Prolactin and placental hormone levels during pregnancy in prolactinomas

Prolactin (PRL) and the placental hormones, estradiol (E2), estriol (E3), progesterone (PG), chorionic gonadotropin (HCG), and placental lactogen (HPL) were serially measured throughout pregnancy and early postpartum in three patients with prolactinomas in whom pregnancy was achieved by one of the three modalities of treatment: bromocriptine administration (patient I), irradiation of the pituitary (patient II), and human gonadotropin administration after excision of the adenoma (patient III). It was found that PRL in patient I reached the high pretreatment levels in the 2nd month of pregnancy and increased to further abnormal concentrations in the last 2 months, but fell at the onset of labor 1 week after an episode of severe headache. The PRL changes in this patient were attributed successively to tumor expansion and apoplexy. In patient II PRL decreased after irradiation, but was not normalized. During pregnancy it remained moderately increased presenting minor fluctuations. The third patient with postoperative GH and TSH pituitary insufficiency had low pretreatment PRL levels which remained practically unchanged throughout pregnancy. The two last patients gave birth to identical twins. The placental hormones were found normal in all three patients but E2 and PG were relatively increased during the last weeks of pregnancy in the twin pregnancies. Amniotic fluid and umbilical cord PRL and E2 concentrations were normal. The patients presented agalactia and suckling did not induce a PRL increase. We conclude that a) serial PRL measurements during pregnancy reflect the changes occurring in the prolactinomas and are essential in monitoring the patients bearing these tumors; b) maternal hyperprolactinemia or failure of PRL to increase during pregnancy do not influence either the secretion of placental hormones or PRL concentration in amniotic fluid and the newborn; and c) hyperprolactinemia during pregnancy is of maternal pituitary origin.     

Conservative management of suspected prolactin secreting pituitary adenoma during pregnancy

Seventeen women with prolactin levels of 100 ng/ml and above suspected of harboring prolactin-secreting pituitary adenoma, form the basis of this study. Ten patients had radiological signs of an adenoma while in 7 the radiological criteria for such a diagnosis were not fulfilled. Ovulation and pregnancy were induced with bromocriptine in all 17 patients. They were carefully observed during pregnancy and following delivery. All gave birth to full-term babies after uneventful pregnancies, except for one patient who experienced intrauterine fetal death at 31 wk of gestation. It is our policy that women with suspected intrasellar prolactin-secreting pituitary adenoma be allowed to conceive and give birth without previous surgical intervention. The patient should be closely followed during pregnancy for clinical symptoms of enlargement of the tumor, including periodic visual field examinations. In cases of neurologic or ophthalmologic complications, surgery or bromocriptine administration without interruption of pregnancy is advocated, or if lung maturity is achieved, delivery should be induced.     

Induction of ovulation in women with hyperprolactinemic amenorrhea using clomiphene and human chorionic gonadotropin of bromocriptine.

Clomiphene citrate (Clomid), when given alone, is generally considered ineffective in inducing ovulation in women with hyperprolactinemia. This study reports the treatment of 29 infertile women with hyperprolactinemic amenorrhea. Twenty-one patients (eighteen of whom had previously had no ovulation response to Clomid alone) were treated with a combined regimen of Clomid (100 to 200 mg/day for 5 days) and two injections of 5000 IU of human chorionic gonadotropin (HCG), the first 8 to 10 days after Clomid withdrawal and a second injection 1 week later. Basal body temperature charts, conception, and/or plasma progesterone measurements showed that 19 patients ovulated (90%). There were 17 pregnancies in 12 of 21 patients (57% pregnancy rate) with 15 single live births and two abortions. When bromocriptine (Parlodel) became available, a total of 22 patients (including 14 patients previously treated with Clomid/HCG, six of them successfully) with amenorrhea associated with hyperprolactinemia were treated with this drug with dosages varying from 2.5 mg to 15 mg/day. Ovulation was confirmed in 20 patients (90%). There were 17 pregnancies in 15 patients (68% pregnancy rate) with 15 single live births and two first-trimester abortions. In all, 21 of 29 patients (73%) achieved one or more pregnancies resulting in live births with one or both of the above treatments. It is concluded that a combined Clomid/HCG regimen can often be used as an effective alternative to bromocriptine therapy in the treatment of infertility associated with hyperprolactinemic amenorrhea.     

A rational approach to ovulation induction

Appropriate investigation has led to the recognition of five major endocrinologic categories of anovulatory patients. The clinician is able to follow a definitive therapeutic program for each of these; and except where the FSH levels are elevated, pregnancy rates should approach values observed for normally ovulating women. Although clomiphene citrate is likely to remain the most common drug prescribed to anovulatory women, treatment programs with clomiphene have recently been modified with much improved success rates resulting. Bromocriptine, the drug of choice for women with hyperprolactinemia, restores ovulatory cycles in most women treated. It not only restores fertility, however, but also reduces tumor growth in patients with pituitary adenomas, making surgical removal often unnecessary. Exogenous gonadotropin therapy should be reserved for patients who do not respond to treatment with clomiphene and/or bromocriptine. With adequate monitoring, the multiple pregnancy rate should be able to kept below 20% and high-multiple pregnancies avoided. Pulsatile GnRH therapy is likely to replace gonadotropin therapy for most patients, because this therapy has distinct advantages in terms of cost, patient convenience, and a lowering of multiple pregnancy rates.     

Immuntherapie bei habituell abortierenden Paaren

After habitual abortions and the exclusion of nonimmunological causes of miscarriage, 26 patients were treated with lymphocytes of their partners of prophylaxis of abortion. The first treatment was done during early pregnancy in eight patients. Of the remaining 18, 12 have become pregnant up to now. Five pregnancies have gone to term, one is in the 13th week at the moment, and five are in the 20th week. Two patients lost their baby after the 20th week due to nonimmunological causes. Again seven patients had an early spontaneous abortion. Thus, the success rate of the immunological therapy is 63.2% at the moment.     

Outcome of Treatment with Bromocriptine in Patients with Hyperprolactinaemia

Results in 136 hyperprolactinaemic women who presented with infertility, amenorrhoea, menstrual irregularities and/or galactorrhoea are reported. There was radiographic evidence of pituitary microadenoma in 21 (15.4%) patients and 5 (3.7%) had macroadenoma. Four patients were taking antidepressants, 2 antihypertensive drugs and 7 had taken oral contraceptives for a period of 6 months to 5 years. The remaining patients had no obvious cause for elevated prolactin levels. Patients with pituitary adenoma had a significantly higher (p less than 0.001) baseline serum prolactin level (182 +/- 4.6 ng/ml) than those with no adenoma (59.2 +/- 4.2 ng/ml). All patients in the study were treated with bromocriptine (2.5-10 mg) to normalize serum prolactin or to achieve a pregnancy. The patients without an adenoma required a significantly smaller dose of bromocriptine (2.5-5.0 mg) (p less than 0.005) than those with an adenoma. Galactorrhoea disappeared in all 64 patients within 2-4 months of treatment, sixty-six (71%) of the 93 patients who desired pregnancy achieved it within 3 to 8 months of bromocriptine therapy; 32 of these patients received additional treatment with clomiphene and human chorionic gonadotrophins for induction of ovulation. In the remaining 70 patients menstruation became regular and ovulation was evident in 40% of them. There was no significant difference in the pregnancy rate between the patients with or without pituitary adenoma. Similarly, presence of galactorrhoea or a high level of prolactin did not influence the pregnancy rate. No complications were observed during pregnancy related to pituitary adenomas; 8 (12%) pregnancies ended in first trimester abortion. No lethal congenital fetal abnormalities were observed in the patients treated with bromocriptine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk of a second consecutive first-trimester spontaneous abortion in women who conceive with menotropins

It is generally recognized that a spontaneous abortion rate of approximately 25% exists in human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG)-induced pregnancies. Despite this, little is known regarding the prognosis of future menotropin-induced pregnancies in women who abort in their first hMG pregnancy. We retrospectively reviewed the obstetrical outcome of women who achieved two or more menotropin pregnancies between the years 1980 and 1987. Nineteen of 40 patients (48%) whose first hMG pregnancy ended in an early spontaneous abortion went on to abort in a second hMG pregnancy, as compared with only 1 of 15 women (6.7%) whose first hMG pregnancy was successful. Age, parity, weight, height, and plasma estradiol levels at hCG administration did not differ between the two groups. From this data we conclude that women whose first hMG pregnancy results in a spontaneous abortion are at high risk for another spontaneous abortion in a subsequent menotropin conception.     

Management of hyperprolactinemic infertility

Pathological hyperprolactinemia may cause defective ovulation and reduced fecundability. Abnormal prolactin (PRL) secretion is usually related to an idiopathic hypothalamic dysfunction or to the presence of a pituitary adenoma. The use of medication is the most common cause of functional hyperprolactinemia. Pituitary prolactin secreting adenoma is classified according to size: micro (the vast majority) being smaller than 10 mm in diameter or macroprolactinoma (very few) of larger size.An excessive PRL secretion decreases the pulsatile release of GnRH impairing the pituitary production of FSH and LH. Furthermore it may directly impair the endocrine activity of ovarian follicles. As a consequence: defective luteal phase, inconstant ovulation and chronic anovulation are conditions frequently observed in young hyperprolactinemic patients. In addition 5% of unselected, asymptomatic infertile women show hyperprolactinemia. In such patients fertility may be promoted with long-term use of dopaminergic drugs. The normalized PRL level induced by the treatment allows the occurrence of spontaneous ovulatory cycles or the normalization of the defective luteal phase. Treatment should be continued for at least one year since half of the pregnancies occurring during dopaminergic therapy start after the first 6 months of drug assumption. An ovarian stimulation with gonadotropin and the pulsatile administration of GnRH may also induce ovulatory cycles and fertility in the infertile hyperprolactinemic patients.Hyperprolactinemia either, due to hypothalamic dysfunction, as well as the presence of PRL secreting adenoma usually improves after delivery.     

Results of a prepartal monitoring program in twin pregnancies

152 multiple pregnancies were examined retrospectively. In one group (A) of 59 multiple pregnancies was no therapy, whereas in the other one (B) of 93 multiple pregnancies the duration of pregnancy was prolonged by an early diagnosis using ultrasound, taking out of working process, cerclage in the 16th to 20th gestational week, compulsory hospitalisation (29th to 36th gestational week) and tocolysis and induction of labor in the 39th gestational week. By this duration of pregnancy could be prolonged about 17 days. 36th week could be reached by 82 per cent of the so tended pregnancies, 37th week by 35 per cent. Comparing the two regimes the mean birth weight of twin I increased significantly from 2170 to 2420 g and of twin II from 2210 to 2390 g. The percentage of neonates over 2000 g rose from 53,4 per cent to 72.8 per cent. Perinatal mortality decreased from 8.4 per cent to 3.3 per cent.     

Human chorionic gonadotropin rise in normal and vanishing twin pregnancies

OBJECTIVE: The purpose of the study was to describe and to compare the rate of rise of human chorionic gonadotropin (hCG) in vanishing twin and normally progressing twin pregnancies during the first trimester. DESIGN: All patients with twin pregnancies between 1985 and 1989 were prospectively studied. Human chorionic gonadotropin was measured one to three times per week between days 12 and 52 after luteinizing hormone (LH) surge or day of hCG administration (day 0). Pelvic ultrasound (US) was performed weekly beginning on day 24. SETTING: The study was performed at Rush-Presbyterian-St. Luke's Medical Center in an academic private practice setting of the Section of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology. PATIENTS: Forty patients who conceived after treatment of infertility and who had two gestational sacs on US examination were included in the study after the following criteria were met: (1) both sacs progressed to exhibit a fetal pole and (2) day of LH surge and/or day of hCG administration was known. MAIN OUTCOME MEASURE: The rate of rise of hCG was slower in vanishing twin pregnancies than in normally progressing twin gestations for the entire time period studied (P less than 0.05). RESULTS: A vanishing twin occurred in one third of the twin pregnancies. Forty-six percent of these losses occurred after fetal heart activity had been established. CONCLUSIONS: Vanishing twin phenomenon occurred in a large proportion of twin pregnancies in this infertility population. Fetal heart activity was not a reliable predictor of continuing fetal viability in early twin gestations. Vanishing twin conceptions were characterized by a slower rate of rise of hCG than normally progressing twin pregnancies.     

The incidence of complications during pregnancy after treatment of hyperprolactinemia with bromocriptine in patients with radiologically evident pituitary tumors.

The course of pregnancy achieved after bromocriptine therapy is described in nine patients with radiologically evident prolactin-secreting pituitary tumors. In six patients no complications occurred. No changes in sellar size or secondary endocrine deficiencies developed. In three patients, however, complications developed between the 22nd and 24th weeks of pregnancy. Despite prior external pituitary irradiation, one patient developed transient bitemporal hemianopsia and one patient had apoplexy of the pituitary tumor with transient paresis of the left abducens nerve. A third patient developed parasellar expansion of the pituitary tumor with bone destruction and paresis of the right abducens and oculomotor nerves. After transsphenoidal surgery the paresis of both nerves disappeared. Microscopically, the tissue removed at surgery was a chromophobe adenoma with focal fibrosis and calcifications without recent hemorrhages. In the course of more than 100 pregnancies achieved in The Netherlands after bromocriptine therapy, five patients reportedly developed complications of the pituitary tumor. At present, patients in whom complications can be expected cannot be predicted by the size or configuration of the sella turicica or the magnitude of elevation of the plasma prolactin level. In two patients external pituitary irradiation did not prevent complications during pregnancy.     

Brain damage to the survivor within 30 min of co-twin demise in monochorionic twins

Single fetal death in a twin pregnancy in the late second or early third trimester is associated with significant morbidity and mortality rate in the surviving co-twin, especially in monochorionic twin pregnancies. The common causes are twin-to-twin transfusion syndrome, chromosomal abnormalities, and congenital anomalies of the fetus or anomalies of the umbilical cord-placenta. Here we report a case of monochorionic twin pregnancy in which one fetus had a single umbilical artery (SUA) while the co-twin had two umbilical arteries. The twin with SUA died in utero at the 30th week of gestation and the other fetus was delivered by cesarean section immediately due to fetal distress diagnosed by cardiotocography. Disseminated intravascular coagulation and multicystic encephalomalacia have been observed in the surviving neonate. This case and review of the literature suggest that neurologic complication rates are also increased in monochorionic twin pregnancies with single fetal demise despite the immediate delivery as in our case.     

Early pregnancy wastage: the role of repetitive human chorionic gonadotropin supplementation during the first 8 weeks of gestation.

OBJECTIVE: To determine if repetitive administration of hCG causes decreased pregnancy wastage rates in patients who are at a high risk of luteal inadequacy. DESIGN: Ovulation induction using human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or clomiphene citrate (CC) is associated with luteal phase defects that may cause increased pregnancy wastage. An increased risk of abortion exists also in pregnancies in patients with previous repeated miscarriage, women older than 37 years, and various causes of infertility such as hyperprolactinemia. Because the presumed common denominator to the increased rate of pregnancy wastage in all these cases is luteal dysfunction, repetitive hCG administration, 2,500 U two times weekly, was carried out between the 4th and 8th week of gestation in 249 cases of ovulation induction and/or previous abortions, whereas 198 gestations served as controls (no hCG administration). RESULTS: In the hCG treatment group, 43 ended in miscarriage (17.3%) versus 97 abortions in the control group (49%, P less than 0.01). In 160 cases of hMG/hCG generated gestations, 94 received hCG and 66 did not. The pregnancy wastage rates were 21.3% and 42.4%, respectively (P less than 0.05). In 144 cases of CC/hCG-induced pregnancies, 95 received hCG and 49 served as controls. The respective abortion rates were 15.8% and 44.8% (P less than 0.01). The remaining 143 spontaneous conceptions occurred in infertile patients with previous repeated abortions. In 60 of these conceptions, hCG was administered during the first 4 weeks of gestation and 83 cases served as control. The pregnancy wastage rates were 13.3% versus 56.6%, respectively (P less than 0.001). CONCLUSION: Repetitive administration of hCG during the early gestation in cases that are at high risk of luteal inadequacy may significantly decrease the pregnancy wastage rate.     

Pituitary tumors and pregnancy.

This paper contains a review of the natural history of pituitary tumors in nonpregnant and pregnant patients. Data were drawn from previously published reports and from responses to a questionnaire and were analyzed by life-table techniques. Follow-up of 62 nonpregnant patients with untreated pituitary tumors with and without visual field changes revealed a median time to treatment of 15 1/2 years and similar, relatively constant hazard functions. In 91 pregnancies occurring in 73 women with previously untreated pituitary tumors, ovulation had occurred spontaneously in 9 per cent, headache occurred in 23 per cent, and visual disturbances in 25 per cent with 61 per cent remaining asymptomatic. In those patients who developed symptoms, median time to headache was 10 weeks and to visual disturbance, 14 weeks. The hazard functions were relatively constant and similar. The relative risk of developing symptoms is independent of whether or not the first or second pregnancy occurred in the presence of the pituitary tumor. Of the pregnant patients with previously untreated pituitary tumors, 30 per cent required surgery or radiation therapy. Median time to treatment was 19 weeks. None of the 69 pregnant women without pituitary therapy had permanent sequelae. Only four patients who underwent surgery or received radiation treatment developed permanent symptoms and none was serious. In 78 pregnancies occurring in 73 women with previously treated pituitary tumors, headache occurred in 4 per cent and visual disturbances in 5 per cent. Only one patient required therapy. Treatment during pregnancy results in significantly increased prematurity rates but unchanged abortion and perinatal mortality rates. Small pituitary tumors do not constitute a contraindication to either induction of ovulation or pregnancy.     

Spontaneous pregnancy in women with a prolactin-producing pituitary adenoma

The occurrence of spontaneous pregnancy in patients with amenorrhea-galactorrhea, hyperprolactinemia, and radiographic evidence of a pituitary tumor is unusual. We present here two patients who conceived spontaneously. One had an uneventful pregnancy. Following delivery, transsphenoidal pituitary surgery was performed, confirming the presence of a prolactin-producing adenoma. The second patient had an early pregnancy termination (at 12 weeks of gestation). These patients provide evidence that ovulation and pregnancy can occur in spite of elevated prolactin levels.     

Value of luteinizing hormone-releasing hormone testing in bromocriptine treatment of amenorrhea and hyperprolactinemia in patients with pituitary tumors.

The results of bromocriptine treatment in 13 patients with radiologically evident pituitary tumors are described. A menorrhea was present in all patients, hyperprolactinemia in 12 of the 13 patients, and acromegaly in 3 patients. Five patients have previously been treated surgically and by radiotherapy because of suprasellar extension of the adenoma. Plasma prolactin levels after one single dose of 2.5 mg of bromocriptine were found to have no predictive value as to the dosage needed for treatment, whereas the plasma gonadotropin response after the administration of luteinizing hormone-releasing hormone appeared to be predictive with respect to the return of ovulation during bromocriptine therapy.     

Pregnancies caused by in vitro fertilization in cycles, stimulated with human hypophyseal gonadotropin and chorionic gonadotropin

In a program of in vitro fertilization, laparoscopies for oocyte aspiration were performed on 35 patients receiving human pituitary gonadotropin (hPG) and human chorionic gonadotropin (hCG). Of the 122 preovulatory oocytes which were recovered from these patients, 44 (36%) were fertilized and cleaved, and were transferred. 144 immature oocytes were collected, and attempts were made to mature these in vitro. 40 oocytes (28%) could be fertilized and cleaved, and were transferred. Eight pregnancies resulted from 32 embryo transfers (25%), and 22,9% from laparoscopies, respectively. Of the eight pregnancies, there were three preclinical abortions and two clinical abortions, and three patients are well along in the pregnancy. Among the three patients there is one twin pregnancy.     

Therapeutic and eugenic termination of pregnancy: technical indications

131 therapeutic and eugenic abortions performed at the Saint-Antoine Hospital in Paris between July 1977 and December 1984 are analyzed. There were 6.5 therapeutic and eugenic abortions and 2106 abortions for social reasons per 1000 live births during the period. The number of therapeutic and eugenic abortions per complete year has ranged from 11 to 19 except for an unexplained peak of 32 in 1983. 30 of the 131 abortions were for maternal indications, including 8 cases each of psychiatric and cardiac disorders, 4 each of digestive and respiratory disorders, and 1 each of ophthalmologic disorder, breast cancer, hydronephrosis, hemolytic anemia, cerebral motor infirmity, and rape. Among fetal indications, there were 38 cases of chromosomal anomalies, 29 of fetal malformations, 18 of infection including rubeola and toxoplasmosis, 9 of irradiation early in pregnancy, and 7 of presumed risks of medications. The number of abortions for fetal malformations diagnosed by sonography has been steadily increasing. 25 of the abortions for maternal indications were performed before the 15th week of gestation. All except 1 abortion for chromosomal anomalies diagnosed by amniocentesis occurred around 21 weeks of pregnancy. All except 3 abortions for fetal malformations occurred between 15 and 28 weeks. 6 for infection occurred before and 12 after 15 weeks of pregnancy. All abortions for irradiation and 6 of 7 for presumed risks of drugs occurred before 15 weeks. The abortion technique utilized was a function of gestational age and the year the abortion occurred. All 32 abortions before 12 weeks were by dilatation and aspiration. 7 hysterotomies were performed in cases of scarred uterus or failure of abortifacient agents. Intraamniotic injection of saline solution was replaced in October 1980 by use of prostaglandin F2 alpha, which was used until March 1983 when prostaglandin E2 was substituted. The data show a clear decline in the number of abortions for maternal indications, which are expected to decline even further because of use of contraception and improved ability to manage high risk pregnancies.     

Male hyperprolactinemia:effects on fertility.

Male hyperprolactinemia was detected in 4% (7 of 171) of infertile men. In seven patients with excessive serum prolactin concentrations, the clinical manifestations were infertility, hypogonadism, impotence, and galactorrhea and the etiologic factors were pituitary adenoma, hypothalamic dysfunction, drug use, and idiopathic. The testes and prostate were small or normal and the semen analysis revealed low semen volume, normal or low sperm count, and normal or impaired sperm motility. The testicular biopsy showed normally preserved seminiferous tubules with normal or decreased spermatogenesis and damaged or fibrotic seminiferous tubules among normal ones. Patients with hyperprolactinemia were investigated by sellar polytomography, visual field examinations, and hormone assays. Treatment with bromocriptine (Parlodel) gave satisfactory results in all patients. The use of bromocriptine with human menopausal gonadotropin and human chorionic gonadotropin was beneficial in treating hypogonadotropic hypogonadism with hyperprolactinemia.     

9例多胎妊娠合并胎儿染色体异常患者的产前诊断和治疗

目的探讨多胎妊娠合并胎儿染色体异常的产前诊断方法及选择性减胎术定位方法。 方法选取2012年1月至2013年12月就诊于广州医科大学附属第三医院9例多胎妊娠合并胎儿染色体异常患者的临床资料,采用回顾性研究方法对其产前诊断方法、染色体异常情况、选择性减胎术的方法及妊娠结局进行分析。 结果9例患者中3例为三胎妊娠,6例为双胎妊娠。(1)产前诊断：①超声检查：9例患者早孕期行超声检查,均提示存在胎儿颈项透明层(nuchal translucency, NT)增厚,孕中期超声检查提示有6例患者存在胎儿结构异常,包括颈部囊肿、心脏异常、外生殖器畸形、足内翻、全身水肿等;②染色体检查：5例胎儿21-三体综合征,1例Turner综合征,1例染色体微缺失,1例染色体重复,1例双胎染色体异常。(2)治疗及妊娠结局：9例患者中7例患者行选择性减胎术治疗,1例流产,3例早产(新生儿均存在并发症),3例足月分娩(新生儿均未见异常);2例患者拒绝减胎,1例于孕中期自然流产,1例于孕35^＋周剖宫产分娩(1胎儿为21-三体综合征,另一胎儿为健康儿)。 结论多胎妊娠应注重早孕期染色体筛查,确诊宫内胎儿染色体异常的患者可在超声引导下行选择性减胎术治疗。