Control of progesterone and inhibin secretion during the luteal phase in the macaque

We investigated the temporal relationship between serum concentrations of progesterone and immunoreactive inhibin after treatment with an LHRH antagonist ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] -LHRH), during the mid-luteal phase in the macaque. Further, in an attempt to obtain a model of transitory suppression of luteal function, the effect of treatment with the LHRH antagonist for 1, 2 or 3 days during the mid-luteal phase on serum concentrations of progesterone and immunoreactive inhibin was compared. Differences in the pattern of decline of the two hormones were observed. Progesterone concentrations fell by 6 h after antagonist administration while inhibin was not significantly suppressed until 48 h. Treatment with three injections of LHRH antagonist caused a sustained suppression of luteal function as shown by low serum concentrations of progesterone and inhibin. Recovery of progesterone and inhibin secretion was observed in two out of six macaques treated with two injections of antagonist and in three out of six treated with a single injection. Therefore, with the regimens of LHRH antagonist which we employed this approach was not conducive to obtaining a reliable transitory suppression of luteal function. To elucidate further the gonadotrophin control of inhibin, six macaques were treated with three injections of the LHRH antagonist to induce a permanent suppression of luteal function but received concomitantly either human chorionic gonadotrophin (hCG) or human FSH daily for 5 days (n = 3 per group). FSH failed to prevent the antagonist-induced fall in progesterone and inhibin while hCG treatment completely reversed the inhibitory effects of the LHRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)     

The source of pulsatile secretion of progesterone during the human follicular phase.

This study was designed to establish the normal pattern of serum progesterone and the origin of its secretion during the follicular phase of the normal menstrual cycle. In the first study, 12 normal women were studied on 3 occasions each at different times during a single follicular phase. Serum samples were collected every 10 min over 8 h, for 6 h before and 2 h after an injection of naloxone (5 mg iv). The mean serum progesterone remained constant (0.9 nmol/L) across the follicular phase until just before ovulation; individual subjects showed pulsatility of progesterone (1-6 pulses/6 h) but there was no relationship of this to LH pulsatility and no variation of progesterone pulsatility across the follicular phase. Naloxone caused an increase in the mean serum progesterone in the early follicular phase to 1.9 +/- 0.7 nmol/L and in the mid and late follicular phase to 2.1 +/- 0.7 nmol/L and 3.4 +/- 2.5 nmol/L, respectively. The second study was performed to assess the contribution of the residual corpus luteum and the developing follicle to the pulsatile secretion of progesterone. Seven anovulatory women with low levels of serum LH and absent LH pulsatility were studied before and after clomiphene (100 mg/day for 5 days) by collecting blood samples every 15 min for 6 h before GnRH (10 mg iv) and for 2 h afterwards. The anovulatory women had comparable mean serum concentration of progesterone (0.9 +/- 0.5 nmol/L) to normal women and similar frequency of progesterone pulsatility (2.1 +/- 1.1 pulses/6 h). After administration of clomiphene, there was no significant change in progesterone pulsatility (1.7 +/- 1.0 pulses/6 h) despite a substantial increase in LH pulsatility (from none to 3.0 +/- 1.0 pulses/6 h). There was no significant increase in serum progesterone after clomiphene or GnRH which both caused a substantial increase in serum LH. The third study involved eight normal women studied before and after treatment with dexamethasone (2 mg/day for 2 days) to assess the adrenal component of progesterone secretion. Blood samples were collected every 10 min for 6 h before and 2 h after naloxone (5 mg iv). Dexamethasone reduced serum progesterone to below assay sensitivity (less than 0.2 nmol/L) and obliterated progesterone pulsatility. The increase in serum progesterone and cortisol induced by naloxone was blocked by dexamethasone; the naloxone-induced rise of serum LH was not affected by dexamethasone. We conclude that neither the preceding corpus luteum nor the developing follicle are important contributors to the serum concentration of progesterone during the normal follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute effects of progesterone and the antiprogestin RU 486 on gonadotropin secretion in the follicular phase of the menstrual cycle

Considerable controversy still exists concerning the role of progesterone in the initiation of the midcycle gonadotropin surge in humans. We, therefore, carried out a prospective randomized study to determine the potential of progesterone to initiate a gonadotropin surge and the acute effects of a potent progesterone antagonist (RU 486) on follicular phase gonadotropin secretion in normal women. The women underwent frequent blood sampling for 4 in the midfollicular (day 6) or late follicular phase (day 10). They then received either progesterone (10 mg, im) or RU 486 (10 or 100 mg, orally), and blood sampling was continued for an additional 8 h. Four women received each of the drug regimens in the early follicular phase, and four received each regimen in the late follicular phase. Two additional women were studied as control subjects at each stage of the cycle. Progesterone administration in the mid- and late follicular phases resulted in an acute increase in plasma LH and FSH concentrations, and the increases correlated with the base line plasma estradiol concentrations (P less than 0.05). In contrast to progesterone, the women who received RU 486 in the mid- and late follicular phases had a reduction in plasma LH and FSH concentrations after drug administration. The response in the mid-follicular phase was considerably less than that in the late follicular phase, and the extent of the response correlated with the baseline plasma estradiol concentrations (P less than 0.005). The changes were similar in response to both RU 486 doses. We conclude that progesterone can initiate a gonadotropin surge in the late follicular phase of the menstrual cycle. The inhibitory effect of the progesterone antagonist RU 486 suggests that a positive feedback mechanism involving progesterone may be influential some time before the surge onset.     

Inhibin secretion by the sheep ovary during the luteal and follicular phases of the oestrous cycle and following stimulation with FSH

The secretion of oestradiol and inhibin were measured during the follicular and luteal phase of the cycle by a sensitive bioassay using sheep pituitary cells in culture in four ewes in which the left ovary had been autotransplanted to the neck. On day 12 of the cycle, premature luteal regression was induced with an injection of 100 micrograms cloprostenol (prostaglandin F2 alpha analogue; PG) and ovarian venous blood was collected every 4 h for 72 h. These same four ewes were infused in the ensuing cycle with NIH-oFSH-S14 at 10 micrograms/h for 48 h immediately after an injection of PG and sampled as above. During the luteal phase (-2 h before PG) both in the control and FSH-infused cycles the inhibin secretion rate (SR) was 27-45 units/min. After PG injection, the inhibin SR declined with time to reach 3.6-5 units/min at the onset of the LH surge (60 h after PG) in the control cycle. In contrast, in the following cycle infusion of FSH after PG injection caused a slight increase in the inhibin SR which then remained raised at 42-50 units/min for up to 60 h after PG. In the late follicular phase the oestradiol SR was greater in the FSH-infused than in the control cycles, indicating multiple follicular development. In the FSH-infused cycle the preovulatory surges of LH and FSH were markedly attenuated. These data demonstrate that (1) inhibin SR is high during the luteal phase suggesting that the sheep corpus luteum secretes inhibin, (2) in the control cycle inhibin SR declines during follicular maturation at a time when oestradiol SR is increasing but FSH levels are decreasing, and (3) exogenously administered FSH stimulates the secretion of inhibin from the ovary during the follicular phase.     

The dependence of estradiol and progesterone reception in the endometrium on its histological structure in women with the syndrome of luteal phase failure

A study of the level of the sex steroid receptors in the endometrium of women with the syndrome of insufficiency of the luteal phase of the cycle (ILP-syndrome) has shown that disorders of receptor processes affect, first of all, progesterone receptors. An increase in a degree of a delay of endometrial development was accompanied by a rise of the level of progesterone in the endometrium which depended on the estradiol-progesterone ratio in the circulation, detectable on the 20th day of the menstrual cycle. The ILP-syndrome is characterized by the sufficient induction of progesterone receptors at the end of the proliferative--the beginning of the luteal phase of the cycle and by their insufficient inhibition with a low level of progesterone in the middle of the luteal phase. Insufficient synthesis of receptors as a result of sharp hypoestrogenemia is less frequent. The primary affection of the receptor apparatus as a cause of the ILP-syndrome against a normal hormonal background in the examinees was undetectable.     

Prolactin secretion and corpus luteum function in women with luteal phase deficiency

Luteal phase deficiency (LPD) as a clinical infertility problem is considered to have a heterogeneous etiology. Hyperprolactinemia has long been considered a causative factor of LPD. In this context we investigated PRL secretion in 18 women with LPD. All of the subjects were infertile with 2 out of phase (greater than 2 days) endometrial biopsies; 10 of the women also had daily blood samples, this latter subgroup had significantly decreased integrated luteal phase progesterone (P) levels compared to normal women with in-phase biopsies. PRL secretion was investigated as follows: 1) daily blood levels; 2) pulsatile secretion patterns in 3 cycle phase [early follicular (12 h); late follicular (12 h); midluteal (24 h)], 3) LH-PRL coupling, and 4) nocturnal patterns. Results were compared to findings in 36 normal women. The mean daily levels of PRL over the menstrual cycle were not different between the two groups (LPD, 12.1 +/- 1.5; normal, 13.8 +/- 0.8 microgram/L; P = 0.3). There was no correlation between luteal phase integrated P and PRL levels for either group. There was a small difference in the PRL pulse amplitude in the early follicular phase between the LPD and normal women (2.6 +/- 0.3 vs. 5.5 +/- 1.3 micrograms/L; P less than 0.05). There were no significant differences between groups in PRL pulse frequency or mean level during the 12 or 24 h in any cycle phase. There was an equivalent amount of LH-PRL pulse coupling in both groups in all three cycle phases. Diurnal and nocturnal PRL secretion was studied by breaking the 24 h data (midluteal) into day (0700-2300 h) and night (2300-0700) segments. Mean PRL levels were higher at night in both groups (LPD, 15.9 vs. 12.6; normal, 15.4 vs. 9.3 micrograms/L; P less than 0.05), as expected. There were no differences in nocturnal PRL secretory patterns between the two groups. In summary, we have serious reservations whether abnormalities in PRL secretion are a common or integral part of the pathophysiology of LPD. From previous work we know these subtle abnormalities in PRL secretion in LPD are associated with definite abnormalities in gonadotropin secretion. We believe these gonadotropin abnormalities are probably more significant in terms of decreased P secretion.     

Characterization of profiles of salivary progesterone concentrations during the luteal phase of fertile and subfertile women

Salivary progesterone concentrations were measured in daily samples collected between 08.00 and 09.00 h throughout the menstrual cycle of women with a history of fertility. The luteal-phase salivary progesterone profiles in these normally menstruating, healthy women were characterized using a computer program based on a cumulative sum procedure. This method of statistical analysis led to the development of a 'progesterone boundary diagram', the inner and outer domains of which distinguished between the profiles of salivary progesterone considered compatible with fertility, and those observed in subfertile women attending an infertility clinic.     

Gonadotropic stimulation of inhibin secretion by the human ovary during the follicular and early luteal phase of the cycle

We studied the pattern of secretion of inhibin bioactivity from the ovary into peripheral blood during the follicular and early luteal phase of the menstrual cycle in women receiving gonadotropin therapy. Multiple follicular development was stimulated in 5 women undergoing in vitro fertilization and embryo transfer for tubal infertility using three different treatments designed to vary the concentration of FSH and LH (14 cycles). The women received clomiphene citrate (150 mg/day) from days 2-6 alone or supplemented with either exogenous human menopausal gonadotropin (28 IU/3 h) or pure FSH (28 IU/3 h) from day 6 until the day of follicle aspiration. Inhibin concentrations increased 10-fold in parallel with those of estradiol, from 0.2-0.3 U/mL on day 2 (before the onset of treatment) to 4-5 U/mL on day 14 of the cycle (time of the peak LH level). Coincidental to the LH surge, the inhibin concentration declined 2- to 3-fold before increasing again early in the luteal phase. The concentration of inhibin was higher in the gonadotropin-treated group (clomiphene plus human menopausal gonadotropin/FSH) than in the group treated with only clomiphene during the follicular phase. The number of follicles stimulated was significantly higher (P less than 0.001) in the group given exogenous gonadotropins [4.8 +/- 0.4 (SE)] than in the clomiphene alone group (2.2 +/- 0.4). These data strongly suggest that both the Graafian follicles and the corpus luteum secrete inhibin, which together with estradiol and progesterone may play a role in the regulation of FSH secretion during the luteal phase.     

Decreased progesterone receptor isoform expression in luteal phase fallopian tube epithelium and high-grade serous carcinoma

We previously reported that BRCA1/2-mutated fallopian tube epithelium (FTE) collected during the luteal phase exhibits gene expression profiles more closely resembling that of high-grade serous carcinoma (HGSC) specimens than FTE collected during the follicular phase or from control patients. Since the luteal phase is characterised by high levels of progesterone, we determined whether the expression of progesterone receptor (PR) and PR-responsive genes was altered in FTE obtained from BRCA mutation carriers during the luteal phase of the menstrual cycle. RT-qPCR confirmed a decreased expression of PR mRNA in FTE during the luteal phase relative to follicular phase, in both BRCA1/2 mutation carriers and control patients. Immunohistochemistry using isoform-specific antibodies confirmed a low level of both PR-A and PR-B in HGSC and a lower level of staining in FTE samples obtained during the luteal phase compared with the follicular phase. No significant difference in PR-A or PR-B staining was found based on patient BRCA mutation status. Analysis of our previously reported gene expression profiles based upon known PR-A- and PR-B-specific target genes did not partition samples by BRCA mutation status, indicating that overall FTE PR response is not altered in BRCA mutation carriers. HGSC samples grouped separately from other samples, consistent with the observed loss of PR expression. These findings indicate no overall difference in PR signalling in FTE as a function of BRCA mutation status. Thus, the molecular similarity of BRCA1/2-mutated luteal phase FTE and HGSC likely results from an altered response to luteal phase factors other than progesterone.     

Plasma lipid and lipoprotein levels during the follicular and luteal phases of the menstrual cycle

Estrogen levels are higher during the luteal compared with the follicular phase of the menstrual cycle. It was hypothesized that the luteal compared with the follicular phase has a lipid and lipoprotein profile associated with decreased coronary heart disease (CHD) risk. This was tested using well-defined data from healthy, well-characterized premenopausal Caucasian women under very controlled metabolic conditions. The percent differences in lipid, lipoprotein, and sex hormone levels between the follicular and luteal phases were estimated using generalized estimating equations after adjusting for age, body mass index, calendar time, and season. The low-density lipoprotein cholesterol (LDL-C) level was 6.2% lower (P = 0.015), and the total cholesterol/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were 5.1% (P = 0.0006) and 8.4% (P = 0.002) lower, respectively, during the luteal phase. Levels of estradiol and other estrogens were significantly higher (by>100% each; P < 0.0001 in all cases) in the luteal phase. These findings support the study hypothesis. Fluctuations in levels of LDL-C and the total cholesterol/HDL-C and LDL-C/HDL-C ratios between menstrual cycle phases need to be considered in the screening and medical monitoring of premenopausal women, especially those with borderline levels. Although small, such fluctuations may prove to be clinically significant in the long run. Studies involving premenopausal women need to more clearly define and validate menstrual cycle phase in the design and interpretation of study results.     

Altered postural control during the luteal phase in women with premenstrual symptoms

The purpose of this study was to investigate postural control in women with and without premenstrual symptoms (PMS) in three hormonally verified phases of the menstrual cycle. Thirty-two women were recruited to participate in the study and 25 of these women were included in the results. Menstrual cycle phases were determined by sex hormone analyses in serum and LH detection in urine. A prospective rating of PMS was used to divide the subjects into two groups: one with PMS (cyclic) and one without (non-cyclic). For measurement of postural control, subjects stood on a force platform (AMTI) in two-legged stance (eyes open and closed) and one-legged stance (eyes open and closed). There were no significant differences in the two-legged stance between the phases of the menstrual cycle or between groups. In one-legged stance with eyes open, there was a significant increase in postural displacement in the mid-luteal phase in the cyclic group, but no differences were detected between phases in the non-cyclic group. These findings may be related to the previously reported increased injury rate and psychomotor slowing in the luteal phase in women with PMS.     

Relation of circulating estradiol and progesterone to gonadotropin secretion and estrous cyclicity in aging female rats

The progressive cessation of regular ovulatory function in aging female rats is preceded by a significant decrease in the magnitude of the proestrous LH surge during regular estrous cycles. However, our recent study has demonstrated that normal LH secretion and regular estrous cycles can be maintained for an extended period of time in aging females housed with fertile males and allowed to undergo repeated pregnancies. Since progesterone (P) secretion is persistently increased in pregnant rats, the present study examined whether repeated increases in circulating progesterone accounted for these results. Starting at 8 months of age and continuing to 13 months, multiparous rats were grouped and treated as follows: controls: females were housed five per cage; mated: five females were housed with one fertile male and allowed to undergo repeated pregnancies; and P-implanted: females were housed five per cage and implanted sc with Silastic capsules containing P for 3 of every 4 weeks. During the 4.5 months of study, serum concentrations of estradiol (E2) in the P-implanted rats remained between 13 and 27 pg/ml, similar to levels in pregnant females (8-26 pg/ml) of the mated group. These E2 values were less than the preovulatory increase in serum E2 on proestrus (mean +/- SE, 56 +/- 10 pg/ml) in cyclic control females. In contrast, serum P values were persistently elevated in both the pregnant and the P-implanted rats, although the values in the latter (27-55 ng/ml) were about one third to one half of those in the former group (117-125 ng/ ml). All treatments were stopped at 13 months of age, and estrous cycle patterns were determined thereafter. Between 13 and 17 months of age, the percentages of regularly cycling rats were significantly (P less than 0.01) greater in the mated group (50%, 36%, and 15% at 13, 15, and 17 months, respectively) than in the control group (23%, 20%, and 9%, respectively). During this same period, 50% of the females from the P-implanted group continued to display regular cycles. By the age of 11 months, 8 of 21 untreated retired breeder females exhibited attenuated LH surges on proestrus and subsequently ceased to display regular estrous cycles within 2 months, whereas the other 13 rats showed normal LH and FSH surges and continued to maintain regular cycles. In contrast to these, aged female rats from the previously mated (15-month-old) and the P-implanted (19-month-old) groups exhibited normal profiles of proestrous LH and FSH surges during regular estrous cycles.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nocturnal slowing of pulsatile luteinizing hormone secretion in women during the follicular phase of the menstrual cycle

The gonadotropin secretion pattern in normal reproductive age women (n = 5) was evaluated for the presence of a circadian rhythm. The women volunteered for a series of 24-h admissions in different phases of their menstrual cycles (early follicular, late follicular, and midluteal). Plasma LH and FSH levels were determined by RIA in blood samples drawn through indwelling venous catheters at 20-min intervals throughout a normal 24-h sleep-wake cycle. The gonadotropin secretory pattern was subjected to cosine analysis for identifying rhythmicity. The LH interpulse interval fluctuated with a significant 24-h rhythm during the early follicular phase in four of the five women. The maximum interpulse intervals occurred during the early morning between 0100 and 0500 h (mean, 0250 h), with a corresponding increase in LH pulse amplitude occurring within the same time interval (mean, 0320 h). We found no consistent 24-h rhythms in overall mean plasma LH levels during any phase of the menstrual cycle, nor did we find a significant rhythmicity in either LH interpulse interval or LH pulse amplitude during the late follicular or luteal phase. These results demonstrate that the LH pulse-generating system is frequency modulated on a circadian basis during the early follicular phase of the human menstrual cycle.     

Changes in FSH and the pulsatile secretion of LH during treatment of ewes with bovine follicular fluid throughout the luteal phase of the oestrous cycle

Treatment of Damline ewes with twice-daily i.v. injections of bovine follicular fluid during the luteal phase for 10 or 2 days before prostaglandin-induced luteolysis resulted in a delay in the onset of oestrous behaviour and a marginal increase in ovulation rate. During the treatment cycle, blood samples were withdrawn at 15-min intervals for 25 h from 08.00 h on days 1, 6 and 10 (day 0 = oestrus). At all three stages of the luteal phase, plasma FSH concentrations were suppressed relative to controls 3 h after the 09.00 h injection of follicular fluid and remained low until 06.00 h on the following day. In the 10-day treatment group LH pulse amplitude was significantly greater than that of controls on days 6 and 10. Pulse frequency remained high throughout treatment and was significantly higher relative to controls on day 10 despite normal progesterone levels. The results suggest that the higher pulsatile LH secretion during the luteal phase is due to reduced negative feedback effects of oestradiol occurring as a result of the follicular fluid-induced reduction in FSH.     

Elevations in unbound serum estradiol as a possible mechanism for inappropriate gonadotropin secretion in women with PCO

Twenty-three women considered to have polycystic ovarian disease (PCO) were studied in an effort to better understand the mechanism of inappropriate secretion (IGS) which is so characteristic of these women. Criteria for PCO included oligomenorrhea, infertility, an obesity index (ponderal index, PI) < 12, and an LH:FSH ratio > 3. The mean +/- SE weight and PI for this group were 175 +/- 7.5 lbs. and 11.2 +/- 0.2 respectively. Weight was not correlated with steroid levels in PCO or control women. The mean (+/- SE) of serum androgen concentrations (DHEA-S: 2.9 +/- 0.5 micrograms/ml; androstenedione: 2.6 +/- 0.3 ng/ml; and testosterone: 47 +/- 5 ng%) were all significantly higher than those in control women (p < .05). Total serum estradiol (E2) was comparable to those of controls in the follicular phase, while estrone (E1): E2 ratios averaged 2:1. Serum sex hormone binding globulin-binding capacity (SHBG-BC) averaged 56.8 +/- 4.2 nM which was significantly lower than that of controls (p < .05). The percent unbound E2 was significantly elevated in PCO (62% vs 37%). The mass of unbound E2 was also significantly higher in PCO women (40 +/- 3 pg/ml) than in controls (17 +/- 2 pg/ml) (p < .005). Serum LH:FSH ratios had a positive correlation with the relative and absolute concentration of unbound E2. In control women, unbound E2 correlated significantly with LH levels. This suggests that IGS characteristically found in PCO patients and exemplified by elevated LH;FSH ratios, is the result of the feedback response to elevated levels of unbound (i.e., biologically active) E2.     

The roles of estradiol and progesterone in decreasing luteinizing hormone pulse frequency in the luteal phase of the menstrual cycle

During the luteal phase of the menstrual cycle, plasma progesterone (P) and estradiol (E2) concentrations are elevated, and LH (and by inference GnRH) pulse frequency is slow. In contrast, LH pulse frequency increases during the early follicular phase when plasma E2 and P are lower. To examine the mechanism(s) responsible for the slower GnRH pulse frequency in the luteal phase, we maintained plasma P, E2, or both at midluteal concentrations from the midluteal phase to the time of the next early follicular phase and measured the effects on LH secretion. Thirteen normal women with regular menstrual cycles were studied during two or three cycles. Blood was obtained every 10 min during 10-h studies. Control cycle luteal and early follicular studies were followed by a second control study in the luteal phase of the treatment cycle. P (six women), E2 (seven women), or both (five women) then were given twice daily by im injection for 6-12 days until the day corresponding to the early follicular study of the control cycle (EF + P, EF + E2, or EF + E2 + P). A final study was performed 1 week after the injections were discontinued (F). LH pulse frequency was low in the midluteal phase [3.2 +/- 0.2 (+/- SE) pulses/10 h] and increased by the early follicular phase (8.0 +/- 0.8 pulses/10 h) in the control cycles. The increase in LH pulse frequency was not significantly inhibited by administration of P (6.7 +/- 0.7 pulses/10 h; EF + P). However, during both E2 alone and E2 + P, LH pulse frequency remained low (EF + E2, 3.6 +/- 0.8; EF + E2 + P, 2.0 +/- 0.7 pulses/10 h). The mean plasma FSH concentrations paralleled changes in LH pulse frequency, increasing from the luteal to the early follicular phase in the control cycles and during P injections and remaining low during E2 and E2 + P injections. We conclude that continued exposure to P alone does not maintain GnRH pulse frequency at midluteal phase values and that any effect of P requires the presence of E2. As E2 alone maintained lower LH pulse frequency, E2 may act directly to decrease the pulsatile GnRH secretion or it may potentiate the effects of low (less than 3.2 nmol/L) P concentrations.     

Correlation between endometrial biopsy and luteal phase plasma progesterone in women complaining for couple infertility

One hundred forty-three women complaining for couple infertility (more than 2 yr), were investigated for luteal phase deficiency (i.e. insufficient endometrial luteinization) by endometrial biopsy and serial determinations (in days -10, -7 and -4 respect the onset of the next menses) of plasma progesterone during luteal phase. One hundred-three women had the first endometrial biopsy in phase (IP), 36 had the biopsy "out of phase" (OOP). Among them 13 did not repeat endometrial biopsy, 12 had the second biopsy out of phase (and then classified as Luteal Phase Deficiency) and 11 had the second biopsy "in phase". Only the women affected by luteal phase deficiency had the plasma progesterone (mean of 3 samples) significantly lower than that of infertile women with normal endometrial luteinization. However the majority of the individual progesterone values of these two groups overlapped. The endometrial biopsy seems to be the most practicable method for investigating luteal phase deficiency in women complaining for couple infertility.