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.     

Outcome and long-term effects of pregnancy in women with hyperprolactinaemia.

Twenty-four women with high circulating prolactin became pregnant on 39 occasions, of which 32 ended in delivery. Sixteen patients showed radiological evidence of pituitary tumour, 6 exhibited a normal CT and 2 had an empty sella. The pregnancies were induced in 4 patients after successful pituitary surgery, in 3 after surgery and medical treatment, and in the rest by bromocriptine (16) long-acting repeatable bromocriptine (1) and methergoline (1). No major complications related to hyperprolactinaemia or its treatment were observed during pregnancy in the patients or offspring. Prolactin after pregnancy was lower than before (basal 95 micrograms/l, after 1st pregnancy 38 micrograms/l P < 0.002, after 2nd pregnancy 24 micrograms/l P < 0.005 compared to basal prolactin); this prolactin reduction tended to be greater in the 9 multiparous patients, but did not attain statistical significance, probably because the number of multiparous patients was too small. A new empty sella developed after delivery in 4 women and persisted in another 2, all of which were medically treated; prolactin fell in all 6 cases normalizing in 3; 4 of these patients had undergone two or more pregnancies. The mean period of follow-up from the last pregnancy was 41.6 months (8-101). These data suggest that pregnancy may hasten a tendency to spontaneous improvement of hyperprolactinaemia, and multiparity may be beneficial in this way.     

Spontaneous abortion after amniocentesis in women with a history of spontaneous abortion

The incidence of spontaneous abortion after amniocentesis (19 to 28 weeks gestation) in women who have had previous spontaneous abortions is compared with the rate in women who have not had previous spontaneous abortions. The outcome of the pregnancy after amniocentesis and the previous history of spontaneous abortion is reported for 691 pregnancies. The rate of spontaneous abortion after amniocentesis was found to be significantly higher in women who had one or more previous spontaneous abortions, 12/238 (5 per cent), than in women who did not, 6/453 (1.3 per cent). In women who reported two or more previous spontaneous abortions, the rate was 7/81 (8.6 per cent). No statistically significant effect of maternal age or gravidity was detected. The incidence of spontaneous abortion after amniocentesis was greater in the three weeks following the procedure (three for each of the three weeks) than in the subsequent seven weeks (nine for seven weeks).     

Ultrasound evidence of early pregnancy failure in patients with multiple conceptions.

I report a review of 1500 pregnant patients: 30 of them (or 1 in 50) were thought to have multiple pregnancies when examined by ultrasound in the first trimester. Only 14 of the 30 patients (46.7 per cent) produced live infants: 13 twins and one set of triplets. Twelve (40 per cent) had bleeding in early pregnancy and 11 of these had a spontaneous abortion. Five of seven patients found to have a normal pregnancy and a coexistent blighted ovum, ultimately delivered a single live infant.     

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.     

Endometrial aspiration in fertility control. A report of 500 cases.

Outpatient endometrial aspiration was offered to patients who suspected that they were pregnant, but were within 5 to 21 days after failure of expected menstruation and had a uterus of normal size on pelvic examination. This is a report of 500 consecutive cases treated between September, 1973, and April, 1975. Histologic examination of the aspirated tissue was obtained on all 500 cases (100 per cent). Follow-up examination and urine pregnancy was obtained on 407 patients (81.4 per cent). Histologic evidence of pregnancy was obtained in 323 patients (64.6 per cent). Complications were limited to five infections (1 per cent), only one of which led to hospitalization of the patient, and failure to completely evacuate the pregnant uterus in 39 patients (12.1 per cetn of the 323 pregnant). Thirty-four of these had the uterus emptied by a second outpatient procedure and five patients were hospitalized to complete their abortion.     

Clomid therapy for anovulatory infertility

The results of Clomid treatment of 81 infertile patients seeking pregnancy are reported: 60.5 per cent of patients ovulated and 25.9 per cent became pregnant. No unusual side effects of therapy were noted. In general, patients who were oligoovulatory or amenorrheic with evidence of estrogen production had successful responses. These results are comparable to other series. The disparity between ovulation and pregnancy rates in all these studies is noted and a case indicating a Clomid-induced non-corpus luteum source of progesterone production is included.     

Hyperprolactinemia and hypophyseal tumors--results of treatment with bromocriptine

Forty-one patients with hyperprolactinemia are presented. They were divided into two groups. In the first group, 11 or 27% women had radiological evidence of a pituitary tumour. Seven of 11 patients conceived by means of the bromocryptine treatment. The visual impairment in one patient in the tenth week of pregnancy disappeared after the re-institution of bromocryptine. The values of prolactin in this group varied between 4000 and 7000 mIE/ml. In the second group, 30 or 73% women were without radiological evidence of a pituitary tumour. The values of prolactin in this group ranged from 1200 to 5000 mIE/ml. Fourteen of 30 patients conceived by means of the bromocryptine treatment.     

Hyperthyroidism complicating pregnancy: results of treatment by antithyroid drugs in 77 pregnancies

Seventy-seven pregnancies (79 infants) complicated by hyperthyroidism were seen at three Dublin Maternity Hospitals during a 25 year period. Hyperthyroidism was diagnosed following conception in 14 pregnancies. Treatment was with carbimazole alone in 73 pregnancies, in a usual dose of 5 to 10 mg daily. The total fetal loss was 15.2 per cent with a perinatal loss of 5.1 per cent. The perinatal loss in patients treated with carbimazole alone was 4.1 per cent (excluding one death due to congenital malformation). Four infants (5.1 per cent) had goitre and 57 (85.1 per cent) of the surviving infants were above the 25th centile for gestational age. Spontaneous premature labour occurred in 7 pregnancies (9.1 per cent). There was a relative excess of infants with a birth weight less than the 25th centile, of neonatal goitre and premature labour after pregnancy in which treatment was started following conception. Hyperthyroidism complicating pregnancy can be treated effectively with antithyroid drugs given alone and in the minimal effective dose.     

Estradiol metabolism in pregnant and nonpregnant women

After the intramuscular injection of tracer doses of estradiol-6,7-H³ to 1 nonpregnant and 4 pregnant women, the radioactivity present in the blood and various maternal and fetal tissues was determined, and the tritiated urinary excretion products were measured and identified. The levels of tritium in the fetal circulation were 50 to 75 per cent of those in comparable maternal blood, indicating that the steroid readily crosses the placental barrier. Approximately 2 hours after estradiol injection, the uterus and subcutaneous fat of the nonpregnant, but not of the pregnant, patients showed high levels of radioactivity. In the fetus, the pituitary possessed a higher tritium content than the blood, while the liver, gall bladder, and upper intestine showed high levels of radioactivity, suggesting hepatic clearance of estrogen from the fetal circulation.Three patients in whom pregnancy was of 15 weeks' or greater duration excreted a much smaller amount of the administered tritium as urinary metabolites than did the 12 weeks pregnant or nonpregnant patients. The latter 2 individuals excreted radioactivity principally as estrone, especially in the first 12 hours after injection. The 3 patients with further advanced pregnancies excreted large amounts of radioactive estriol and other more polar steroids with only small quantities of estrone, and continued to do so even after the ovaries, placenta, and fetus were removed. It is suggested that, between the twelfth and fifteenth weeks of pregnancy, adaptive changes take place in steroid metabolism by maternal tissues, resulting in enhanced conversion of estradiol to estriol.     

Prenatal screening and diagnosis of neural tube defects in England and Wales in 1985

A survey was carried out to determine the effect of prenatal screening and therapeutic abortion on births in 1985 with anencephaly and spina bifida in England and Wales. Maternal serum alpha-fetoprotein tests were done on 399,288 women (60 per cent of pregnant women): 4 per cent were reported as being screen-positive and 1 per cent had an amniocentesis. An estimated 534 pregnancies associated with anencephaly were terminated and an estimated 445 pregnancies associated with spina bifida (but without anencephaly) were terminated. Most (63 per cent) of the anencephalic pregnancies were first suspected from an ultrasound examination; 57 per cent of the spina bifida pregnancies were first suspected from a positive maternal serum alpha-fetoprotein test, 35 per cent by ultrasound, and the remaining 8 per cent by other means. The birth prevalence of anencephaly declined by 94 per cent between 1964-1972 and 1985, but when the terminations of pregnancy on account of having a fetus with anencephaly are added to the births the decline in prevalence was only 50 per cent. The birth prevalence of spina bifida declined by 68 per cent over the same period but when the terminations were added to the births the decline in prevalence was only 32 per cent. Among births with anencephaly 66 per cent had had no screening or diagnostic tests in early pregnancy, but in those that did nearly all were positive--usually in twin pregnancies where one fetus was affected but not the other. Among births with spina bifida, 48 per cent had no tests and in those that did the results were mainly negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective study of primary cytomegalovirus infection in pregnant women

During a four year study, sera were obtained from 5575 women attending for antenatal care and 3188 (57.2 per cent) were shown to possess complement fixing antibodies to cytomegalovirus (CMV). A total of 1608 seronegative women were followed to term and 14 (0.87 per cent) primary CMV infections occurred in either the second or third trimester. Transplacental spread of CMV occurred in 3 out of 12 (25 per cent) of the 14 babies born to infected mothers. All 14 babies were apparently normal at birth but short term clinical follow-up has already revealed that one child has impaired hearing whilst another is microcephalic. The women were also monitored serologically throughout pregnancy for evidence of rubella infections. Only 12 infections were detected and 7 of these occurred during the large rubella epidemic of 1978. Of the 10 pregnancies which were allowed to proceed to term, transplacental spread of rubella virus occurred in 1 out of 7 (14 per cent). During this study period, CMV infections occurred as frequently as did rubella infections. We therefore conclude that, apart from those years when extensive epidemics occur, many more pregnant women are infected with CMV than with rubella virus.     

Maternal smoking habits and Down's syndrome

Two series of pregnancies were studied to investigate the relationship between maternal smoking and the risk of fetal Down's syndrome. In the first series, ascertained in the 1960s, in which smoking habits were determined after the outcome of pregnancy was known, the proportion of smokers (47 per cent) among the 461 women whose pregnancies ended in the birth of an infant with Down's syndrome was similar to that in the 461 controls (46 per cent) who had pregnancies affected by other congenital disorders. In the second series, ascertained between 1973 and 1984, smoking habits were determined by measurement of cotinine in antenatal serum samples that were routinely collected and stored or, if a serum sample was not available, from information in the antenatal notes. In this series, the proportion of smokers (14 per cent) among the 91 women who had pregnancies associated with Down's syndrome was lower than that among 413 controls (19 per cent), though this was not statistically significant. Collectively, our results provide no evidence for an association between fetal Down's syndrome and smoking. Other published studies found a deficit of smokers among women who had pregnancies associated with Down's syndrome. This may be partly due to some studies not taking adequate account of maternal age (older women are more likely to have had a Down's syndrome pregnancy but are less likely to be smokers) and partly due to the greater tendency for positive findings to be published than negative ones.     

The effects of pregnancy on patients with hyperprolactinemia

Seventy women with amenorrhea with or without galactorrhea associated with high serum prolactin levels and radiologic evidence of pituitary tumors were treated with transsphenoidal tumor resection. The prolactin level was measured in 29 patients before pregnancy, at 3 months post partum or cessation of lactation, and at 6-month intervals thereafter. The results were compared to those of 18 patients who had hyperprolactinemia but no demonstrable radiologic evidence of a pituitary tumor and who responded to bromocriptine and conceived. Our investigations showed that operation resulted in normalization of serum prolactin levels in 74% of patients. Forty of the 49 patients less than 36 years old conceived (80%). Five of 29 patients who were studied before and after operation as well as after delivery showed an increase in serum prolactin levels post partum and persistent amenorrhea suggesting recurrence. Six of the 18 patients who became pregnant after bromocriptine also showed a significant rise in serum prolactin levels above the treatment level. None of the patients in the two groups developed visual changes or symptoms or radiologic changes during pregnancy. These results showed that transsphenoidal operation has a high incidence of success, but some patients may show a rise of serum prolactin levels and persistent amenorrhea after pregnancy or passage of time, suggesting recurrence. Some patients who become pregnant after bromocriptine therapy may have further rises in prolactin greater than pretreatment levels. Follow-up of these patients is indicated.     

Role of detection of alphafoetoprotein in serum of pregnant women with risk of abortion (author's transl)

Alpha, foetoprotein (AFP) was radio-immunologically determined in the serum of 109 pregnant women with imminent abortion and of 220 clinically intact women who were between the sixth and 22nd weeks of pregnancy. -- AFP values were found to be normal, within limits between 0.5 m and 2.0 m, in 84.8 per cent of the clinically intact women and in 83.3 per cent of those pregnant women with imminent abortion and favourable completion of pregnancy. Values were above or below normal in 73.3 per cent of those pregnant women who failed to complete pregnancy with good success.     

Visual and neurological disturbances accompanying with pregnancies of hyperprolactinemic patients

Twenty-three hyperprolactinemic infertile cases become pregnant after surgical treatment and/or bromocriptine administration, and 18 of them accomplished normal full-term deliveries. Serial ophthalmological examination which had been performed monthly throughout pregnancy revealed that four cases bearing pituitary adenomas developed visual disturbances which manifested themselves in the latter part of gestational period. The objective signs detected in these cases were bitemporal hemianopsia, temporal and nasal visual defects and the disappearance of central isopter. Another patient with microadenoma complained of headache at 16 weeks of gestation and it became more severe as gestation progressed. Bromocriptine (1.25 mg/day) was effective in diminishing this symptom. Although all these cases recovered from visual disturbances and headache after delivery, two of them were operated on transsphenoidally when radiological evidence of pituitary enlargement was found in the postpartum period. It is generally accepted that nearly 20% of hyperprolactinemic patients have pituitary adenomas. In view of the limited accuracy of techniques used in diagnosing pituitary tumor, it is legitimate to postulate that most hyperprolactinemic infertile patients have microadenoma to some extent. For this reason, a detailed follow up of visual field and neurological signs throughout pregnancy of hyperprolactinemic patients is important in early detection of changes in pituitary size.     

Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age.

One hundred and fifty-one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy.     

SQ 20,881: effect on eclamptic--pre-eclamptic women with postpartum hypertension

The renin-angiotensin system has been implicated in the genesis of pre-eclampsia. To avoid fetal toxicity, five women were studied who developed hypertension, proteinuria, and edema in the last trimester of pregnancy and whose BP elevation persisted immediately postpartum. At about 6 hours after delivery the CE enzyme inhibitor (SQ 20,881) was given in incremental doses ranging from 0.25 to 3.0 mg. per kilogram intravenously, before and after diuresis with furosemide, 40 mg. intravenously. BP was measure every 2 minutes and PRA and angiotensin II concentration before treatment, 30 minutes after 0.25 to 0.30 mg. per kilogram, and 30 minutes after 2.0 to 3.0 mg. per kilogram. Echocardiographic assessment of CI and PVR was performed before treatment and after a maximum dose in three patients. Before diuresis, CE blockade had no effect on heart rate, BP, CI, PVR, or PRA, regardless of whether the patient was in positive or negative fluid balance or was sodium loaded or restricted over the preceding 24 hours. Angiotensin II fell by 77 and 10 per cent, respectively, after 0.25 mg. per kilogram was given to two patients, but rose slightly in the other three patients, then fell an average of 46 per cent after 1.0 to 3.0 mg. per kilogram were given. After diuresis, 1.0 mg. per kilogram resulted in a 24 per cent fall in BP which persisted for 3 hours in two patients and a 14 per cent fall which lasted for 30 minutes after 1.0 or 3.0 mg. per kilogram in a third patient. It is concluded that the BP elevation which persists after delivery in certain patients with pre-eclampsia is not angiotensin II dependent.     

Transabdominal villus sampling in early second trimester: a safe sampling method for women of advanced age

Transabdominal chorionic villus sampling (TA-CVS) was performed in 707 viable singleton pregnancies to exclude chromosomal abnormalities. Maternal age ranged between 36 and 49 years (mean 37.9 years); gestational age varied between 10.2 and 18.3 weeks (mean 13.3 weeks). In 639 women (90.4 per cent), a sufficient amount of chorionic tissue (greater than or equal to 10 mg) was obtained after one needle insertion; in 66 women (9.3 per cent) two insertions were needed. An abnormal chromosome pattern was established in 19 cases (2.9 per cent). Vaginal bleeding or spotting within 28 days after TA-CVS occurred in 11 cases (1.5 per cent). The completed follow-up of 678 chromosomally normal pregnancies showed an overall fetal loss rate of 2.6 per cent before 28 weeks. The overall perinatal mortality was 0.9 per cent. When relating fetal loss to gestational age at TA-CVS, this was 6.6 per cent in women sampled before 12 weeks against only 1.8 per cent after 12 weeks. At the same time, the percentage of fetal loss occurring within 2 weeks following the procedure was 75 and 30 per cent, respectively. It is suggested that these data reflect the decline in spontaneous abortion rate during this particular period of pregnancy. It is concluded that TA-CVS is an effective procedure which, when performed after the natural decrease of fetal loss, appears to be a safe option for women of advanced maternal age.     

Gamete intrafallopian transfer in women who had ectopic pregnancy previously.

Eighty-seven women who had previously had ectopic pregnancy underwent 111 gamete intrafallopian transfers (GIFT). Forty-one women had moderate or severe pelvic adhesions, eight had mild pelvic adhesions, and 18 had had the fallopian tubes surgically repaired. The remaining 20 women had no obvious pelvic abnormality except for the absence of one fallopian tube. After stimulation of superovulation, between two and 22 oocytes were retrieved and two to four were transferred into the fallopian tubes after careful assessment of their condition. Twenty-eight pregnancies were achieved (25.2% per cycle), with 23 live births (20.7% per cycle), four abortions (14.3% of all pregnancies), and one ectopic pregnancy (3.6% of all pregnancies, 0.9% per cycle). This experience shows that GIFT can safely produce a reasonable pregnancy rate in carefully selected women who have had ectopic pregnancy.