Ovulation stigma and concentration of progesterone and estradiol in peritoneal fluid: relation with fertility and endometriosis

The relationship between the presence or absence of an ovulation stigma and (1) the fertility status, (2) the incidence of endometriosis, (3) the concentration of progesterone and estradiol in the peritoneal fluid, and (4) the blood levels of luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol in 21 fertile and 45 infertile patients who underwent a laparoscopy in the early (n = 48) or late luteal phase (n = 18) was investigated. An ovulation stigma was observed in about half of the patients, irrespective of their fertility status (past and subsequent), the presence of endometriosis, or the time of the luteal phase. Progesterone and estradiol concentrations in the peritoneal fluid were highest in the early luteal phase, but they were not correlated with the presence or absence of an ovulation stigma. No significant differences were observed in peripheral hormone levels between women with and those without an ovulation stigma nor between women with high or low concentrations of progesterone in the peritoneal fluid. From the data, it is concluded that hormone assays are of no aid in the diagnosis of the luteinized unruptured follicle syndrome and that the absence of an ovulation stigma on laparoscopic examination cannot be equated with the luteinized unruptured follicle syndrome.     

Ovarian adhesions impair ovulation

The concentration of progesterone in peritoneal fluid, aspirated from the pouch of Douglas by laparoscopy, 72 hours after the peak of the luteinizing hormone in serum is believed to indicate whether the ovarian follicle has ruptured or not. Twenty six patients were studied. The volume of peritoneal fluid 72 hours after the peak of the luteinizing hormone was markedly decreased when bilateral ovarian adhesions were present. Progesterone concentrations, assayed during the early luteal phase in peritoneal fluid of women with bilateral ovarian adhesions, were significantly lower than in women with a corpus luteum presenting an ovulation stigma and even significantly lower than in those without ovulation stigma (luteinized unruptured follicle syndrome). The assay of progesterone in peritoneal fluid during the early luteal phase may be of value in women with ovarian adhesions.     

Protein, progesterone, and protease inhibitors in uterine and peritoneal fluids of women with endometriosis

This study was undertaken to determine whether women with endometriosis have altered protein, progesterone (P), and protease inhibitor concentrations in their uterine fluid and peritoneal fluid (PF) compared with controls at different phases of the menstrual cycle. Uterine flushings (UFs), PF, and blood were obtained during the follicular and luteal phases of the cycle from 29 normal women and 16 women who were diagnosed as having endometriosis. Protein content in UF did not change significantly throughout the cycle in either group. However, PF protein in patients with endometriosis was significantly (P less than 0.05) higher than in controls during the luteal phase. Total UF P was significantly (P less than 0.05) reduced in women with endometriosis during the late luteal phase. During the early luteal phase, trypsin inhibitory activity in UF from normal women was significantly (P less than 0.05) higher than at any other phase of the cycle, whereas inhibitory activity in UF from patients with endometriosis remained relatively constant. Patients with endometriosis had significantly (P less than 0.05) higher total activity in PF during the early luteal phase than did controls. These results indicate that women suffering from endometriosis have significantly lower levels of P and less protease inhibitor within their uterine cavity during the luteal phase of the cycle, and significantly higher concentrations of protein and protease inhibitor in PF during the luteal phase.     

Incidence, recurrence and treatment of the luteinized unruptured follicle syndrome

The frequency of the luteinized unruptured follicle (LUF) was determined in a population of 220 regularly cycling women, infertile for at least two years. Laparoscopy was performed during the very first days of the luteal phase. In 26 women without other demonstrable cause of infertility, a diagnosis of LUF was made based on the absence of an ovulation stigma and the low concentrations of progesterone (P) and 17 beta-oestradiol (E2) in peritoneal fluid (PF). Twenty of these 26 women underwent a culdocentesis 72-96 hours after the serum LH-rise in a following cycle. In 19 out of 20, low P and E2 concentrations in PF were again found, suggesting the recurrence of LUF. Subsequently, ovulation was induced with human menopausal gonadotrophins (hMG) alone (n = 4), or in combination with human chorionic gonadotrophin (hCG, n = 9). At carefully timed culdocentesis (at LH/hCG + 72-96 hours), P concentration in PF was high in the hMG-hCG treated women but remained low in those given hMG alone. The combination of hMG and hCG may be a valuable treatment of LUF.     

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.     

Luteal function following ovarian stimulation in rhesus monkeys for in vitro fertilization: atypical response to human chorionic gonadotropin treatment simulating early pregnancy

This study determined if corpora lutea of hyperstimulated cycles in rhesus monkeys could be "rescued" by the pregnancy signal, chorionic gonadotropin (CG), given at the typical time of implantation. At menses, female monkeys received human follicle-stimulating hormone (hFSH, 60 IU, days 1 to 6) followed by human menopausal gonadotropin (hMG, 60 IU hFSH/60 IU luteinizing hormone [hLH], days 7 to 9). On day 10, human chorionic gonadotropin (hCG) was given to mimic the LH surge. Nine days later, a regimen of daily increasing doses of hCG (15 to 360 IU twice a day) was initiated to simulate rescue of the corpus luteum in early pregnancy. Serum levels of progesterone (P) increased through day 5 of the luteal phase but then declined. Circulating levels of bioactive LH were significantly less on days 7 to 9 of the luteal phase than at this stage in the natural cycle. The hCG regimen extended (P less than 0.05) the luteal phase in five of six animals. The hCG treatment elicited a persistent increase (P less than 0.05) in circulating P levels, rather than a transient rise typical of normal or simulated pregnancy in natural cycles. The authors conclude that (1) corpora lutea of hyperstimulated cycles can respond to CG, but (2) there are differences in luteal function during both the luteal phase and simulated early pregnancy that may be due to inadequate luteal development or the abnormal gonadotropin milieu existing after ovulation or both.     

Oestradiol-17 beta and progesterone level changes in peritoneal fluid around the time of ovulation

In 15 women, peritoneal fluid was obtained by either culdocentesis (n = 20) or laparoscopy (n = 3), before (n = 9) and after (n = 14) ovulation. Ultrasound was used for ovulation detection. Before ovulation the mean oestradiol-17 beta level in plasma and peritoneal fluid was not essentially different; the mean progesterone level was significantly higher in peritoneal fluid. After ovulation both the mean oestradiol-17 beta and progesterone levels were significantly higher in peritoneal fluid than in plasma. In peritoneal fluid, there was a wide distribution of individual oestradiol-17 beta values before and after ovulation; no significant difference existed between the mean pre- and postovulatory oestradiol-17 beta level. More consistent changes were seen in peritoneal fluid progesterone levels; the mean level was significantly higher after ovulation. In three subjects, a low postovulatory progesterone level in peritoneal fluid was associated with a cystic luteal structure observed by ultrasound, suggesting a reduced leakage of fluid from the ovulation stigma.     

Luteal phase support with hCG does not improve fecundity rate in human menopausal gonadotropin-stimulated cycles.

The luteal phase of cycles stimulated with human menopausal gonadotropins (hMG) may be characterized by aberrant hormone levels, altered endometrial development, and shortened length. Luteal phase support with supplemental progesterone or hCG has been recommended to help correct these problems and thus improve pregnancy rates, but the efficacy of such regimens is controversial. Therefore, a randomized cross-over study was performed to evaluate the effects of luteal phase hCG administration on pregnancy rates during ovulation induction with hMG. Sixty-seven infertile women were randomly assigned to either group A (N = 33) or group B (N = 34). Non-treatment cycles (no luteal phase support) were alternated with treatment cycles, in which patients received 2500 IU hCG on the third, sixth, and ninth days after the ovulatory dose of 10,000 IU hCG. Patients in group A received supplemental hCG in odd-numbered cycles, whereas group B was given luteal support in even-numbered cycles. The mean number of cycles per patient was 2.2 and 2.3 for groups A and B, respectively. Analysis of 151 cycles revealed a cycle fecundity of 0.15 for 72 hCG-supported cycles, versus 0.13 for 79 nonsupported cycles (P = not significant). Midluteal progesterone levels were significantly higher in supported (45.6 ng/mL) versus unsupported cycles (31.9 ng/mL) (P less than .001). There were no significant differences in the mean peak estradiol levels in hCG-supported versus -unsupported cycles. We conclude that hCG support of the luteal phase is not routinely warranted in hMG-stimulated cycles.     

Serum gonadotropin and steroid patterns in early human gestation

Estradiol (E), progesterone (P), 17-hydroxyprogesterone (17-P), follicle stimulating hormone (FSH), luteinizing hormone-human chorionic gonadotropin (LH-HCG), and human placental lactogen (HPL) concentrations were measured in serum samples obtained daily from 3 women from the last menstrual period (LMP) throughout the 1st few months of gestation. Radioimmunassay of serum samples was used. FSH levels declined after implantation in 1 subject and remained unchanged in the others. HCG levels began to rise above luteal phase LH values 11-14 days after the midcycle LH peak. HPL became detectable 34-38 days after the LH peak. E levels rose steadily after the postovulatory nadir, increasing rapidly 4 weeks after the LH peak. Patterns of P and 17-P were similar initially; both rose after ovulation, remained elevated for several weeks, and then declined. About 11 weeks after the LMP, levels of P again increased whereas 17-P remained low. Single serum samples were obtained from an additional 158 gravid women 6-16 weeks after the LMP, and E, P, and 17-P were measured in each. Mean levels of E steadily increased and 17-P steadily decreased. Mean P dropped to a nadir at 9 weeks and rose therafter. Since the 17-P is mainly of luteal origin, these findings indicated that in normal pregnancy the corpus luteum has maximal activity for about 4 weeks after ovulation. Falling levels of P in the 3 weeks prior to increased trophoblastic production of this hormone may contribute to the cause of 1st trimester uterine bleeding in some women who have normal term pregnancies.     

Cervicovaginal peroxidases: sex hormone control and potential clinical uses

Thirty-one normal women were studied daily in 41 cycles. Venous blood samples were taken for measurements of luteinizing hormone (LH), estradiol (E2), and progesterone (P), and vaginal examinations were done to obtain cervical mucus and vaginal fluid. The specific activity of guaiacol peroxidase (GP), extracted from cervicovaginal secretions with 0.5 M CaCl2, was determined in the vaginal samples. In the follicular phase, from day -7 to day 0 (the LH +1 day, when ovulation presumably occurred), there was a strong negative correlation between GP and the rising E2 (r = -0.94). On days 1 to 10 after ovulation, there was a strong positive correlation between GP and P (r = 0.84). In nine ovulatory cycles in which P levels did not exceed 8 ng/ml on any day, indicating possible luteal phase inadequacy, there were significantly lower GP levels than in another 32 ovulatory cycles with higher P (P = 0.04). These results suggest that (1) at midcycle, E2 seems to "down-regulate" the GP specific activity; and (2) in the luteal phase, serum P levels parallel those of GP activity, even in the presence of high luteal E2. GP activity profiles during the menstrual cycle can be used to define the fertile period, may prove useful in diagnosing pregnancy, and may be a simple, convenient test for an inadequate corpus luteum.     

Induction of ovulation with pulsatile subcutaneous administration of human menopausal gonadotropin in anovulatory infertile women

Pulsatile administration of human menopausal gonadotropin (hMG) via the subcutaneous route was evaluated in 15 patients with various ovulatory disorders. Administration of hMG was started at a dose of 4.6875 IU (75 IU/day) or 9.375 IU (150 IU/day) per pulse every 90 minutes. Ovulation was observed in 26 (92.9%) of 28 treatment cycles, and two singleton pregnancies were confirmed. Ovarian hyperstimulation was observed in 1 to 26 ovulatory cycles; however, no other side effects were observed during treatment. A regimen of 75 IU/day resulted in a significant increase (P less than 0.0001) of the total dose and prolongation of the treatment period for induction of ovulation, as compared with that of 150 IU/day. Shortened luteal phases occurred in ovulatory cycles induced by pulsatile subcutaneous treatment. Human chorionic gonadotropin administration given every other day until the midluteal phase significantly prolonged the duration of the luteal phase (P less than 0.05). This treatment in patients with the polycystic ovary syndrome was followed by a normalization of luteinizing hormone/follicle-stimulating hormone ratio and resulted in a successful induction of ovulation in 8 to 10 cycles. The present data demonstrated that pulsatile subcutaneous administration of hMG was effective in inducing follicular maturation and ovulation in patients with various types of anovulatory infertility.     

Luteal rescue in in vitro fertilization-embryo transfer

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.     

Differences in hormonal patterns during the first postabortion menstrual cycle after two techniques of termination of pregnancy

Fifteen patients underwent first-trimester abortion by one of two techniques. In group P, seven patients received prostaglandin vaginal suppositories during the 12 hours prior to vacuum aspiration, whereas eight patients in group V were aborted by aspiration alone. During the first postabortion menstrual cycle, daily peripheral blood levels of several hormones, including follicle-stimulating hormone (FSH), luteinizing hormone, human chorionic gonadotropin, estradiol, and progesterone, were determined. Patients in group P demonstrated a more rapid fall in progesterone levels following pregnancy termination (P less than 0.01). They also experienced a more physiologic first postabortion cycle as evidenced by a larger preovulatory estradiol peak (P less than 0.05) and a more normal luteal phase as judged by both the duration and elevation of progesterone levels. Certain endocrine changes common to both groups but different from those of normally menstruating women were also observed. These consisted of short-term spurts of progesterone secretion in many patients (10 of 15) prior to ovulation and exaggerated levels of FSH during the early follicular phase.     

Prolactin levels and bromocriptine treatment of short luteal phase.

Moderate hyperprolactinemia was found in 14 of 30 infertile patients with short luteal phase indicating a possible hypothalamic disorder in these patients. While the cycle length was normal, 28 days, late ovulation around day 18 of the cycle was characteristic of these patients. During bromocriptine treatment, 2.5 mg twice daily, ovulation took place earlier and luteal phase became longer irrespective of the basal serum prolactin level. The mean (+/- SEM) duration of luteal phase was 9.9 +/- 0.2 days in control cycles, and 11.7 +/- 0.5 and 12.2 +/- 0.3 days in two successive bromocriptine cycles (P less than 0.001). In patients taking bromocriptine, luteal phase became longer than 11 days in 37 of 60 treatment cycles, but no significant difference was recorded in the circulating progesterone and LH levels during mid- and late luteal phase. Three patients became pregnant and they all had normal baseline serum prolactin concentrations. Our results show that bromocriptine may be effective even when no apparent indication for prolactin suppression can be demonstrated.     

Luteal phase serum progesterone levels after follicle aspiration with and without clomiphene citrate treatment

Peripheral serum progesterone (P) levels were studied on random days after the spontaneous luteinizing hormone (LH) surge in women who underwent follicle aspiration. Comparisons were made with ovulatory women treated with clomiphene citrate (CC) undergoing follicle aspiration and women undergoing midcycle general anesthesia and laparoscopy without follicle aspiration. There were no differences in mean P levels in the group of women who underwent follicle aspiration, compared with the group who did not. Women treated with CC showed higher P levels during the first week of the luteal phase. During the second week of the luteal phase P levels were similar, regardless of follicle aspiration alone or in combination with CC use. In the groups not using CC, more individual women had P levels less than 10 ng/ml. Follicle aspiration does not appear to reduce luteal phase P levels in groups of patients in the natural menstrual cycle or receiving CC. Some individual patients, however, appear to be at risk for lower P levels, particularly after follicle aspiration or general anesthesia, in the natural cycle.     

Incidence of the luteinized unruptured follicle syndrome in fertile women and in women with endometriosis

One-hundred normal fertile women with normal luteal phase and 118 women with endometriosis underwent luteal phase laparoscopy before day 22. The luteal phase was ascertained by the presence of secretory endometrium and serum progesterone levels higher than 3 ng/ml. The ovaries were carefully inspected for the presence or absence of an ovulation ostium. The percentage of ostii that was observed in fertile women (91%) was similar to that observed in women with mild endometriosis (85%). However, in women with moderate and severe endometriosis, significantly less ostii were noted, respectively 72 and 51%. It is therefore argued that the absence of an ovulation ostium (so-called luteinized unrupted follicle syndrome, LUF) is more frequent in women with moderate and severe endometriosis and may contribute to infertility in this group of women.     

血清抑制素含量在月经周期中的变化及其与卵泡刺激素的相关性

目的了解育龄妇女在月经周期中血清抑制素(INH)含量的变化规律及其与卵泡刺激素(FSH)、黄 体生成素(LH)、雌二醇(E2)及孕酮(P)的相关性。方法建立一种改良的INH放射免疫测定法(RIA),对育龄妇 女正常月经周期中及绝经后妇女血清INH含量的变化进行监测;同时测定血清FSH、LH、E     

Ovulation induction with subcutaneous pulsatile gonadotropin-releasing hormone: the role of supplemental human chorionic gonadotropin in the luteal phase

Four subjects with hypothalamic amenorrhea were administered subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction. GnRH was discontinued at the time of presumed ovulation in all cases. In the first two patients the luteal phase was supported with human chorionic gonadotropin in the initial cycle but not in the second cycle. In patient 3, the reverse was true. Patient 4 had only one cycle on GnRH, and it was unsupported. Daily blood samples were obtained for luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone (P); and frequent pelvic ultrasound examinations were performed. Presumed ovulation as determined by ultrasound occurred in all seven cycles. The first three patients had short luteal phases with poor P production in the unsupported cycles. However, the fourth patient, who had shown pituitary response in GnRH testing, had a normal luteal phase with good P production without human chorionic gonadotropin support. These data support the notion that subcutaneous pulsatile GnRH can be used for the induction of ovulation. However, if the luteal phase is not supported, an inadequate corpus luteum may result.     

Luteotropic effects of tamoxifen in infertile women

Tamoxifen at a dose of 10 mg/day for 5 days was given to five infertile women in the luteal phase. Daily serum samples were obtained during the luteal phase for radioimmunoassay of progesterone (P), estradiol (E2), follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels. The integrated luteal phase concentrations of serum P and E2 before and after cycles of tamoxifen treatment increased from 87.8 +/- 16.2 ng/ml and 1120 +/- 164.4 pg/ml to 131.6 +/- 18.9 ng/ml and 1461 +/- 205.2 pg/ml, respectively (P less than 0.01 and P less than 0.05). No apparent increase in circulating LH levels was seen in one of the five cases, but this patient's serum P and E2 levels rose nonetheless. This suggests that the significant increase in circulating P and E2 induced by tamoxifen is not consistently associated with an increase in serum LH concentration.     

Possible luteolytic effects of luteinizing hormone-releasing hormone in normal women.

The administration of five subcutaneous 250-microgram doses of lutienizing hormone (LH)-releasing hormone (LHRH) at 4-hour intervals, the first injection being given at 8 A.M. on 1 or 2 consecutive days between days 1 and 9 following the LH surge in normal women, shortened the luteal phase from 1 to 4 days in 16 of 17 treatment cycles. There was a better efficiency of treatment when LHRH was administered on days 6 to 9 after the LH surge as compared with days 1 to 5. In fact, the luteal phase was shortened from 3.3 +/- 0.2 days versus 1.4 +/- 0.2 days (P less than 0.01) and the serum progesterone level was decreased to 44% +/- 6% versus 71% +/- 6% of control levels (P less than 0.01) when the neurohormone was injected late as compared with early in the luteal phase. The present data raise the possibility of a luteolytic effect of LHRH in normal women and indicate the interest of such a near-physiologic approach for the control of luteal function and time of appearance of menses.