesterone estimations per cycle totaled over 15 ng/ml when taken from 11 to 4 days preceding menstruation. Forty-three patients (21.5%) showed defective endometria in two separate cycles. No difference was found when plasma progesterone concentrations in this group were compared with those of the remaining 157 infertile patients with normal endometria. Further, plasma progesterone in infertile women (both groups) was similar to a control group of 12 fertile women with normal secretory endometria. Endometrial biopsy is essential in the evaluation of luteal function in infertility and cannot be totally replaced by the use of plasma progesterone in three samples during the luteal phase since it failed to detect as much as 21.5% of abnormal secretory phases.     

Gonadotropin and ovarian hormone dynamics in luteal phase defects.

Blood samples were obtained during early follicular, periovulatory, and luteal phases in four women with out-of-phase endometrial biopsy specimens and four normal controls. In the study cycle, follicular development was evaluated and a late luteal phase endometrial biopsy was performed in each subject. Area under the luteal phase progesterone curve positively correlated with degree of maturity of the endometrial biopsy. Peak serum estradiol, maximum follicular diameter, and both immunoactivity and bioactivity of the preovulatory luteinizing hormone and follicle-stimulating hormone surges were similar in the luteal phase defect cycles as compared with normal cycles. Likewise luteinizing hormone bioactivity in the luteal phase of the luteal phase defect cycles was similar to that of normals. These data show that the immunoactivity and bioactivity of periovulatory and luteal phase gonadotropins may be normal in luteal phase defect cycles.     

Ultrasonographical assessment of follicular growth in delayed ovulation

The growth of the follicle was monitored in 61 subjects by ultrasonography and by the serial determinations of serum LH, FSH, estradiol (E2) and progesterone. All the subjects were judged to have normal luteal functions on the basis of their BBT patterns. The subjects were divided into two groups according to the length of their follicular phase: one with a follicular phase of 12--17 days (the control group, 39 cycles) and the other with a follicular phase of 18--26 days (the delayed ovulation group, 22 cycles). Ultrasonographically, the follicle grew slowly during the early follicular phase (slow growing phase), but began to grow more rapidly at 7 or 8 days before ovulation (rapid growing phase). In comparison with the control group, the slow growing phase was significantly prolonged in the delayed ovulation group. But in the length of the rapid growing phases and follicular growth rate, there were no significant differences between the two groups. In the serum levels of E2, LH, FSH and P, there were no significant differences between the two groups.     

Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists

OBJECTIVE: To evaluate the endometrium obtained during the luteal phase of controlled ovarian hyperstimulation (COH) cycles utilizing gonadotropin-releasing hormone (GnRH) antagonists, and to compare these findings with those obtained in cycles utilizing a GnRH agonist and with artificial cycles among recipients. DESIGN: Prospective evaluation of oocyte donors. SETTING: University-based in vitro fertilization (IVF) center. PATIENT(S): Fifteen oocyte donors undergoing standard COH were enrolled in 1 of 3 COH groups, and 40 recipients of oocyte donation were used as a control group. INTERVENTION(S): Controlled ovarian hyperstimulation and endometrial biopsy. MAIN OUTCOME MEASURE(S): Histological dating of endometrial biopsies, serum estradiol (E(2)) and progesterone levels. RESULT(S): On the day of oocyte retrieval, endometrial maturation was advanced by an average of 5.8 +/- 0.4 days in the antagonist group and 5.9 +/- 0.7 days in the agonist group. This advancement persisted on day 7 postoocyte retrieval. Serum progesterone levels were elevated before human chorionic gonadotropin (hCG) administration, but remained similar in both groups. CONCLUSION(S): Controlled ovarian hyperstimulation is associated with elevated progesterone levels in the late follicular phase and accelerated endometrial maturation in the subsequent luteal phase. No significant differences exist between preretrieval serial serum progesterone levels and luteal phase endometrial histology between cycles utilizing GnRH agonists or antagonists.     

Follicular phase treatment of luteal phase defect with follicle-stimulating hormone in infertile women

Fifteen infertile women diagnosed by endometrial dating to have a luteal phase defect were treated with human pituitary follicle-stimulating hormone (hFSH) for 45 cycles. Human follicle-stimulating hormone was administered intramuscularly in a dose of 50 IU/day (group 1) for 35 cycles and 100 IU/day (group 2) for ten cycles from either the third or fifth day of the cycle for five days. Plasma estrogen was measured daily during drug injection. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation by basal body temperature during 11 pretreatment control cycles and 39 treatment cycles. Endometrial biopsies were performed on the seventh day after ovulation. The daily estrogen levels increased gradually during hFSH treatment. There was no significant difference between the two dosage groups. The mean progesterone levels were: 1) significantly (P less than .02) greater in the treatment cycles than in the control cycles, 2) significantly (P less than .05) greater in the pregnancy cycles than in the nonpregnancy cycles, 3) significantly (P less than .01) greater in the cycles with normal endometrial dating than in the cycles with abnormal endometrial dating after treatment, and 4) significantly (P less than .05) greater in group 1 than in group 2. After treatment, the endometrial biopsy specimens were improved to normal in 20 of 38 cycles. Five patients became pregnant during the treatment. The authors have concluded that hFSH may be useful in treatment of luteal phase defect.     

不明原因不孕患者着床窗期子宫内膜形态结构与性激素及其受体表达

目的:研究着床窗期子宫内膜形态结构与性激素及其受体表达判断不明原因不孕患者的子宫内膜条件及黄体功能。方法:活检不明原因不孕55例及正常生育16例着床窗期子宫内膜行组织学天数及组织学分型;内膜扫描电镜观察胞饮突。检测黄体功能缺陷8例及子宫内膜反应不良6例着床窗期内膜性激素及其受体。结果:不孕组内膜的发育同步率(63.6%)明显低于正常生育组(93.8%),差异有统计学意义(P<0.05)。不孕组子宫内膜胞饮突数量少,且发育明显滞后于正常生育组。黄体功能缺陷患者着床窗期子宫内膜孕激素受体表达与正常生育组无统计学差异(P>0.05);子宫内膜反应不良患者孕激素受体表达明显低于正常生育组,差异有统计学意义(P<0.05)。结论:着床窗期子宫内膜发育同步性差,内膜容受性欠佳可能是部分不明原因不孕的病因之一。鉴别由黄体功能缺陷抑或子宫内膜反应不良引起的分泌期子宫内膜发育不良,是临床选择治疗方案的关键。     

Salivary progesterone as an index of the luteal function

Salivary progesterone (SP) is proposed as a useful index for estimation of luteal function. In 32 normal luteal phases with in-phase endometrial biopsies, the luteal SP assayed three times between 11 and 4 days before menses correlated significantly with the matched plasma P (PP) values and the ratio of SP to PP X 100 = 1.02. In 19 disharmonic luteal phases, a syndrome characterized by retarded endometrial development and apparently normal corpus luteum function, SP and PP were both in the normal range. In five conception cycles, SP and PP correlated significantly and increased during the evolution of the corpus luteum of pregnancy. In four cycles of luteal insufficiency, P concentrations were lower than normal in saliva as well as in plasma.     

Optimal features of basal body temperature recordings associated with conceptional cycles

Oral basal body temperature (BBT) recordings of 46 women that conceived by donor insemination and who had midcycle monitoring of luteinising hormone (LH) were analysed to establish features associated with an optimal cycle. All cycles exhibited a biphasic temperature shift associated with the follicular (mean + SD, 36.5 degrees C +/- 0.22) and luteal phases (36.8 degrees C +/- 0.19). Whilst a mean body temperature rise occurred on Day +1 when all cycles were analysed, individual patterns were seen at ovulation including no change or a decrease in BBT between Day 0 and Day +1. The BBT of the postovulatory phase was stable and only 4.5% of the 644 observations made showed a change of more than 0.2 degrees C from day to day. It was concluded that the BBT charting has limitations when used to recognize the day of ovulation, and that some variable patterns of the early luteal phase are consistent with conception. Finally, optimal luteal phases demonstrated remarkable stability.     

Luteal phase deficiency: ultrasonic and biochemical insights into pathogenesis

Summary. Serial ovarian ultrasound and daily assessments of plasma concentrations of pituitary and ovarian hormones were used to investigate ovarian function in 175 women with unexplained infertility. Their endocrine and ultrasound profiles were compared with similarly derived data from 43 normal volunteers. Fifty-one (29·1%) of the study group showed subnormal luteal phase rises in progesterone concentrations, described as poor progesterone surge (PPS) cycles. Within this group, 23 women (45·1%) demonstrated luteal cyst formation, a pattern not seen in any of the control cycles. High concentrations of follicle stimulating hormone (FSH) and reduced concentrations of oestradiol (E2) were observed in the follicular phases of the PPS cycles suggesting that the phenomenon is a product of abnormal follicular metabolism. An association of PPS with infertility exists, perhaps related to a combination of disturbances in the follicular micro-environment compromising oocyte quality, a failure of oocyte release, and impaired endometrial receptivity.     

Prolactin in the evaluation of luteal phase in infertility

Hyperprolactinemia was detected in 15 of 130 infertile patients (11.5%) with regular menstrual cycles and no galactorrhea who underwent luteal phase evaluation by basal body temperature (BBT), plasma estradiol (E2), and progesterone (P) determination, and endometrial biopsy (repeated in a later cycle when the first was defective). Luteal phase length and plasma levels of P and E2 were similar in the hyperprolactinemic and normoprolactinemic patients. Moreover, a significantly higher incidence of inadequate luteal phase, histologically documented, was found in the normoprolactinemic group. It is concluded that the usefulness of plasma prolactin (PRL) determination in the evaluation of luteal function in infertility is scanty and that most histologically documented cases of luteal phase defects occur with euprolactinemia.     

黄体功能缺陷与子宫内膜效应不良患者的内分泌特征

目的：分析比较黄体功能缺陷（ＬＰＤ）和子宫内膜效应不良（ＩＥＲ）患者的内分泌特征。方法：采用放射免疫法和放射性配体饱和竞争、葡聚糖活性碳吸附分析法，测定ＬＰＤ、ＩＥＲ患者和月经周期正常者（对照组）的血清激素水平及同一月经周期子宫内膜组织中的雌、孕激素受体含量。结果：ＬＰＤ患者黄体期的雌、孕激素水平显著低于对照组（Ｐ＜０．００１），其子宫内膜雌、孕激素受体含量在整个月经周期中与对照组无差异（Ｐ＞０．１）；而ＩＥＲ患者整个月经周期的血清雌激素水平均低于对照组（Ｐ＜０．００１），但黄体期的血清孕激素水平与对照组无差异（Ｐ＞０．１），子宫内膜增生期的胞浆雌激素受体、胞核孕激素受体和整个月经周期的胞浆孕激素受体含量亦显著低于对照组（Ｐ＜０．００１，Ｐ＜０．００１，Ｐ＜０．０５）。结论：ＬＰＤ和ＩＥＲ是内分泌特征根本不同的两种情况，ＬＰＤ主要表现为黄体细胞分泌雌、孕激素功能下降，子宫内膜相应受体含量正常；ＩＥＲ则为整个周期的雌激素水平降低及相应受体合成障碍，而黄体分泌孕激素的功能正常。     

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.     

Clinical observations on LRH-A used for contraception by luteolysis in normal women--analysis of 88 cases]

88 healthy female volunteers, ages 17-42, with regular menstrual cycles entered into the trail with a new superactive stimulatory analos of the LRH-A (D-A1a6-EA10) -LH for contraception by luteolysis. The LRH-A was administered intranasally or intramuscularly (im) on days 6-8 following the LH peak/BBT temperature rise for 1-5 successive cycles. Group 1 consisted of 12 women who were given 1000 mcg LRH-A intranasally for 4 days; group 2 consisted of 18 women who were given a single dose of 200 mcg LRH-A im; group 3 had 34 women who were given 200 mcg im b. i. d. for 1 day; and group 4 had 24 women who were given 200 mcg im g.d. for 3 days. During the treatment cycles, no additional contraceptive was used. Luteolysis was defined as the reduction in plasma progesterone and estradiol levels and the shortening of the luteal phase associated with an infertile cycle. Luteolysis occured in 9 of 12 cycles in group 1 with no shortening of the luteal phase in 3 cycles; in 13 of 18 cycles in group 2 with no shortening of the luteal phase in 5 cycles; in 32 of 34 cycles in group 3 with no decline of progesterone in i cycles; in 115 of 120 cycles in group 4 with 5 pregnancies occurring. The results showed that treatment with LRH-A seemed to be more efficient when applies in twice a day or q.d. for 3-4 successive days as compared with a single dose. No severe side effects were observed durin treatment and apparently normal cycles occurred immediately after withdrawal of treatment. The above data indicate that an adequate dose of LRH-A can provide a fairly good luteolysis result in women at the midluteal phase. However, more extensive study is necesary before a long-term application of LRH-A for contraception by luteolysis can be considered practical.     

Transvaginal ultrasonic assessment of endometrial growth in spontaneous and hyperstimulated menstrual cycles

Endometrial thickness and reflectivity were assessed by transvaginal ultrasound in both spontaneous and hyperstimulated menstrual cycles. Two groups of women with ovulatory cycles were examined; women in group 1 had unexplained infertility and women in group 2 were having artificial insemination by donor because of reduced spermatogenesis; a third group (group 3) comprised women with tubal infertility undergoing hyperstimulation for in-vitro fertilization. There was no difference in endometrial thickness or reflectivity between the three groups. A basic pattern of endometrial appearance common to all cycles was found, consisting of hypoechoic, isoechoic and hyperechoic images, occurring in the early follicular, late follicular and luteal phases, respectively. In all three groups a positive correlation was found between proliferative phase plasma oestradiol concentration and endometrial thickness. Group 1 r = 0.403, P less than 0.01; group 2 r = 0.439, P less than 0.01; and group 3 r = 0.617, P less than 0.01. There was a progressive increase in endometrial growth throughout the normal cycle until a plateau was reached 5 days after the LH surge. This pattern was also seen without acceleration of the process in hyperstimulated cycles, despite supranormal levels of oestrogen. Assessment of endometrial thickness is not a useful variable in monitoring hyperstimulated cycles. No aberrations of endometrial growth or pattern were observed in the women with unexplained infertility.