Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency.

Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33 CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery. Results. Patients had larger median clitoral lengths (10.0 mm [range 2-30] versus 3.5 [2-8], P < .001), shorter vaginal length (121 mm [100-155] versus 128 [112-153], P = .12), lower uterine volumes (29.1 ml [7.5-56.7] versus 47.4 [15.9-177.5], P = .009), and higher ovarian volumes (4.4 ml [1.3-10.8] versus 2.8 [0.6-10.8], P = .09) than controls. Satisfaction with genital appearance was lower and negatively correlated to degree of initial virilisation (r(s) = ≤-0.39, P ≤ .05). More patients had never had intercourse (P = .001), and age at 1st intercourse was higher (18 yrs versus 16 yrs, P = .02). Conclusion. Despite overall acceptable cosmetic results, reproductive outcomes were suboptimal, supporting that multidisciplinary teams should be involved in adult follow up of CAH patients.

Growth hormone treatment during pregnancy in a growth hormone-deficient woman.

Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 25-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she became pregnant after donor insemination. The GH treatment was continued until variant GH production from the placenta was evident. Serum levels of GH, IGF-I and IGFBP-3 were measured monthly during pregnancy after 3 days off GH therapy. Abdominal ultrasound was performed five times. Hormonal levels were measured immediately after delivery and during the following days. Serum GH and IGF-I levels increased during the second half of pregnancy; serum IGFBP-3 remained constant throughout pregnancy at a normal level. Serum levels of GH fell within 1 h after delivery, and levels of IGF-I and IGFBP-3 decreased into the range of GH-deficient women 4 days after. The fetal biparietal diameter increased normally, and birthweight was 3.564 kg, length 52 cm. No adverse events were recorded. We conclude that the role of GH replacement during pregnancy of GH-deficient women should be investigated further.

Perinatal outcome after in vitro fertilisation.

A prospective series of 90 consecutive pregnancies (70 singleton, 16 twin and 4 triplet pregnancies) resulting in births of 114 infants after in vitro fertilisation (IVF) at Rigshospitalet were compared to a control group of pregnancies and deliveries in 70 non-IVF infertility patients with singleton pregnancies and 20 women with normal fertility with twin (n = 16) or triplet (n = 4) pregnancies. No differences in the incidence of third trimester pregnancy complications, abnormal fetal karyotypes or malformations were found. The number of women with spontaneous onset of labor and the gestational age at delivery were similar in the IVF and control groups. In singleton deliveries, the birth weight was lower (p < 0.025) in the IVF group (median 3145 g, range 890-4300 g) than in the control group (3399 g, 2592-4850 g), whereas in multiple gestation similar birth weights were found in the IVF and control groups. We conclude that the birth weight in singleton deliveries after IVF is lower than the birth weight in infertility patients treated differently. The cause of this difference remains obscure.

[Fertilization in vitro. A review over the medical indications and suggestion to unified guidelines for public fertility clinics in Denmark]. / In vitro fertilisering. En oversigt over medicinske indikationer og forslag til foelles retningslinier ved de offentlige danske fertilitetsklinikker.

Medical indications for in vitro fertilization and embryo transfer (IVF-ET) internationally and in Denmark are reviewed. Reports from large international centres document that tubal infertility, unexplained infertility, endometriosis and male infertility are equally good indications for IVF. Traditionally, tubal infertility has been the only medical indication qualifying for IVF treatment within the National Health Service in Denmark. Thus, in this country, couples with unexplained and male infertility and with endometriosis have to pay up to 25,000 D.Kr. per IVF-ET treatment in private fertility clinics. Since there is no scientific basis for this discrimination, it is urged that the present rules are changed, so that couples with unexplained and male infertility and endometriosis are also allowed IVF treatment free of charge in the public fertility clinics.

[Ovum donation. A review of and a suggestion to unified guidelines for treatment at public fertility clinics in Denmark]. / Aegdonation. En oversigt samt forslag til foelles retningslinier for behandling ved de offentlige danske fertilitetsklinikker.

The most common indication for oocyte donation is ovarian insufficiency due to premature menopause or resistant ovarian syndrome and ovarian dysgenesis with either normal or abnormal (e.g. Turner's syndrome) karyotype. In Denmark, oocyte donation must be anonymous, and the donors have to be other infertile patients undergoing in vitro fertilisation (IVF), treatment. It is suggested, that the National Health Service offers oocyte donation to hypergonadotropic women with ovarian insufficiency, as well as to a few other groups who fulfil the criteria for IVF treatment, but where this treatment cannot be completed. Oocyte donors must be less than 35 years old, physically and mentally healthy and without major genetic diseases in the family. The donor must be screened for HIV, hepatitis, syphilis, chlamydia and gonorrhoea. We propose that those patients who have more than six oocytes aspirated, allowing "surplus" oocytes to be donated. It is also proposed that the departmental order from the Ministry of Health be changed, so that normally fertile women are allowed to donate oocytes. Oocyte donation should be reported to a central authority.

[Freezing of human embryos. A review of and a suggestion to unified guidelines for treatment at public fertility clinics in Denmark]. / Nedfrysning af menneskelige aeg. En oversigt samt forslag til faelles retningslinier for behandling ved de offentlige danske fertilitetsklinikker.

In Denmark, legislation has made cryopreservation of human oocytes and embryos possible since October 1992. The legislation is reviewed. Cryopreservation of embryos constitutes a significant improvement of infertility treatment. The number of oocyte pick-ups and the number of embryos transferred can be reduced without compromising the total likelihood of success of in-vitro fertilization (IVF) treatment. According to Danish law, frozen embryos can only be stored for one year. This limit will interfere with patient expectations in numerous cases, and the time limit should be expanded. Moreover, freezing of embryos should be allowed in connection with oocyte donation programmes.

[Human serum albumin as the protein source in culture of human oocytes, spermatozoa and pre-embryos]. / Humant serum-albumin som proteinkilde ved dyrkning af humane oocytter, spermatozoer og praeembryoer.

In the treatment of infertility employing in vitro fertilisation and embryo transfer (IVF-EF), oocytes, spermatozoa and pre-embryos are cultured for 48 hours outside the woman's body before they are introduced into the uterus. In addition to the necessary salts, the media in which this culture takes place, also consists of a source of protein. In order to eliminate the variability of patient sera, a prospective, randomized investigation was performed to elucidate whether a well-defined source of protein such as human serum albumin (hSA-hSA 200 mg/ml, Statens Seruminstitute) can replace patient serum as source of protein in the culture of oocytes, spermatozoa and pre-embryos in IVF-ET treatment. The pregnancy rate per transplantation was increased from 30% in the serum group (21 pregnant out of 69 transplantations) to 39% in the albumin group (26 pregnant out of 66 transplantations) but the difference is not significant. On the other hand, the quality of the pre-embryos as assessed by morphological criteria became significantly better and the implantation rate per transplanted pre-embryo was found to be significantly increased in the albumin group. On the basis of this investigation, hSA is recommended as the source of protein, rather than the patient's own serum in the culture of oocytes, spermatozoa and pre-embryos in IVF-ET treatment.

Intrauterine fertilization capsules--a clinical trial.

Treatment of 26 women with tubal infertility was attempted using intrauterine capsules loaded with oocytes and spermatozoa. The stimulation protocol was as used for in vitro fertilization and embryo transfer and consisted of short-term use of Buserelin, human menopausal gonadotropin, and human chorionic gonadotropin. Oocytes were collected by ultrasonically guided transvaginal aspiration, and spermatozoa were prepared by swim-up technique. The gametes were placed in agar capsules 4 hr after oocyte collection, and the capsules were introduced to the uterine fundus using an insertion tube and piston from an intrauterine device. Six complete capsules and parts of two other capsules were expelled. None of the women became pregnant, compared with a pregnancy rate of 21% per aspiration following in vitro fertilization and embryo transfer during the same period.

[In vitro fertilization and embryo transfer. 1. The first 100 pregnancies]. / In vitro-fertilisation og embryotransplantation. 1. De første 100 graviditeter.

The results of treatment of infertility by in vitro fertilization and embryo transfer (IVF-ET) in Rigshospitalet, Copenhagen, are reviewed for 143 patients in whom treatment was completed during the period 1.9.1985-21.2.1988 and for 100 pregnancies during the period 1.9.1985-15.11.1988. Among the 143 patients in whom treatment was completed, 48 became pregnant on one or more occasions as pregnancy occurred in 53 cycles. A total of 44 women delivered 55 infants. There were 35 singleton deliveries, seven twin deliveries and two triplet deliveries. One woman became biochemically pregnant, four aborted before the 12th week of pregnancy an one woman aborted on two occasions in the second trimester. Three women were treated operatively for extrauterine pregnancies. A total of 33.6% of the patients became pregnant, the baby-take-home rate per patient was 30.8%, the pregnancy rate per ET was 23.5% and the delivery rate per transplantation was 19.6%. Non-completed pregnancies per pregnant woman were 20.8%. Only preliminary account of the 100 pregnancies can be given as treatment has not been completed in all of these patients. Among the 100 pregnancies, there were 59 singleton pregnancies, ten twin pregnancies and three triplet pregnancies and 29 pregnancies which were not completed. The age distribution of the pregnant and non-pregnant women (23% over 34 years became pregnant and 53% under 29 years became pregnant) emphasizes the importance of commencing treatment as early as possible.

[In vitro fertilization and embryo transfer. 2. The first 44 deliveries of 55 infants]. / In vitro-fertilisation og embryotransplantation. 2. De første 44 fødsler omfattende 55 børn.

During the period 1.9.1985-21.2.1988, 143 patients commenced and completed treatment with in vitro fertilization and embryo-transfer (IVF-ET) in Rigshospitalet, Copenhagen. Forty-four out of the 143 patients were delivered of a total of 55 infants. There were 35 single deliveries, seven twin deliveries and two triplet deliveries. Seven women were admitted with threatened abortion and three women developed preeclampsia, one of these was severe. On an average, the deliveries occurred in the 38th week of pregnancy and the average weight of the singletons was 3,020 g. Ten women were delivered preterm and seven of the singletons had birth weights under 2,500 g. The frequency of caesarean section was 34% for singleton deliveries and 43% for all of the deliveries. Thirty-one boys and 24 girls were delivered, all of whom had normal karyotypes. One infant had a cleft lip but no other malformations. Three premature infants required brief respirator treatment. All of the infants were thriving on discharge. This material is still too limited to permit drawing of definite conclusions but it suggests, however, just as in other IVT-ET investigations, that the infants are born slightly earlier and weigh slightly less than average neonates, but that they are otherwise normal. In order to illustrate these problems further, the authors have commenced a more extensive prospective investigation with matched control persons.

Regression of endometriosis following shorter treatment with, or lower dose of danazol. Comparison of pre- and post-treatment laparoscopic findings in the Scandinavian multi-center study.

One hundred and sixteen patients with laparoscopically confirmed primary or recurrent endometriosis were treated with danazol, either 600 mg daily for 4 months (group A, n = 76) or 600 mg daily for the first 2 months, followed by 400 mg daily for an additional 4 months (group B, n = 40). The only surgery performed before treatment was biopsies, resection of endometriomas greater than or equal to 3 cm and/or adhesiolysis. The extent of endometriosis before and after treatment was established laparoscopically and recorded by means of a modified AFSrecord as mean additive diameter of implants (mean ADI) in millimeters. This provided a uniform and reproducible quantitative registration for each type and location of endometriotic implant. Both treatment schemes resulted in a highly significant (p less than 0.001) reduction of endometriosis, by 79 and 89% in groups A and B, respectively. However, the reduction in mean ADI was significantly greater (p less than 0.025) in group B which had been treated for a longer period. Moreover, the proportion of patients with extensive pre-treatment lesions (mean ADI greater than or equal to 40 mm) was significantly greater in this group. Active residual endometriosis was found in 21 and 17.5% in groups A and B, respectively. These patients had significantly more extensive endometriosis before treatment. The regression of endometriotic implants was independent of type and/or location, i.e. superficial or scarred; peritoneal, ovarian, or tubal. There was no apparent correlation between the quantitative reduction of endometriosis and amenorrhea versus occasional spotting and/or irregular menstruations.(ABSTRACT TRUNCATED AT 250 WORDS)

The possible prognostic value of serum prolactin increment during pregnancy in hyperprolactinaemic patients.

In 15 hyperprolactinaemic, infertile patients achieving 17 bromocriptine-induced pregnancies, the presence or absence of prolactin (Prl) increment in the 3rd trimester of pregnancy was correlated to the basal Prl levels before treatment and after pregnancy. The hyperprolactinaemic patients revealed a marked heterogeneity in the Prl increment compared to normal women. Five patients showed a pronounced increase in serum Prl during gestation, whereas Prl levels were unaltered or decreased slightly in 10 patients. In the latter group of patients serum Prl was significantly (P less than 0.01) lower after pregnancy than before treatment. Our study indicates that some hyperprolactinaemic patients may benefit from a pregnancy, and that these patients probably can be identified, as they do not show any significant changes in Prl levels during pregnancy.