Polycystic Ovarian Patients Research Articles

The Prevalence of Polycystic Ovaries in Women With Infertility

Polycystic ovaries (PCO) are highly prevalent in women presenting with hirsutism or recurrent miscarriage but the functional significance of PCO in ovulatory women presenting with infertility remains unclear. We examined the prevalence of PCO, on ultrasonography, among women presenting with infertility. Among 289 couples classified in four main diagnostic categories, PCO were found in 81 (83%) of 98 anovulatory patients, 40 (53%) of 76 patients whose partners had sperm dysfunction, 26 (50%) of 52 patients with tubal disease and in 28 (44%) of 63 patients with unexplained infertility. By comparison, in a control group of 67 parous volunteers, 19 (28%) were found to have PCO. PCO patients with unexplained infertility had higher midfollicular luteinizing hormone and testosterone compared with the group with normal ovaries. The prevalence of PCO was significantly higher in each of the infertility groups than in controls, and a similar tendency (not significant) was observed among women with unexplained infertility. Ovulatory PCO women with infertility had higher testosterone concentrations in comparison with PCO controls. In summary, the prevalence of PCO among ovulatory women with infertility is higher than that in the normal population, suggesting that PCO may, perhaps by virtue of an effect of hyperandrogenaemia, contribute to the causes of subfertility in women with regular menses.

The prevalence of polycystic ovaries in women with infertility.

Polycystic ovaries (PCO) are highly prevalent in women presenting with hirsutism or recurrent miscarriage but the functional significance of PCO in ovulatory women presenting with infertility remains unclear. We examined the prevalence of PCO, on ultrasonography, among women presenting with infertility. Among 289 couples classified in four main diagnostic categories, PCO were found in 81 (83%) of 98 anovulatory patients, 40 (53%) of 76 patients whose partners had sperm dysfunction, 26 (50%) of 52 patients with tubal disease and in 28 (44%) of 63 patients with unexplained infertility. By comparison, in a control group of 67 parous volunteers, 19 (28%) were found to have PCO. PCO patients with unexplained infertility had higher midfollicular luteinizing hormone and testosterone compared with the group with normal ovaries. The prevalence of PCO was significantly higher in each of the infertility groups than in controls, and a similar tendency (not significant) was observed among women with unexplained infertility. Ovulatory PCO women with infertility had higher testosterone concentrations in comparison with PCO controls. In summary, the prevalence of PCO among ovulatory women with infertility is higher than that in the normal population, suggesting that PCO may, perhaps by virtue of an effect of hyperandrogenaemia, contribute to the causes of subfertility in women with regular menses.

Follow-up of 32 hypothalamo-hypopituitary patients treated with pulsatile gonado tropin-releasing hormone or human menopausal gonadotropin

In a clinical retrospective study, a follow-up of hypothalamo-amenorrheic patients treated firstly with gonadotropin-releasing hormone (GnRH) pump stimulation and secondly with human menopausal gonadotropin (hMG) was performed. Thirty-two hypothalamo-amenorrheic patients, 24-38 years old, were submitted to 103 GnRH stimulation cycles. Seven, with polycystic ovaries (PCO) on ultrasound, were stimulated with hMG after one or several unsuccessful pump cycles.Ovulation was confirmed by a luteinizing hormone (LH) surge or triggered by human chorionic gonadotropin in 80 out of 103 cycles (77.7%/cycle) leading to 62 timed sexual intercourses and 17 intrauterine inseminations (IUI). Twenty-one pregnancies (26.3%/cycle) terminated in eight abortions (38.1%/pregnancy) and 13 deliveries (40.6%/patient). hMG stimulation, in the seven PCO patients (six IVF, one IUI), led to four additional deliveries in three patients. Five patients became pregnant spontaneously after pump failure (n = 2) or unsuccessful IVF (n = 3). Combining all cycles, 17 deliveries were obtained in 16 patients. No case of ovarian hyperstimulation syndrome (OHSS) was observed.GnRH is an efficient and safe treatment of hypothalamo-amenorrheic-induced anovulation. Following GnRH or hMG ovarian stimulation, spontaneous ovulation and conception may be restored in certain hypothalamo-amenorrheic patients.

Oocyte quality in polycystic ovaries revisited: identification of a particular subgroup of women.

Our purpose was to assess the endocrine status of women with polycystic ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine markers of the syndrome, in an attempt to define a subpopulation with poor quality oocytes. This was a retrospective study. Patients were first endocrinologically analyzed: serum levels of androgens (T, androstenedione, DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose tolerance test (OGTT) were recorded and are expressed as absolute values and area under the curve (AUC). Subsequently, they were followed over a 2-year period in which patients underwent several attempts of IVF as well as serving as oocyte donors. Patients were divided into three groups: group I (n = 4) was women who displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles in which they served as donors; group II (n = 16) was PCO patients in whom IVF (n = 38) and/or oocyte donation cycles (n = 42) resulted in pregnancies; and group III (n = 13) was IVF patients with normal appearance of the ovaries by ultrasound. The endocrine status was compared with the IVF results. There was no difference among groups in the endocrinological parameters tested, except for the OGTT which identified women in group I as having higher serum glucose and insulin levels than patients in groups II and III. Similarly, the OGTT showed higher serum glucose values in group II compared to group III. Women in group I were also obese. Patients in group III were older than PCO patients and needed more gonadotropins to reach an ovarian response which resulted in a reduced number of oocytes retrieved. Fertilization was also impaired in group I, in which no pregnancy was recorded. This study shows that there is a particular subgroup of PCO patients with lower fertilization rates and embryos unable to implant. These patients are obese and nonhyperandrogenic and show derangements of insulin secretion.

Treatment of Anovulation With Pulsatile Gonadotropin-Releasing Hormone

Filicori, M.; Flamigni, C.; Dellai, P.; Cognigni, G.; Michelacci, L.; Arnone, R.; Sambataro, M.; Falbo, A. Author Information

Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles.

Pulsatile GnRH (pGnRH) was administered to 292 anovulatory patients in 600 consecutive cycles between February 1984 and February 1993. This represents the largest single pGnRH series ever reported. Patients were divided into the following groups: primary hypogonadotropic amenorrhea (PHA), 73 patients, 161 cycles; other hypogonadotropic hypogonadisms (OHH), 57 patients 107 cycles; multifollicular ovary (MFO), 39 patients 75 cycles; polycystic ovary (PCO), 85 patients 172 cycles; and other hyperandrogenic anovulations (OHA), 38 patients 85 cycles. GnRH was administered iv at a dose of 1.25-20.0 micrograms every 30-120 min; most cycles (505) were performed with a regimen of 2.5-5.0 micrograms GnRH every 60-90 min. In 228 cycles of MFO, PCO, and OHA patients, pGnRH was preceded by GnRH agonist (GnRH-A) suppression. Ovulatory rates were 75%, and pregnancy occurred in 105 cycles (pregnancy rate of 18%/treatment cycle and 23%/ovulatory cycle). Ovulatory and pregnancy rates were higher in PHA, OHH, and MFO and lower in PCO and OHA. Only 4 multiple pregnancies occurred (3.8%), none after GnRH-A suppression. The abortion rate was 30% and was highest in PCO (45%). GnRH-A pretreatment improved ovulatory rates only in PCO (from 49% to 71%; P < 0.001), whereas it had no significant effect on pregnancy and abortion rates in any group. Higher weight and insulin were associated with lower ovulatory and pregnancy rates; higher LH and testosterone were associated with lower ovulatory rates only. We conclude that 1) pGnRH is a highly effective ovulation induction method; 2) pGnRH does not cause ovarian hyperstimulation; 3) low dose pGnRH is associated with a remarkably low incidence of multiple pregnancy; 4) GnRH-A pretreatment improves pGnRH outcome in PCO and further lowers the incidence of multiple pregnancy; 5) pGnRH is associated with relatively elevated abortion rates, particularly in PCO; and 6) pGnRH is less successful in overweight patients and when high baseline LH, testosterone, and insulin levels are present.

Native gonadotropin-releasing hormone for triggering follicular maturation in polycystic ovary syndrome patients undergoing human menopausal gonadotropin ovulation induction

To evaluate the role of GnRH administration instead of hCG for triggering follicular maturation in patients with polycystic ovaries (PCO) undergoing hMG ovulation induction when the late follicular 17-beta-E2 levels are > 1,600 pg/mL (> 6,000 pmol/L). Prospective study. Infertility outpatient clinic of Rambam Medical Center (general hospital), Haifa, Israel. High serum E2 concentrations from 1,600 to > 3,600 pg/mL (2,800 +/- 68, mean +/- SD [6,000 to > 13,000 pmol/L, 10,279 +/- 2,500]) were experienced in 44 hMG cycles. The number of preovulatory follicles visualized by transvaginal sonography was between 8 and 25. An IV injection of 200 micrograms GnRH was administered for triggering final follicular maturation and ovulation, instead of 10,000 IU IM hCG, usually injected for this purpose, when the E2 levels are < or = 1,600 pg/mL (6,000 pmol/L). Serum E2 and P levels were monitored in the luteal phase. In cycles where E2 decreased to < or = 1,360 pg/mL (5,000 pmol/L), 2,500 IU hCG was administered once or twice at 3-day intervals for luteal support. Pregnancy and abortion rates and the rate of ovarian hyperstimulation syndrome (OHSS). Ten pregnancies were generated by the hMG and GnRH co-treatment in 32 patients (31.2%), in 44 cycles (23%). Two pregnancies aborted (20%), and eight generated eight healthy neonates. Ovarian hyperstimulation syndrome occurred in two cycles of patients who were both pregnant. All but two of these PCO patients also have undergone 69 hMG and hCG cycles. Only 7 patients conceived (23%) 10 times (10/69, 14.5%); 5 of these pregnancies (50%) were multiple gestations (3 twins, 1 sextuplet, and 1 heptuplet gestation). The pregnancy wastage rate was 30% (3/10). The use of native GnRH to trigger ovulation in PCO patients with late follicular E2 levels > 1,600 pg/mL (6,000 pmol/L) appears to be comparable with prior hMG and hCG cycles in terms of pregnancy rate, pregnancy wastage, risk of multiple gestation, and incidence of severe ovarian hyperstimulation. Unlike hMG and GnRH-agonist, which is associated with luteal phase dysfunction, hMG and GnRH offers a preferable alternative due to the ability of hCG luteal support and rescue, providing the E2 levels are not dangerously increased.

Increased insulin secretion in patients with multifollicular and polycystic ovaries and its impact on ovulation induction

To assess the oral glucose tolerance test (OGTT)-stimulated insulin secretion and its relation to pulsatile GnRH ovulation induction outcome in patients with multifollicular or polycystic ovaries (PCOs). Prospective study. Reproductive Endocrinology Center, University of Bologna, Bologna, Italy. Eight normal and 29 anovulatory women (8 with multifollicular ovaries and 21 with PCOs). A standard OGTT was performed in all subjects. In all anovulatory patients, ovulation was induced with pulsatile GnRH (5 micrograms i.v. every 60 minutes). In multifollicular ovary patients, pulsatile GnRH was administered alone, whereas in PCOs it was preceded by GnRH agonist (GnRH-a) suppression. Glucose, insulin, and C-peptide response to the OGTT, expressed as area under the curve (AUC). Ovulatory rates in response to pulsatile GnRH. Insulin and C-peptide AUC were greater than controls in both multifollicular ovary and PCO patients. Insulin AUC was positively correlated to ovarian volume. Ovulation was achieved in 88% and 57% of multifollicular ovary and PCO patients, respectively. Body mass index and glucose AUC but not insulin and C-peptide AUC were significantly greater in the anovulatory PCO. [1] Insulin AUC was increased in both multifollicular ovary and PCO patients; [2] derangements of insulin secretion may be present in a greater variety of anovulatory patients than previously thought; [3] insulin levels during the OGTT did not predict a response to pulsatile GnRH in PCOs, suggesting complex insulin interactions at the ovarian level; [4] given the in vitro stimulatory properties of insulin on granulosa cells synergistic with FSH, we propose that excessive insulin levels may contribute to the ovarian enlargement often found in multifollicular ovary and PCO patients.

In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients

To determine the maturational and developmental competence of immature oocytes recovered in situ from anovulatory and ovulatory patients with polycystic ovaries (PCO). A newly designed method for recovery of immature oocytes from 2 to 10 mm follicles by transvaginal ultrasound or laparoscopy was used to compare the recovery and maturation of oocytes from 9 anovulatory polycystic ovarian syndrome (PCOS) patients and 10 ovulatory patients without polycystic ovaries (PCO) (experiment 1). In a second study (experiment 2), we compared the maturation, fertilization, and development of oocytes recovered from another 10 anovulatory PCOS and 13 ovulatory PCO patients. Two types of culture methods and time intervals for maturation were also examined. In experiment 1, a significantly higher number of immature oocytes were recovered from PCOS patients (15.3) compared with non-PCO patients (2.8). Sixty-five percent of oocytes cultured in medium with gonadotropins, estrogen, and fetal calf serum matured to metaphase II by 43 to 47 hours, and 81% were mature at 48 to 54 hours of culture. Thirty-four percent of the inseminated oocytes fertilized and 56% of the cultured pronuclear oocytes cleaved to eight cells or more. In experiment 2, there was no significant difference between anovulatory PCOS and ovulatory PCO patients in the number of oocytes recovered or their maturation, fertilization, and development. There was no difference between oocytes matured in medium or in coculture with mature granulosa cells, with or without added hCG. However, significantly fewer oocytes were immature and more fertilized when oocytes were inseminated after 34.5 to 35.5 hours of maturation than 29.5 to 32.5 hours of maturation. A pregnancy and the birth of a normal baby occurred in one of the anovulatory PCOS patient receiving an abbreviated steroid replacement protocol after ET. Immature oocyte recovery could be developed as a new method for the treatment of women with infertility due to PCO because the oocytes of these patients retain their maturational and developmental competence.

Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries.

Raised insulin levels are now recognized as a characteristic feature of women with polycystic ovaries (PCO), and hyperinsulinism has been shown to stimulate androgen production in such women. We have, however, recently shown that hyperinsulinaemia is present only in the obese subjects with PCO in whom insulin concentrations correlate with those of luteinizing hormone. We therefore studied 24-hour blood profiles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in obese and non-obese women with PCO, for comparison with their levels of insulin, C-peptide and other hormones, such as androgens which are known to be disturbed in PCO. Mean 24-hour GH levels were higher overall in PCO than in control subjects, although the difference was not significant. When, however, a separate analysis was made in obese as compared with non-obese PCO patients, GH concentrations were significantly higher in the non-obese group than in the obese (p = 0.0005). There was a significant negative correlation between body mass index and mean 24-hour GH concentrations (r = -0.641; p = 0.0006). IGF-I concentrations were however similar in the PCO group overall and in controls, as well as in the obese and non-obese PCO patients. The 24-hour blood glucose profile pattern was significantly different in PCO women from controls (p = 0.009), with absence of post-prandial peaks in blood glucose concentrations. These changes were most marked in the non-obese PCO group, who also had significantly lower blood glucose levels than either controls or obese PCO subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Transvaginal ultrasound-guided follicular aspiration in the management of anovulatory infertility associated with polycystic ovaries

To investigate whether or not transvaginal ultrasound (US)-guided follicular aspiration can effectively induce ovulation and facilitate pregnancy in anovulatory patients with polycystic ovaries (PCO). Eight patients with polycystic ovarian disease (PCOD) and 10 patients with PCO were participants who failed to ovulate by the medical therapies. Most of persistent follicles were punctured, and their contents were thoroughly aspirated during the midluteal phase. The same ovarian stimulation regimen as used in the previous cycles were administered in the cycles after the aspiration. Evidence of ovulation and a subsequent pregnancy was ultrasonically monitored after the aspiration, and the responsiveness of pituitary gonadotropins to gonadotropin-releasing hormone was tested in these patients. The ovulation rates were 87.5% per patient, 52.6% per cycle monitored in PCOD patients and 100% per patient, 63.3% per cycle monitored in PCO patients, respectively. Half of the patients both with PCOD and PCO achieved pregnancy after the aspiration. A significant decrease (P less than 0.05) of the basal and peak levels of serum luteinizing hormone was observed after the aspiration. The US-guided follicular aspiration seems to be a new surgical method for treating anovulatory patients with PCO.

Plasma androgens and oestradiol during oral glucose tolerance test in patients with polycystic ovaries

Hyperinsulinaemia is common patients with polycystic ovaries (PCO), and a relationship between hyperinsulinaemia and hyperandrogenaemia has been suggested. We studied the effect of increased circulating insulin in response to an oral glucose tolerance test (OGTT) on plasma levels of androgens and oestradiol in PCO patients and in healthy control subjects. A 75 g, 3 h oral glucose tolerance test (OGTT) was performed in eight non-obese and seven obese PCO patients, and in 10 non-obese control subjects. An additional group of five women were fasting during the study period. The increase in insulin concentration was higher in obese and non-obese PCO patients than in non-obese control subjects, and the peak values were observed at 30 or 60 min. In the fasting control subjects, the mean concentration of androstenedione decreased slightly due to a diurnal variation. During the OGTT, mean concentrations of androstenedione decreased in all groups at 30 min, after which a slight increase was observed in PCO patients and a plateau in control subjects. Similarly, mean testosterone increased after an initial decrease in obese PCO patients whereas no change was found in non-obese PCO patients. No statistically significant differences were found in the responses of androstenedione or testosterone levels to OGTT in obese or non-obese PCO patients compared to normals. No significant responses of plasma oestradiol levels to OGTT were found. These findings failed to demonstrate any significantly abnormal acute androgen responses to OGTT-stimulated hyperinsulinaemia in PCO patients, but did not exclude possible long-term effects of hyperinsulinaemia.

HLA ASSOCIATIONS IN PATIENTS WITH POLYCYSTIC OVARIES AND IN PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA CAUSED BY 21‐HYDROXYLASE DEFICIENCY

Ninety-nine Caucasian patients with ultrasonically detected polycystic ovaries (PCO) were typed for human leucocyte (HLA) antigens. Fifty patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency were similarly typed. Among the patients with PCO, there was a significant increase in the frequency of HLA DRW6 (P = 0.0027) compared with that found in a control population, which remained significant (P = 0.027) when corrected for the number of antigens tested. This difference was reduced, but remained significant (P = 0.006), when the patients with CAH and PCO were added. There was also a significant decrease in the frequency of HLA DR7 (P = 0.017) among the patients with PCO compared with a control population, but there was no distortion of the frequencies of HLA A, B or Cw antigens. Among the patients with CAH, previously well documented associations of HLA B14 and DR1 with non-classical disease were confirmed. The frequency of HLA Bw47 was increased among the whole group of CAH patients (P = 0.05) but was not increased among those with classical salt-wasting (SW) or simple virilizing (SV) disease. Family studies were performed in close female relatives of 16 of the PCO patients and 21 of the CAH patients but no evidence for genetic linkage between HLA and PCO status could be found. These data suggest that there is no significant component of disturbed adrenal steroid 21-hydroxylase activity to account for the PCO morphology, although there may be some other genetic factor, more proximal to the centromere on chromosome 6, affecting the development of polycystic ovaries.

Paradoxical Growth Hormone Response following Thyroid-Stimulating Hormone Administration in the Polycystic Ovary Syndrome

Growth hormone (GH) and prolactin (PRL) responses after TRH administration were studied in 31 women presenting with the clinical, biochemical and ultrasonographic characteristics of the polycystic ovarian (PCO) syndrome; their results were compared with those of 20 normally menstruating women investigated during the early follicular phase of the cycle. Based on the GH responses two PCO subgroups were observed: (a) nonresponders (n = 16) who showed delta max GH responses (0.7 +/- 0.27 ng/ml, x +/- SE) similar to those of the normals (0.97 +/- 0.20 ng/ml), and (b) responders (n = 15), 48.4% of the PCO patients who showed a paradoxical increase in GH levels (delta max GH, 18.0 +/- 1.96 ng/ml) following thyrotropin-releasing hormone (TRH) administration significantly higher than those observed either in nonresponder PCO patients or in normals. Furthermore, basal GH levels were found to be significantly higher in the responder PCO subgroup (5.65 +/- 0.75 ng/ml) compared to either nonresponders (1.58 +/- 0.21 ng/ml) or normals (1.8 +/- 0.18 ng/ml). However, no correlation was found between basal GH levels and delta max GH responses observed. Additionally, basal PRL and delta max PRL levels following TRH administration did not differ either between the two PCO subgroups or those observed in normal controls. delta 4A, T and E2 levels were similar between the two PCO subgroups. No correlation was found between the delta max GH responses to delta max PRL or the post-luteinizing hormone-releasing hormone stimulation test delta max luteinizing hormone:follicle-stimulating hormone ratio observed or to steroid levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of combined exogenous gonadotropins and pulsatile gonadotropin-releasing hormone in patients with polycystic ovarian disease: a new approach to induction of ovulation.

A combined regimen based on exogenous gonadotropins followed by pulsatile gonadotropin-releasing hormone was attempted in order to induce ovulation in a group of patients with polycystic ovarian disease. The women were selected on the basis of previous unsuccessful treatment with clomiphene citrate, gonadotropin and pulsatile gonadotropin-releasing hormone used separately. At our first attempt at application of this new approach, in all patients follicular growth was recorded and ovulation was induced with exogenous chorionic gonadotropin, without hyperstimulation. Two clinical pregnancies were established. Retrospective hormonal evaluation showed the presence of two premature luteinizations. Pulsatile gonadotropin-releasing hormone administration following follicular recruitment with exogenous gonadotropin may therefore be considered an effective therapy for polycystic ovarian patients resistant to conventional treatment.

Free α-subunit response to gonadotropin-releasing hormone in women with polycystic ovaries

The response of glycoprotein hormone free alpha-subunit to gonadotropin-releasing hormone (GnRH) was evaluated in 12 women with polycystic ovaries (PCOs). Six of these women were premedicated for 3 days with micronized 17 beta-estradiol before receiving a 100-micrograms bolus of GnRH. In nonmedicated PCO patients, GnRH did not significantly alter basal free alpha-subunit levels. In four of the six PCO patients receiving estrogen premedication, a significant increase in free alpha-subunit was observed; these four patients had low progesterone levels at the time of the GnRH test. Among the six premedicated patients, two had elevated (greater than 4 ng/ml) progesterone levels, and the GnRH tests showed no significant effect on the levels of free alpha-subunit. The study revealed a dissociation between the free alpha-subunit responses to GnRH and the responses of luteinizing hormone; a closer relationship was observed between free alpha-subunit and follicle-stimulating hormone responses. It was concluded that the lack of a free alpha-subunit response to GnRH in PCO patients is not due to a primary inability of the pituitary gonadotroph to produce free alpha-subunit but is a consequence of an altered estrogenic milieu, and a free alpha-subunit response to GnRH may reflect the replenishment of both follicle-stimulating hormone and luteinizing hormone in the gonadotrope.

Multifollicular Ovaries

ADAMS, J.; POLSON, D. W.; ABDULWAHID, N.; MORRIS, D. V.; FRANKS, S.; MASON, H. D.; TUCKER, M.; PRICE, J.; JACOBS, H. S. Author Information

Effects of luteinizing hormone and dibutyryl adenosine 3',5'-monophosphate in cultured granulosa cells from polycystic ovaries.

The present study was undertaken to assess the ability of granulosa cells from subjects with normal and polycystic ovaries (PCO) to secrete progesterone throughout a 10-day culture period. LH levels in serum and follicular fluid from PCO patients were significantly (P less than 0.001) higher than those in normal subjects. In the absence of LH, progesterone secretion by granulosa cells cultured from PCO follicles did not differ significantly from that of cells from normal early and midfollicular phase follicles. Granulosa cells cultured from follicles from normal subjects in the early and midfollicular phases responded to LH (100 ng/ml) with an 8- to 20-fold increase in progesterone production. In contrast, LH increased progesterone production to a much lesser extent (up to 4-fold) in cells from the ovaries of patients with PCO. Progesterone secretion by granulosa cells from normal ovaries in response to LH diminished as intrafollicular endogenous progesterone and LH levels increased. Cells from PCO follicles cultured with (Bu)2cAMP (100 micrograms/ml) secreted progesterone in quantities comparable to those secreted by (Bu)2cAMP-stimulated normal ovaries in the early and midfollicular phases. These data demonstrate the discrepancy between the ability of granulosa cells from PCO and normal follicles to secrete progesterone in response to stimulation by LH and (Bu)2cAMP. These results suggest that in women with PCO, the persistent elevation of follicular LH may lead to impaired progesterone production in response to exogenous LH.

Ovarian membrane receptors for LH, FSH and prolactin during the menstrual cycle and in polycystic ovary syndrome.

To investigate the role of ovarian membrane receptors for LH, FSH and prolactin of patients with developing polycystic ovary (PCO) syndrome, seven patients were selected and the receptor function was studied in relation to changes of several serum hormone levels. The results were compared with those from individuals with regular menstrual cycles in the late follicular (LF; n = 6) and midluteal (ML; n = 6) phases. LH receptor binding in the normal cycle remained low (1.73 +/- 0.14 fmole/mg homogenate protein) in the LF phase and elevated 3 fold in the ML phase. LH receptors in the PCO patients maintained a higher binding level than that in the LF phase, being close to the ML level. FSH receptors were at a high level in the LF phase (4.09 +/- 0.40 fmole/mg homogenate protein), but decreased by 23% in the ML phase. In the PCO group the ovarian FSH receptor showed a high level, near to that in the LF phase. Prolactin receptors showed no significant changes among the two controls and PCO group. PCO patients showed increased levels of serum LH and testosterone and a raised ratio of estrone to estradiol, although there was no change in the serum FSH level. These data suggested that the LH receptor binding in PCO was not so low as to the LF level. A lack of the down-regulation mechanism of LH receptors, in spite of the high level of serum LH in PCO, might be one of the clues to elucidate the pathophysiological mechanism in developing PCO syndrome. Elevated levels of the gonadotropin receptors, especially FSH receptors, seem to be involved in the high incidence of ovarian hyperstimulation during hormone treatment.

Enhanced ovarian gonadotropin receptors in the testosterone-induced polycystic ovary in rats.

To establish the role of hormone receptors in patients with polycystic ovary (PCO), PCO rats were prepared by treating with testosterone propionate (TP). Five-day old immature female rats were subcutaneously injected with 1.25 mg TP in sesame oil. They were then killed at the age of 12 weeks. The ovarian receptors for LH and FSH as well as serum hormone levels were investigated in PCO rats and also in control rats at the various stages of the estrous cycle. The LH receptor binding in the TP-treated ovaries was elevated almost as high as that of proestrus control, and was observed to be higher than the other control. The FSH receptor binding of PCO rats was elevated to 173% of that of diestrus control, which showed the highest value throughout the cycle. Thus, the gonadotropin receptors in PCO rats appeared to be in an activated state. High levels of the receptor binding were due to an increase in receptor binding sites. Serum LH level was significantly higher than that of diestrus control but still remained lower than that of proestrus control. In contrast, FSH level was as low as that of diestrus control. Prolactin level was markedly elevated and 17- and 2-fold higher than that of diestrus and proestrus control, respectively. Estradiol level was higher than that of diestrus control, increasing to almost the same level during proestrus control. While progesterone level was largely depressed to 23 and 13% of that of diestrus and proestrus control, respectively, testosterone level was almost the same as that of diestrus control. From these results, it was suggested that tonic secretion of LH, low level of FSH, and markedly high levels of prolactin would increase the gonadotropin receptors and result in extremely low production of progesterone in rat ovaries. Clinically, elevated levels of the LH and FSH receptors may be a relevant occurrence in PCO patients.