Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome.

To determine if a 14-bp deletion/insertion polymorphism in the 3'-untranslated region of exon 8 of the gene encoding human leukocyte antigen (HLA)-G in a homozygous form is associated with repeated, unsuccessful in vitro fertilization (IVF) treatments, and with increased risk of recurrent spontaneous abortions (RSA), 29 white women undergoing IVF treatments, 61 RSA women and 93 fertile controls were HLA-G genotype. The HLA-G genotype, homozygous for the presence of the 14 bp sequence in exon 8, was significantly associated with reduced fertility with respect to unsuccessful IVF treatments and increased risk of recurrent miscarriage (combined P < 0.01). The 14-bp insertion/deletion polymorphism is associated with differences in HLA-G mRNA alternative splicing and levels of HLA-G. This might affect a possible immunomodulatory role of HLA-G expression in both the mother and foetus during implantation and pregnancy.

Embryo quality in natural versus stimulated IVF cycles.

BACKGROUND: The impact of controlled ovarian stimulation (COS) on oocyte and subsequent embryo quality remains controversial. In the present study we have compared embryo quality in natural and stimulated cycles in the same group of patients. METHODS: This retrospective study was comprised of patients with a regular menstrual cycle who had IVF after COS using rFSH in a long GnRH agonist protocol. In all stimulated cycles the patients had fresh embryos transferred and surplus good quality embryos cryopreserved. Subsequently the same patients were treated with a modified FER cycle (mFER) where thawing of the frozen embryos was combined with aspiration of the dominant follicle in the natural cycle. The embryo cleavage stage and quality score were compared between the stimulated and the natural cycle for the patients having an embryo in the natural cycle. RESULTS: In 177 cases patients returned for mFER in a natural cycle. Spontaneous ovulation had occurred in 35 cycles. In 17 cycles no oocyte was retrieved at aspiration and in 125 cycles 128 oocytes were aspirated. In the stimulated cycles from these patients we had obtained 950 embryos (cleavage rate 70.4%) versus 85 embryos (cleavage rate 66.4%) (P = 0.34) in the natural cycles. Comparing the embryos in the natural and stimulated cycles in all patients having an embryo in the natural cycle, we found no difference in the distribution between the different cleavage stages. Of the cleaved embryos, 53% in the stimulated cycles had >or=4 cells versus 59% in the natural cycles after 2 days culture (P = 0.31). In the stimulated cycles 61% of the embryos had <10% fragmentation at the time of transfer on day 2, compared to 69% in the natural cycles (P = 0.15). CONCLUSION: The administration of exogenous gonadotrophins was not reflected in cleavage capacity or quality assessment of the resulting embryos.

A prospective study of predictive factors of ovarian response in 'standard' IVF/ICSI patients treated with recombinant FSH. A suggestion for a recombinant FSH dosage normogram.

BACKGROUND: The aim was to identify independent predictors of ovarian response to recombinant (r)FSH through a multiple regression analysis. METHODS: Prospective study including 145 'standard' patients treated with 150 IU/day of rFSH during their first IVF/ICSI cycle. Down-regulation was achieved with long agonist protocol. The following were examined as possible predictive factors: age, body mass index, cycle length, smoking status and on day 2-5: total ovarian volume, total number of antral follicles (<10 mm), total Doppler score of the ovarian stromal blood flow, serum FSH, LH, estradiol, inhibin B, and testosterone. RESULTS: Total number of antral follicles, total Doppler score, serum FSH, LH, estradiol, inhibin B, smoking status and cycle length were independent predictors of the number of aspirated follicles. The number of oocytes was predicted by the total number of antral follicles, total Doppler score, serum testosterone and smoking status. In bivariate linear regression analyses ovarian volume was a highly significant predictor of both the number of follicles (P < 0.001) and the number of oocytes (P < 0.001). CONCLUSIONS: Among 12 investigated possible predictive factors in 'standard' patients, the total number of antral follicles and ovarian stromal blood flow assessed by total Power Doppler score are the two most significant predictors of ovarian response. Suggestion for an rFSH dosage normogram is presented.

Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial.

BACKGROUND: The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF. METHODS: Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used. All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test. The study group (n = 150) withdrew vaginal progesterone from the day of positive HCG. The control group (n = 153) continued administration of vaginal progesterone during the next 3 weeks of pregnancy. RESULTS: The number of miscarriages prior to and after week 7 of gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and 13 (8.5%) in the control group respectively. The number of deliveries was 118 (78.7 %) in the study group and 126 (82.4 %) in the control group. The differences were not significant. CONCLUSIONS: Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate, and thus no effect on the delivery rate. Progesterone supplementation can safely be withdrawn at the time of a positive HCG test.

Hydrosalpinx and IVF outcome: cumulative results after salpingectomy in a randomized controlled trial.

BACKGROUND: A randomized controlled trial of salpingectomy prior to IVF in patients with hydrosalpinges has been conducted in Scandinavia. The results from the first transfer cycle have been published and clearly demonstrated an improved pregnancy outcome after salpingectomy had been performed in patients with hydrosalpinges large enough to be visible on ultrasound. The present article is aimed at analysing the effect of salpingectomy on cumulative birth rate, including all individual transfer cycles. METHODS AND RESULTS: A total of 186 women underwent 452 cycles. Among the 77 women randomized to no surgical intervention, 24 underwent salpingectomy after one or two failed cycles. Cumulative results were analysed by Cox regression, taking into account the number of cycles per patient and the presence of a salpingectomy after a previous transfer. Salpingectomy implied a significant increase in birth rate (hazard ratio 2.1, 95% CI 1.6-3.6, P = 0.014). Within the subgroup of patients with ultrasound-visible hydrosalpinges, the birth rate was even higher (hazard ratio 3.8, 95% CI 1.5-9.2, P = 0.004). Implantation rate was significantly higher in patients who had undergone salpingectomy (27.2% versus 20.2, P = 0.03) and, in the subgroup of patients with ultrasound-visible hydrosalpinges, the difference was even larger (30.3% versus 17.1%, P = 0.003). CONCLUSIONS: The results of the cumulative cycles strengthen the recommendation for a laparoscopic salpingectomy prior to IVF in patients with ultrasound-visible hydrosalpinges.

Prophylactic salpingectomy does not impair the ovarian response in IVF treatment.

To examine the effect of prophylactic salpingectomy in patients with hydrosalpinges on the ovarian response to stimulation prior to IVF, 26 patients were included in a study in which they acted as their own controls. They were all part of a randomized controlled study, in which they had been randomized to no surgical intervention prior to IVF. After one or two failed cycles, they underwent laparoscopic uni- or bilateral salpingectomy of their diseased tubes. The cycles before and after surgery were compared and the ovarian response was assessed as the dose and duration of gonadotrophins and the number of retrieved and fertilized oocytes. There were no significant differences in any of the measured outcomes. The increasing age between cycles did not influence the ovarian response, assessed by a comparison with two matched control groups from the same original study; 46 patients salpingectomized before IVF and 25 patients without surgery. It is concluded that removal of hydrosalpinx as a prophylactic laparoscopic procedure does not compromise ovarian function.

Progesterone supplementation during early gestation after in vitro fertilization has no effect on the delivery rate.

OBJECTIVE: To compare the delivery rate with IVF or ICSI in women who did and did not receive progesterone supplementation in the first 3 weeks after a positive hCG test result. DESIGN: Retrospective study. SETTING: Fertility Clinic, Rigshospitalet University Hospital, Copenhagen, Denmark. PATIENT(S): 200 pregnant women who did not receive progesterone (intervention group) and 200 pregnant women who received progesterone for 3 weeks after a positive hCG result. INTERVENTION(S): In the study group, vaginal progesterone therapy was withdrawn on the day of positive hCG result. In the control group, treatment with progesterone, 600 mg/d, was continued for 3 weeks after a positive hCG result. Both groups received 600 mg of progesterone starting on the day of embryo replacement until testing positive for pregnancy 14 days after embryo transfer. MAIN OUTCOME MEASURES: Delivery rate. RESULT(S): The number of deliveries was 126 in the study group and 128 in the control group. CONCLUSION(S): The delivery rate was the same in pregnant women who received and those who did not receive progesterone for 3 weeks after a positive hCG result. Progesterone supplementation for more than 2 weeks after embryo transfer may therefore yield no benefit in terms of pregnancy.

Hydrosalpinx and ART. Salpingectomy prior to IVF can be recommended to a well-defined subgroup of patients.

The result of the Scandinavian multicentre study on salpingectomy prior to IVF has promoted a discussion on whether there is a risk of unnecessary salpingectomies being performed. We agree that physicians have to discriminate carefully between a hydrosalpinx that should be removed and one that is suitable for surgical repair. Tubal endoscopy is the most advanced tool for that purpose, while transvaginal ultrasound is not appropriate in selecting patients to undergo either salpingectomy or salpingostomy. The Scandinavian study showed that patients with hydrosalpinges which are large enough to be visible on ultrasound before ovarian stimulation, benefit from salpingectomy in terms of improved fertility outcome after IVF. The result of the study does not interfere with the management of distal tubal infertility in general, since it was concluded that not every woman with a large hydrosalpinx should undergo salpingectomy. Hydrosalpinges with preserved mucosa may be better treated with reconstructive surgery as primary treatment instead of salpingectomy and IVF. The latter option may, however, be the secondary treatment after failed conception and re-occlusion of the tubes. Unnecessary salpingectomies should, of course, not be performed and they may easily be avoided by appropriate evaluation of the tubal mucosa at laparoscopy before any final decision of salpingectomy is made. We do not see a major conflict: functional surgery to the tubes with healthy mucosa and salpingectomy to the dilated tubes that are visible on ultrasound and have a severely damaged mucosa.

[Infertility in ethnic groups. Etiology and treatment]. / Infertilitet hos etniske par. Arsager og behandling.

In this retrospective case control study we analysed the causes and treatments of infertility in 100 ethnic couples consecutively discharged from the Fertility Clinic in the period October 1995 to March 1999. The mean age at referral was 28 years (19-37) for ethnic women and 31 years (24-39) for Danish women. Male infertility was the most frequent cause in ethnic couples compared to Danish couples (24% vs. 16%; NS). Tubal infertility was less frequent in ethnic than in Danish couples (19% vs. 45%; p < 0.01), ovulatory defects were more frequent in ethnic couples than in Danish (13% vs. 4%; p < 0.04). Among ethnic couples 57 (118 cycles) underwent IVF and ICSI treatment vs. 85 (198 cycles) Danish couples (p < 0.01). The ongoing pregnancy rate per initiated cycle was 29.6% in ethnic couples vs. 24.2% in Danish couples (NS). Forty four percent of the ethnic couples did not complete the whole treatment program vs. 29% of Danish couples (p < 0.04). This may be due to cultural differences and difficult communication.

Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF.

Many retrospective studies have shown that hydrosalpinx is associated with poor in-vitro fertilization (IVF) outcome. The mechanism of the actual cause is not yet fully understood. A clinical practice of performing salpingectomy before IVF has developed, without any evidence from prospective trials. The aim of the present prospective randomized trial was to test if a salpingectomy prior to IVF was effective in terms of increased pregnancy rates. Patients with hydrosalpinx were randomized to either a laparoscopic salpingectomy or no intervention before IVF. A total of 204 patients was available for an intention-to-treat analysis and 192 actually started IVF. Clinical pregnancy rates per included patient were 36.6% in the salpingectomy group and 23.9% in the non-intervention group (not significant, P = 0.067) and the ensuing delivery rates were 28.6% and 16.3% (P = 0.045). The corresponding delivery rates per transfer cycle were 29.5% versus 17. 5% (not significant, P = 0.083). A subgroup analysis revealed significant differences in favour of salpingectomy, in implantation rates in patients with bilateral hydrosalpinges (25.6% versus 12.3%, P = 0.038) and in clinical pregnancy rates (45.7% versus 22.5%, P = 0.029) and delivery rates (40.0% versus 17.5%, P = 0.038) in patients with ultrasound visible hydrosalpinges. The delivery rate was increased 3.5-fold in patients with bilateral hydrosalpinges visible on ultrasound (P = 0.019).

A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994-1997.

This national cohort study included all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) registered in Denmark between January 1994 and July 1997 at five public and eight private fertility clinics. Laboratory and clinical data were obtained from the fertility clinics. The couples answered a questionnaire regarding the pregnancy and the health of the child (response rate 94%). Data validation was carried out through discharge charts. The mean age of the women was 32.1 years. In 84.2% of couples, male factor was the main reason for performing ICSI, and in 4.8% epididymal spermatozoa were used. The mean number of embryos replaced was 2.3 (range 1-3) and in 95% of cases fresh embryos were transferred. Only 183 women (28.5%) underwent prenatal diagnosis, resulting in 209 karyotypes with seven (3.3%) chromosome aberrations. Six major chromosomal abnormalities (2.9%) and one inherited structural chromosome aberration (0.5%) were found, but no sex chromosome aberrations. The frequency of multiple birth, Caesarean section rate, gestational age, preterm birth, and birth weight were comparable with previous studies. The perinatal mortality rate was 13.7 per 1000 children born with a gestational age of 24 weeks or more. In 2.2% (n = 16) of the liveborn infants, and in 2.7% (n = 20) of all infants, major birth defects were reported by the parents. Minor birth defects were found in nine liveborn infants (1.2%). In conclusion, the results of this study on outcome of ICSI pregnancies are in line with earlier reports, except that no sex chromosome abnormalities were found.

Delivery rates after in-vitro fertilization following bilateral salpingectomy due to hydrosalpinges: a case control study.

This retrospective case-control study assessed the impact of bilateral salpingectomy due to uni- or bilateral hydrosalpinges on the outcome of in-vitro fertilization (IVF) in a large consecutive series of patients. The effect of bilateral salpingectomy due to hydrosalpinges on pregnancy outcome was compared in 139 patients (263 cycles) and 139 age-matched controls with tubal infertility without hydrosalpinges (296 cycles). The delivery rates per initiated cycle as well as the implantation rates were equal in the two groups (21.7 versus 21.6% and 19 versus 21%). The number of embryos, the cleavage stage, and the embryo morphology score were equal in the two groups. Among 92 patients treated with 182 IVF cycles who underwent salpingectomy between 1.5 and 5 years prior to their first IVF cycle, the delivery and the implantation rates were 22.5 and 20.5% respectively. Of the patients with salpingectomy after an average of 1.7 failed IVF cycles and who re-entered the IVF programme 3 and 6 months subsequent to surgery, 47 were treated with 83 IVF cycles. The live birth and the implantation rates after surgery in this group were 20.5 and 20% respectively. It is concluded that bilateral salpingectomy due to hydrosalpinges restores a normal delivery as well as implantation rate after IVF treatment compared to controls. A favourable outcome is also found in patients operated on after repeated IVF failures. Furthermore, a normal live birth rate as well as a high implantation rate is maintained for at least three IVF cycles subsequent to surgical treatment.

Pregnancy after assisted ejaculation procedures in men with spinal cord injury.

OBJECTIVE: To present the results of fertility treatment in 28 men with spinal cord injury (SCI) and their partners. DESIGN: Retrospective analysis. SETTING: University hospital outpatient clinic and home. PATIENTS: Twenty-eight anejaculatory men with SCI and their partners seeking treatment for infertility. INTERVENTION: Penile vibratory stimulation and electroejaculation as semen retrieval methods. Assisted reproductive techniques used: vaginal self-insemination at home, intrauterine insemination, in vitro fertilization with or without intracytoplasmic sperm injection. MAIN OUTCOME MEASURES: Ejaculation rate; sperm count and motility; pregnancy rates. RESULTS: All of the men were able to ejaculate either by penile vibratory stimulation (79%) or electroejaculation (21%). Median total sperm count was 65 million (range, 0.1 to 480) with a median motility of 13% (range, 1% to 60%). Overall, 9 of 28 couples (32%) achieved 10 pregnancies (4 self-insemination, 3 intrauterine insemination, 1 in vitro fertilization, and 2 intracytoplasmic sperm injection). CONCLUSIONS: An ejaculation rate of 100% was achieved using penile vibratory stimulation as a first treatment option with electroejaculation as a second option. Motivated couples with adequate semen quality may be offered penile vibratory stimulation combined with self-insemination at home. Together with intrauterine insemination or fertilization techniques used in vitro, the pregnancy rate per treatment cycle for SCI couples may approach that of natural procreation in healthy and fertile couples.

Surgical management of tubal infertility. A regional study.

OBJECTIVE: To investigate an unselected group of patients in a regional area undergoing tubal surgery for infertility and to identify those women who would benefit from surgery and those who should be referred directly to in vitro fertilization (IVF). DESIGN: A retrospective study based on medical records and questionnaires. SETTING: The Departments of Obstetrics and Gynecology, Gentofte. Glostrup and Herlev Hospitals, University of Copenhagen, Denmark. SUBJECTS: Two hundred and thirty-six women with primary or secondary infertility undergoing tubal surgery or adhesiolysis during a five year period from 1985 to 1989 with a follow-up period of minimum of 24 months. RESULTS: Ninety-four women (40%) became pregnant at least once and accounted for the total number of 144 pregnancies. One hundred and forty-two patients (60%) did not become pregnant. The delivery rate was 25%, and 37 women (16%) had at least one ectopic pregnancy. There were no significant differences in the delivery rates of the operations in between, but the risk of ectopic pregnancy was significantly lower after adhesiolysis only than after tubal surgery (p < 0.05). The initial laparoscopic findings could not be used to predict the probability of intrauterine pregnancy. CONCLUSION: There is still a place for surgical treatment of tubal infertility, but the risk of ectopic pregnancy should be taken into account before a decision concening line of treatment is made.

[The postmenopausal ovary--should it be preserved?]. / Det postmenopausale ovarium--bør det bevares?

Oophorectomia per occasionem is often performed in connection with hysterectomy in peri- and postmenopausal women as prophylaxis against ovarian cancer. Reviewing published articles has shed little light on whether the postmenopausal ovaries have an endocrine function, and whether such a function may have physiological importance. Population studies of healthy women, comparisons of oophorectomized and non-oophorectomized postmenopausal women and measurements of ovarian venous gradients have shown that the postmenopausal ovaries contribute substantially to the production of androgens, and produce about half the body's circulating testosterone. In a number of women there is a continued significant oestrogen production in the ovaries during the first five to ten years following menopause. After this period the ovarian contribution to the total oestrogen production is very small. To what extent the continued androgen production could have physiological importance cannot be decided by reviewing the literature. Androgens seem to have importance for sexual function, but could possibly also have negative effects in the form of an increased risk of cardiovascular disease. We lack both epidemiological investigations and in-vitro perfusion studies of human ovaries in order to illuminate the physiological function of the postmenopausal ovary. In deciding on oophorectomia per occasionem in the postmenopausal woman the possible advantages of continued ovarian hormonal production must be weighed against the risk of later development of ovarian cancer, which is 2%, identical to that of the risk in the background population.

[Evaluation of home pregnancy tests]. / Vurdering af graviditetstest til hjemmebrug.

Three home pregnancy tests, Clearblue (Tjellesen), Clearblue one step (Tjellesen) and Predictor (Organon), were tested and compared with respect to sensitivity, specificity, prozone-phenomenon and convenience for use. In addition, they were compared with two well-known pregnancy tests, HCG-Novoclone (Novo) and HCG-Nostick (Organon), which are used in several hospitals and drugstores. All three home pregnancy tests were found to be in agreement with the instructions for use with regard to sensitivity and prozone phenomenon. One test, Clearblue one step, showed false positive results when LH was added. Clearblue was found to be laborious and unhygienic in performance. Predictor seems to be the test of choice.

Postmortem findings and prenatal diagnosis of Zellweger syndrome. Case report.

The postmortem findings of siderosis, renal cortical cysts, pachygyria, cortical heterotopia of the brain and cerebellar hypoplasia in a seven-week-old infant with craniofacial dysmorphism and hypotonia prompted the diagnosis of Zellweger syndrome. This was confirmed by analysis of very-long-chain fatty acids in blood spots from filter paper, collected in the neonatal period, and allowed first trimester diagnosis in the subsequent pregnancies.

Frequency of curettage in middle-aged women treated with sequential preparations versus untreated women.

Over a 2-month period a register was kept of all dilatation and curettage procedures performed in Frederiksborg County, Denmark, involving women aged 40-59 years. The total recorded was 284. In the same period, questionnaires were sent out to 1200 women in the county who fell within the same, randomly selected age group, to establish the number of women treated with sequential oestrogen/progestogen and those who had been hysterectomized. Based on the results and the total female population in the county, it was calculated that the frequency of the procedure in sequentially-treated women as compared with untreated women was 3.1 times higher in the 55-59 age group. In the 40-54 age group no difference in the incidence of curettage in the sequentially-treated women could be demonstrated.