menotropins and Hyperprolactinemia

Subfertility is defined as the condition of being less than normally fertile though still capable of effecting fertilization. When these subfertile couples seek assistance for conception, a thorough evaluation of male endocrine function is often overlooked. Spermatogenesis is a complex process where even subtle alterations in this process can lead to subfertility or infertility. Male endocrine abnormalities may suggest a specific diagnosis contributing to subfertility; however, in many patients, the underlying etiology is still unknown. Optimizing underlying endocrine abnormalities may improve spermatogenesis and fertility. This manuscript reviews reproductive endocrine abnormalities and hormone-based treatments.

Topics: Adrenal Hyperplasia, Congenital; Androgen-Insensitivity Syndrome; Aromatase Inhibitors; Chorionic Gonadotropin; Clomiphene; Follicle Stimulating Hormone, Human; Humans; Hyperprolactinemia; Hypogonadism; Infertility, Male; Male; Menotropins; Obesity; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Tamoxifen; Thyroid Diseases

With the use of pelvic ultrasound imaging we have found that more than half of the women presenting to our clinic with ovulatory disturbances have polycystic ovaries. As a group hirsutism is common, the serum LH, the LH:FSH ratio and serum androgen levels are higher than in other groups of patients with anovulation, but many of the women we studied were non-hirsute and had normal levels of these hormones. The aetiology of PCOS remains obscure and there is probably more than one cause. Disturbance of hypothalamic/pituitary, ovarian or adrenal function could all result in the development of polycystic ovaries. Our own data, based on pelvic ultrasound and measurement of serum androgen levels, suggest that an ovarian abnormality, other than the obvious morphological one, may be identified in most women although this does not prove (except perhaps in those women with unilateral PCOS) that the ovary is the primary site of the disturbance. Management of ovulatory disturbances includes symptomatic treatment of dysfunctional uterine bleeding and induction of ovulation. Although the ovulation rate following clomiphene is quoted as about 75%, this is probably an overestimate; less than half the 'ovulators' become pregnant and in those who do there is a high risk of early pregnancy loss. Induction of ovulation in clomiphene non-responders remains a difficult problem. The results of ovarian wedge resection are variable and any beneficial effect is short-lived with the risk of long-term infertility due to pelvic adhesions. Laparoscopic electrocautery may be a useful alternative, but it is too early to assess this form of treatment. Of the medical methods of ovulation induction in clomiphene non-responders, two methods have emerged as being highly promising: the first is administration of HMG following suppression of the pituitary by an LH-RH analogue; so far only a very small number of patients have been treated. The second is low-dose FSH. Initial studies, including our own, have shown a high incidence of ovulation and a pregnancy rate of 50%.

Topics: Androgens; Anovulation; Bromocriptine; Chorionic Gonadotropin; Clomiphene; Diagnosis, Differential; Estrogens; Female; Follicle Stimulating Hormone; Glucocorticoids; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Hirsutism; Humans; Hyperprolactinemia; Infertility, Female; Menotropins; Menstruation Disturbances; Obesity; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Ultrasonography

To investigate the effect of induced endogenous hyperprolactinemia on the luteinization process, as expressed by the shift in the P:E2 ratio after hCG injection in IVF cycles.. Serum PRL, E2, and P levels were measured in 49 IVF patients (leuprolide acetate and hMG protocol) on the day of hCG injection. Estradiol and P also were measured on the day after hCG. Serum P:E2 ratios were calculated for two groups of patients; group I (control): PRL < or = 20 ng/mL (conversion factor to SI unit, 1.00); group II (hyperprolactinemia): PRL > 20 ng/mL. Estradiol and P also were measured in follicular fluid (FF) and the gamete performance was compared between groups.. Data analysis showed no significant differences in the mean +/- SD serum peak E2 (pg/mL; conversion factor to SI unit, 3.671) between groups: group I, 1,769 +/- 843; group II, 2,333 +/- 1,194; the mean FF E2 (pg/mL) group I, 351 +/- 221; group II, 370 +/- 186; or the mean FF P (ng/mL; conversion factor to SI unit, 3.180) group I, 8,357 +/- 3,127; group II, 11,354 +/- 12,888. No significant differences were found between groups in the P:E2 ratios on days 1 or 2: group I, 78 +/- 48 and 209 +/- 137; group II, 70 +/- 47 and 224 +/- 197, respectively. The magnitude of the P shift also showed no significant difference between the two groups; the mean +/- SD shift in the P level was 2.9 +/- 2.2 for group I, and 4.3 +/- 5.1 for group II. The serum PRL level had no effect on the fertilization rate (60% for group I and 70% for group II) or on the pregnancy rate (17% for group I and 23% for group II).. These findings suggest that mild endogenous hyperprolactinemia induced by ovarian stimulation does not affect granulosa cell luteinization and gamete performance in humans.

Topics: Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Humans; Hyperprolactinemia; Leuprolide; Menotropins; Ovulation Induction; Pregnancy; Progesterone

To study effect of drug treatment in polycystic ovary syndrome patients with hyperprolactinemia.. We retrospectively studied 63 women with polycystic ovary syndrome and hyperprolactinemia from the Reproductive Medicine Center, Provincial Hospital between January 2005 and March 2007. According to the beginning time of bromocriptine, all women were divided into two groups. Group I was composed of 48 cases who received bromocriptine administration before induction of ovulation cycles, and the dose of bromocriptine was modulated depending on the level of serum prolactin. When serum prolactin was controlled at normal levels, we decreased the dosage of bromocriptine step by step (1.25 mg once), and then continued the treatment at maintenance dosage for no less than 3 weeks. After a baseline ultrasonographic examination on day 3, patients were treated with clomiphene citrate at a dosage of 100 mg (2 tablets/day) for 5 days of a normal cycle or progesterone-induced bleeding. On day 9, we monitored the growth conditions of follicles routinely with trans-vaginal ultrasound. If there was no dominant follicle, we added human menopausal hormone (hMG, 75 U/d) to the protocol. Human chorionic gonadotropin (hCG, 6000-10,000 IU) was given intramuscularly when the mean diameter of a follicle reached at least 18 mm. At the same time we instructed the patients to have sexual intercourses or carried out artificial inseminations before and after ovulation. Group II were 15 cases in which induction of ovulations were commenced almost simultaneously with beginning of bromocriptine. The same protocol was given to patients in group II. The procedures of ovulation induction and the outcomes of treatment were analyzed and compared.. Compared with group II , the days of using hMG in Group I was shorter by instructing the time of sexual intercourse. The difference was significant (P = 0.004). And there were similar results in the artificial insemination cycles (P = 0.009). The rate of pregnancy in group I (40%, 19/48) was higher than that in group II (27%, 4/15), but the difference was not obvious (P = 0.525 ).. Bromocriptine administration before the stimulated ovulation therapy can decrease the total dosage and treatment course of ovulating drugs. Induction of ovulations simultaneously with start of bromocriptine therapy can shorten the treatment time of infertility.

Topics: Adult; Bromocriptine; Chorionic Gonadotropin; Clomiphene; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Prolactin; Retrospective Studies; Treatment Outcome

We report on two males with prolactinoma in whom hyperprolactinaemia and hypogonadism persisted for several years postoperatively despite the administration of a dopamine agonist or bromocriptine. In these patients, a GnRH test revealed no response in the levels of serum LH or FSH. An hCG stimulation test provoked no response in the serum levels of testosterone. Case 1, who was 28 years old at the first visit, received parenteral testosterone and appreciable virilization of the genitalia was noted within a few months. When he married and desired to father a child, the treatment was switched to hCG/hMG combined therapy and spermatozoa appeared subsequently in the ejaculate, although their numbers were low. His wife conceived and delivered a healthy baby girl. Case 2 was a single young man who presented with hypogonadotrophic hypogonadism and hyperprolactinaemia. He was started on hCG injections three times per week and the maturation of his genitalia was advanced rapidly. Semen analyses showed sperm concentration and motility to be within the normal range. Post-treatment GnRH test revealed no improvement in gonadotrophin responses for LH or FSH. In both cases, the hCG test repeated after the gonadotrophin treatment showed normal basal and stimulated testosterone levels. During the course of gonadotrophin treatment in these cases, serum prolactin levels remained elevated, and it is suggested that, in the two cases, the hypothalamo-pituitary function was disturbed by the tumour or its manipulation and the capacity of the pituitary gland to secrete gonadotrophin was impaired. Under such circumstances with persisting hyperprolactinaemia, hCG and/or hCG/hMG combination treatment can induce normal virilization and advance spermatogenesis sufficiently to achieve fertility.

Topics: Adult; Chorionic Gonadotropin; Gonadotropins; Humans; Hyperprolactinemia; Hypogonadism; Male; Menotropins; Pituitary Neoplasms; Postoperative Complications; Prolactinoma

To elucidate the clinical background of the luteal-phase defect (LPD), 201 LPD cycles were studied in 753 infertile women. One hundred and twenty-one cases (62.2%) of LPD showed transient hyperprolactinemia. In transient hyperprolactinemia, there was a significant inverse correlation between serum prolactin (PRL) 30 min after the 500-micrograms intravenous loading of thyrotropin-releasing hormone TRH (PRL30) and progesterone (P4) in the luteal phase (r = -0.67, p less than 0.005). Mature follicles (diameter greater than 20 mm as determined by ultrasonography) were observed in 74 cases (61.2% of the transient hyperprolactinemia cases). On the contrary, in 25 (12.4%) of the 121 LPD cases who showed the hyper-luteinizing hormone (LH) syndrome (LH/FSH ratio greater than 1), only 9 (36%) had mature follicles. Of the remaining 55 cases who showed neither transient hyperprolactinemia nor the hyper-LH syndrome, 27 cases (49.1%) had mature follicles. Five of these patients indicated a significantly higher LH pulse amplitude despite depressed P4 secretion in the luteal phase. From these results, it was concluded that the most common cause of LPD was transient hyperprolactinemia. The second cause of LPD was suspected to be disturbed follicle development due to the inappropriate ratio of LH/FSH in the hyper-LH syndrome. Another cause was speculated to be the primary failure of a response from the corpus luteum to LH. Treatments based on the conclusions mentioned above resulted in a 48.3% pregnancy success rate.

Topics: Bromocriptine; Chorionic Gonadotropin; Clomiphene; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Hyperprolactinemia; Immunoradiometric Assay; Infertility, Female; Luteal Phase; Luteinizing Hormone; Menotropins; Ovarian Follicle; Pituitary Gland; Progesterone; Prolactin; Thyrotropin-Releasing Hormone

Dopamine agonist Bromocriptin tablet has been used in 102 cases, partly for the inhibition of puerperal lactation, partly for the treatment of infertility accompanied by hyperprolactinaemia. On the basis of the clinical results and the changes of PRL level the drug was found to be very effective in both indications. Side-effects necessitating the discontinuance of treatment were not observed.

Topics: Adult; Anovulation; Bromocriptine; Clomiphene; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Infant, Newborn; Infertility, Female; Lactation; Menotropins; Postpartum Period; Pregnancy

Hyperprolactinemia, a known modulator of reproductive function, occurs commonly in women undergoing ovarian stimulation with human menopausal gonadotropins (hMG). Clomiphene citrate (CC) and gonadotropin releasing hormone analogues (GnRHa), when administered during the luteal phase, attenuate the hyperprolactinemic response to hMG. We asked whether follicular-phase administration of CC and GnRHa, as employed clinically in women undergoing ovarian stimulation for in vitro fertilization or gamete intrafallopian transfer, would alter the incidence and severity of hMG-induced luteal-phase hyperprolactinemia. Seventy-five percent of all patients had at least one luteal prolactin level greater than 25 ng/ml, and 40% had mean luteal-phase prolactin levels greater than 25 ng/ml. The incidence of hyperprolactinemia was similar in pregnant and nonpregnant cycles. The incidence of hyperprolactinemia was similar for both the GnRH agonist-treated group and those given clomiphene citrate. The increase in mean luteal prolactin levels over the follicular-phase baseline level was significantly greater in the CC-treated group (P = 0.03). This was due to the significant suppression of follicular-phase baseline prolactin levels in patients receiving CC. We conclude that neither CC nor GnRHa administration in the follicular phase prevents luteal-phase hyperprolactinemia in women undergoing ovarian stimulation with hMG.

Topics: Clomiphene; Female; Fertilization in Vitro; Follicular Phase; Gamete Intrafallopian Transfer; Humans; Hyperprolactinemia; Incidence; Leuprolide; Luteal Phase; Menotropins; Ovary; Ovulation Induction; Prolactin; Retrospective Studies

Prolactin (PRL) has been shown to have inhibitory effect on follicle-stimulating hormone induced aromatase activity and estrogen biosynthesis in human granulosa cells cultured in vitro. To investigate the validity of the hypothesis that transient hyperprolactinemia during controlled ovarian hyperstimulation might influence follicular steroidogenesis and oocyte maturation, we measured serum PRL, estradiol, and progesterone before aspiration of oocytes in women undergoing ovarian stimulation (n = 108) in in vitro fertilization-embryo transfer. No correlation was detected between PRL and total number oocytes, number mature oocytes, fertilization rate, cleavage rate, and pregnancy rate. Transient elevation of PRL was a common finding in patients (57%) but was not associated with a poor clinical outcome.

Topics: Clomiphene; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Hyperprolactinemia; Menotropins; Menstrual Cycle; Oocytes; Pregnancy; Progesterone; Prolactin; Reproductive Techniques

In order to study the function of the hypothalamic-pituitary-testicular axis in men referring for severe oligospermia, the hormonal pattern of 57 oligospermic men was compared to those of 19 healthy volunteers. Fourteen patients had plasma gonadotrophin levels in the normal range contrasting with low plasma testosterone (T) levels. An hyperprolactinemia was found in 2 of these men who were treated with bromocriptine. A dramatic increase in sperm count was obtained on month 9 to 12 of the therapy and 5 pregnancies were obtained. Two men with hypogonadotrophic hypogonadism and azoospermia were treated with gonadotrophins. Such a treatment induced a desquamation of immature germinal cells in the sperm on month 6 and the maturation et spermatozoa on month 18. By contrast to the latter patients, 8 men had a decrease in plasma T levels without clinical signs of hypoandrogenism. The spermocytogram showed numerous immature germinal cells. On month 7 of a treatment using gonadotrophins, the sperm count rose and 4 pregnancies were obtained after 3 to 12 months of therapy. In 2 patients an isolated FSH deficiency was suspected on the basis of undetectable FSH levels unresponsive to the infusion of GnRH. These patients were treated with hMG. This treatment induced a sharp increase in sperm count on month 6. Forty-three patients had an increase in either LH and/or FSH: 24 men had plasma testosterone and LH levels in the normal ranges, contrasting with an increase in plasma FSH level. In such men, the mean of testosterone level was significantly (p less than 0.001) lower than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bromocriptine; Chorionic Gonadotropin; Estradiol; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hyperprolactinemia; Hypogonadism; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Prolactin; Sperm Count; Tamoxifen; Testosterone

Hyperprolactinemia may develop during ovulation induction with human menopausal gonadotropins and hCG (hMG/hCG). Because elevated serum prolactin (PRL) has several adverse effects on female reproductive function, this event has been implicated as a factor to explain the difference between ovulation and pregnancy rates in hMG/hCG treatment cycles. The incidence and severity of hyperprolactinemia in the luteal phase of hMG/hCG-stimulated cycles was investigated in a large series of patients. We analyzed 240 consecutive, ovulatory hMG/hCG cycles in 96 women from July 1984 to January 1986. All women had failed to conceive with clomiphene citrate, and had normal luteal phase PRL levels during unstimulated cycles. Daily serum total estrogens were determined during hMG administration. Serum progesterone and PRL were determined in the mid-luteal phase (7 days post-hCG administration). In 7.5% of the cycles, luteal phase PRL elevations were greater than 25 ng/mL. Only 2.5% of cycles had levels of PRL greater than 35 ng/mL. Hyperprolactinemia infrequently recurred in different cycles of the same patient (two of 16 patients, 12.5%). Cycles with hyperprolactinemia were found to have significantly higher preovulatory estrogen levels. Serum progesterone levels were not significantly decreased in cycles with elevated PRL. Pregnancy rates in cycles with and without hyperprolactinemia were similar (7.7 versus 11.1%, respectively; P greater than .05). We conclude that the development of luteal phase hyperprolactinemia during ovulation induction with hMG/hCG is an isolated event. High preovulatory estrogen levels may predispose to its development. Because hyperprolactinemia is uncommon and is usually mild, other factors must be responsible for the difference between ovulation and pregnancy rates using hMG/hCG.

Topics: Chorionic Gonadotropin; Estrogens; Female; Humans; Hyperprolactinemia; Luteal Phase; Menotropins; Ovulation Induction; Pregnancy; Progesterone; Prolactin

144 patients were treated by 5 different stimulation protocols in the IVF-program of the University Women's Hospital Rostock (Clomiphene/hCG, Clomiphene/Anthrogon/hCG, Pergonal/hCG, Anthrogon/hCG, Folistiman/hCG). Estradiol-17 beta and progesterone were determined during the follicular phase of 172 cycles by RIA. The results were compared between the treatment groups by means of Student's t-test or Mann-Whitney's nonparametric test. Additionally, in 37 cycles prolactin was determined. The levels of estradiol-17 beta in all treated groups were higher as compared with spontaneous cycles. Between the groups statistically significant differences were found in start and velocity of E2-rise, in the average level of E2, and in the level of preovulatory peaks. The latent phase of stimulation was significantly longer in patients treated with pergonal than in Anthrogon treated patients. Moreover, in the Anthrogon group the rate of "high responder" was higher. On average, in patients with a very fast growth rate of estradiol-17 beta (greater than 1.9 nmol/l) during the late follicular phase the percentage of less mature oocytes was increased after follicular puncture. The levels of progesterone started to rise in all groups between day-2 and -1 (day 0: day of LH-peak). On day 0, patients with Pergonal and Anthrogon had the significantly highest level. Levels above the 1s-range occurred in 12 patients during the follicular phase. This elevation of progesterone took place in 3 patients without any rise of basal LH-levels. 80.4% of 37 patients investigated were found to have prolactin levels above 500 mE/l during the late follicular phase. This transient hyperprolactinemia correlated with the rise of estradiol levels and continued during the early and mid luteal phase. Hence preventive administration of bromocryptine appears to be advisable in cycles stimulated with gonadotropins.

Topics: Chorionic Gonadotropin; Clomiphene; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Hyperprolactinemia; Infertility, Female; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation Induction; Progesterone; Prolactin

During cycle stimulation for in-vitro fertilisation (IVF) some patients develop hyperprolactinaemia. Since prolactin (PRL), being an aromatase inhibitor, can interfere with follicular fluid steroid metabolism, we examined the influence of high serum PRL levels on the endocrine response and fertilisation rate of oocytes. 33 consecutive patients stimulated by hMG/hCG for IVF were included in this study. Two groups of patients were established: Group 1 consisting of 18 patients with serum PRL levels less than or equal to 25 ng/ml, and group 2 containing 15 patients, who developed PRL levels greater than 25 ng/ml during cycle stimulation. The serum oestradiol (E2), progesterone (P) and PRL levels 3, 2 and 1 day before and at the day of follicle puncture were evaluated. The decrease of E2 levels at the day of oocyte retrieval was significantly steeper in group 1. The P levels 2 days before oocyte retrieval were significantly higher in group 1 indicating the onset of preovulatory luteinization. Luteinization after the hCG injection was more effective in group 1 resulting in significantly higher P levels. Fertilisation and cleavage rates were significantly higher in patients with normal PRL levels. High serum PRL levels therefore might indicate an interference in follicular and oocyte development leading to oocytes of inferior quality.

Topics: Chorionic Gonadotropin; Cleavage Stage, Ovum; Estradiol; Female; Fertilization in Vitro; Humans; Hyperprolactinemia; Menotropins; Menstrual Cycle; Oocytes; Progesterone; Prolactin