Low-dose aspirin does not improve ovarian responsiveness or pregnancy rate in IVF and ICSI patients: a randomized, placebo-controlled double-blind study.

BACKGROUND: Poor ovarian and endometrial responses to gonadotrophin stimulation in assisted reproduction techniques lead to decreased pregnancy rates. The aim of the present study was to test the hypothesis that low-dose aspirin started prior to controlled ovarian stimulation improves ovarian responsiveness, pregnancy rate (PR) and pregnancy outcome. METHODS: A total of 374 women who were to undergo IVF/ICSI were randomized to receive 100 mg of aspirin (n=186) or placebo (n=188) daily. Treatment was started on the first day of controlled ovarian stimulation. It was continued until menstruation or a negative pregnancy test. Pregnant women continued the medication until delivery. The main outcome measures were the number of oocytes, number and quality of embryos, the clinical PR and pregnancy outcome. RESULTS: The mean (+/-SD) number of oocytes (12.0+/-7.0 versus 12.7+/-7.2), the total mean number of embryos (5.82+/-4.35 versus 5.99+/-4.66), the mean number of top quality embryos (0.99+/-1.39 versus 1.18+/-1.51) and the number of embryos transferred (1.64+/-0.64 versus 1.63+/-0.71) did not differ in the aspirin and placebo groups. Between the aspirin and placebo group, there was no statistically significant difference in clinical PR per embryo transfer (25.3%, n=44 out of 174 versus 27.4%, n=48 out of 175) or clinical PR per cycle initiated (23.7% versus 25.5%). Birth rate per embryo transfer did not differ significantly between the aspirin (18.4%) and placebo (21.1%) groups. The incidence of poor responders [12 (6.5%) versus 13 (6.9%)] was similar in both groups. CONCLUSIONS: The present results indicate that low-dose aspirin treatment does not have any beneficial effect on ovarian responsiveness, PR and pregnancy outcome in unselected women undergoing IVF/ICSI.

Effect of epilepsy and antiepileptic drugs on male reproductive health.

BACKGROUND: Men with epilepsy have reduced fertility, and antiepileptic drugs may affect semen quality. Moreover, animal studies suggest that valproate (VPA) may be associated with testicular atrophy. OBJECTIVE: To evaluate reproductive function in men with epilepsy. METHODS: Sixty men with epilepsy and 41 control men were evaluated for their reproductive health. Fifteen men were taking carbamazepine (CBZ) and 18 men oxcarbazepine (OXC) for partial epilepsy, and 27 men were taking VPA for generalized epilepsy. Reproductive hormones were assayed from serum samples, semen analysis and ultrasonography of the testicles were performed, and testicular volume was calculated. RESULTS: Men on CBZ had low serum dehydroepiandrosterone sulfate concentrations (p < 0.001), and men on VPA had high concentrations of serum androstenedione (p < 0.001). The frequency of morphologically abnormal sperm was higher among CBZ-treated (p < 0.01), OXC-treated (p < 0.05), and VPA-treated men (p < 0.01) than among the control men. Moreover, both CBZ and VPA were associated with poor motility of sperm (p < 0.05). In addition, the frequency of abnormally low sperm concentration was high in men on CBZ (p < 0.001), and the frequency of any sperm abnormality was high in men on VPA (p < 0.01). The VPA-treated men with abnormal sperm had smaller testicular volumes than the control men (p = 0.003). CONCLUSIONS: CBZ, OXC, and VPA are associated with sperm abnormalities in men with epilepsy. In addition, VPA-treated men with generalized epilepsy who have abnormal sperm may have reduced testicular volume.

Maternal serum beta-HCG and alpha-fetoprotein concentrations in singleton pregnancies following assisted reproduction.

BACKGROUND: The reason for the elevated levels of HCG in assisted reproduction pregnancies remains unknown. Our hypothesis was that this increase is caused by the ovarian superovulation therapy. METHODS: We compared the beta-HCG and alpha-fetoprotein (AFP) multiples of the median (MoM) in singleton pregnancies after IVF or ICSI with those achieved by frozen embryo transfer (FET) in spontaneous cycles. RESULTS: The HCG and AFP MoMs (plus minus SEMs) of 59 FET pregnancies were compared with 144 IVF (including 48 ICSI) pregnancies. The maternal HCG of pregnancies following ovarian stimulation was 1.31 plus minus 0.08 MoM compared with 1.35 plus minus 0.12 MoM in the unstimulated ones. The values for AFP were 1.06 plus minus 0.05 versus 1.11 plus minus 0.05 respectively. No significant differences could be observed between pregnancies following stimulated IVF/ICSI and unstimulated FET cycles. CONCLUSIONS: Our results show that second trimester maternal serum HCG is also elevated in singleton pregnancies following spontaneous FET cycles. The increased maternal serum HCG in IVF pregnancies is thus not related to superovulation therapy. Because of the elevated maternal serum HCG levels, serum screening cannot be performed reliably in pregnancies following assisted reproduction technology. Ultrasonographic detection of the nuchal translucency is unaffected and should be used for this group of women undergoing assisted reproduction.

One versus two embryo transfer after IVF and ICSI: a randomized study.

BACKGROUND: The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups. RESULTS: The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS: Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.

Obstetric and perinatal outcome of pregnancies after intrauterine insemination.

The main aim of this study was to evaluate the obstetric and perinatal outcome of pregnancies after intrauterine insemination (IUI) with the partner's spermatozoa combined with ovarian stimulation. Information concerning the antenatal care and obstetric and perinatal outcome of IUI pregnancies (n = 111), spontaneous (n = 333) and in-vitro fertilization (IVF) (n = 333) was obtained from the Finnish Medical Birth Register (MBR). The multiple birth rate in the IUI group was 17% (19/111). Significantly less antenatal care was required by the IUI group than the IVF group. The frequency of Caesarean section was 25% for IUI singletons and 58% for IUI multiples, similar to the other groups. The mean (SD) gestational age for IUI singletons at birth was 39.5 (1.8) weeks, with a mean birth weight of 3285 (575) g, compared with 3448 (600) g in non-assisted singletons (P < 0.05). For IUI multiples the mean gestational age at birth was 36.0 (2.8) weeks and the mean birth weight was 2449 (678) g. The incidence of preterm birth, low birth weight or low Apgar scores and the need for neonatal care were similar in all groups. One case of major malformation and two perinatal deaths were recorded in the IUI group. In conclusion, IUI treatment did not appear to increase obstetric or perinatal risks compared with matched spontaneous or IVF pregnancies. Most problems were associated with patient characteristics and multiple pregnancy. Reduction of the high incidence of multiple pregnancies after assisted reproductive technology is essential to improve its outcome.

Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome.

A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.

Ovarian function during the use of a single contraceptive implant: Implanon compared with Norplant.

OBJECTIVE: To study the mechanism of action of Implanon, a single-rod contraceptive implant containing etonogestrel, in healthy women during 3 years. DESIGN: Prospective, randomized comparison with Norplant. The study was conducted for 2 years in Sweden but was extended to 3 years in Finland. SETTING: Two outpatient clinics. PATIENT(S): Thirty-two healthy women who were between 18 and 40 years of age with normal ovulatory cycles. Seven women receiving Implanon and three receiving Norplant participated in the third year. INTERVENTION(S): On or between days 1 and 5 of a spontaneous menstrual cycle, the subjects received either the etonogestrel-containing implant (Implanon) or the levonorgestrel-containing implant (Norplant). MAIN OUTCOME MEASURE(S): Ultrasonography was performed and/or progesterone concentrations were determined to confirm ovulation in a control cycle. Follicular development, endometrial thickness, and serum concentrations of 17beta-estradiol and progesterone were assessed twice per week during 4-week periods at regular intervals and after implant removal for 6 weeks to monitor return of ovulation. Times required to remove the respective implants were evaluated, as were possible complications. RESULT(S): Seven women who received Implanon and three who received Norplant completed 3 years of study. There were no pregnancies. Ovulation was observed for the first time with Norplant after 18 months. The first ovulation with Implanon was observed after 30 months. Mean endometrial thickness was <4 mm during treatment with Implanon from month 12 onward. The mean (+/-SD) time to remove Implanon was 5.9 +/- 3.4 minutes. The mean (+/-SD) time to remove Norplant was 17.9 +/- 9.9 minutes. Ovulation resumed promptly after the use of either implant. CONCLUSION(S): Results from this study provide convincing evidence of 3-year contraceptive efficacy with Implanon, mainly by ovulation inhibition.

Low pregnancy rate is achieved in patients treated with intracytoplasmic sperm injection due to previous low or failed fertilization in in-vitro fertilization.

The main indications for intracytoplasmic sperm injection (ICSI) are severe male factor and fertilization failure or a low fertilization rate in previous in-vitro fertilization (IVF) treatments. The fertilization and pregnancy rates after ICSI, however, are seldom reported separately for these two different indications. The aim of this study was to compare the treatment outcome and pregnancy rate after ICSI between 65 patients with previous failed fertilization or a low fertilization rate without male factor, and 219 patients with a primary male factor. From the 2726 oocytes collected, 2087 (77%) were micro-injected and 1355 (65%) achieved normal fertilization. The oocyte fertilization rate was similar in the group with previous failed fertilization or a low fertilization rate and the group with a male factor (65 and 65% respectively), as was the cleavage rate of normally fertilized oocytes (92 and 94% respectively). Despite the similar fertilization and cleavage rates and the similar number and morphological quality of embryos transferred in both groups, the pregnancy rate was significantly lower (P < 0.05) in the group with previous failed fertilization or a low fertilization rate than in the group with a male factor (19.6 versus 33.5% respectively; 95% confidence intervals for the difference, 2-26%). The implantation rate was also lower (P = 0.01) in patients with previous failed fertilization or a low fertilization rate (9.6%) than in the group with a male factor (19.5%). We conclude that patients with previous failed fertilization or a low fertilization rate in standard IVF without male factor have a significantly smaller chance of becoming pregnant after subsequent ICSI than patients with a primary male factor. This poor outcome probably reflects intrinsic oocyte defects not bypassed by ICSI.

Long gonadotrophin releasing hormone agonist/human menopausal gonadotrophin protocol for ovarian stimulation in intrauterine insemination treatment.

OBJECTIVE: This prospective study was undertaken to examine the usefulness of a long gonadotrophin releasing hormone agonist (GnRH-a)/human menopausal gonadotrophin (hMG) protocol in intrauterine insemination (IUI) treatment. The results were compared to those of clomiphene citrate (CC)/hMG/IUI. STUDY DESIGN: Seventy-five patients were recruited to a GnRH-a/hMG group (group 1) while 88 patients underwent CC/hMG stimulation and served as controls (group 2). The study subjects were stimulated with a long GnRH-a/hMG regimen. IUI was performed 36 h after the administration of human chorionic gonadotrophin. RESULTS: The number of preovulatory follicles, the thickness of endometrium and sperm parameters were similar in both groups. The hMG requirements were significantly higher in group 1 than in group 2 (21.2 +/- 5.1 vs. 8.1 +/- 3.1 ampoules). The pregnancy rate was 20% in group 1 and 12.5% in group 2, the difference being not significant. CONCLUSION: The pregnancy rates were not significantly different between the GnRH-a/hMG/ IUI and CC/hMG/IUI groups. In addition, GnRH-a/hMG stimulation is notably more expensive than CC/hMG, and for these reasons, GnRH-a/hMG stimulation is not cost-effective in routine IUI therapy.

Comparison of fallopian tube sperm perfusion with intrauterine insemination in the treatment of infertility.

OBJECTIVE: To compare the efficacy of fallopian tube sperm perfusion utilizing a Foley catheter technique with standard IUI. DESIGN: Randomized controlled study. SETTING: The infertility units of the University Central Hospital and the Family Federation of Finland, Oulu, Finland. PATIENT(S): One hundred infertile women with unexplained factor, minimal to mild endometriosis, mild male factor, or ovarian dysfunction, undergoing 50 IUI and 50 fallopian tube sperm perfusion cycles stimulated by clomiphene citrate and hMG. INTERVENTION(S): Thirty-six hours after hCG administration, patients were randomized to either the IUI group (group 1, 50 patients and cycles) or the fallopian tube sperm perfusion group (group 2, 50 patients and cycles). Intrauterine insemination was performed using a standard method and fallopian tube sperm perfusion with a pediatric Foley catheter, which prevents the reflux of sperm suspension. MAIN OUTCOME MEASURE(S): Number of clinical pregnancies. RESULTS(S): The fallopian tube sperm perfusion method using a Foley catheter technique was easy to perform and convenient for the patients. The overall pregnancy rate per cycle was 8% for fallopian tube sperm perfusion and 20% for IUI, a difference that was not significant. CONCLUSION(S): The fallopian tube sperm perfusion method using a Foley catheter offers no advantage in comparison with the conventional IUI technique.

Intrafollicular insemination for the treatment of infertility.

The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertility was investigated in a pilot study. A total of 50 infertility patients with normal tubal function verified by laparoscopy or hysterosalpingography were stimulated with clomiphene citrate/human menopausal gonadotrophin. Washed spermatozoa were injected into one to three pre-ovulatory follicles via vaginal puncture 12 or 30 h after human chorionic gonadotrophin administration. Natural progesterone was given for luteal support. The IFI procedure was technically very simple and convenient for the patient and no complications were recorded. One normal intra-uterine pregnancy resulted. The results indicate that by comparsion with other assisted reproductive technologies IFI is very inefficacious for treating non-tubal infertility. Our data suggest that the intrafollicular environment in the preovulatory period is not favourable for fertilization.

Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study.

One-hundred women undergoing ovarian stimulation with gonadotrophin-releasing hormone agonist (GnRH-a) and a human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF) participated in this randomized comparative study. The effectiveness of long-acting s.c. goserelin (Zoladex depot; 49 patients) and intranasally (i.n.) administered buserelin acetate (Suprefact; 51 patients) for pituitary down-regulation was compared. Treatment with s.c. goserelin (3.6 mg) or i.n. buserelin acetate (200 micrograms; 6 times/day) was started on day 21-23 of the cycle. Stimulation with 150 IU of HMG/day was started after at least 11 days of GnRH-a treatment. There were no differences in the time required for follicular development nor in the clinical outcome between groups treated with either goserelin or buserelin. The number of oocytes recovered in the goserelin group was 6.7 +/- 5.0 versus 6.3 +/- 4.9 in the buserelin group. There were 11 pregnancies after the use of goserelin (22.4%) and 12 pregnancies in those given buserelin (24.0%). The number of HMG ampoules needed for follicular maturation was higher in the goserelin group (27.9 +/- 7.8) than in the buserelin group (24.6 +/- 7.8, P < 0.05). The patients given buserelin suffered significantly more from tiredness, depression, headache and abdominal pain than those receiving goserelin, whereas there were no differences between the groups in experiencing mental irritability, nausea and swelling. Subcutaneous goserelin depot injection offers a useful alternative for pituitary down-regulation in IVF stimulation.

Comparison of a local injection of hyperosmolar glucose solution with salpingostomy for the conservative treatment of tubal pregnancy.

OBJECTIVE: To compare a local injection of hyperosmolar glucose and salpingostomy for the laparoscopic treatment of tubal pregnancy in terms of immediate success and postoperative tubal patency. DESIGN: Prospective. PATIENTS, SETTING: Forty women with an unruptured tubal pregnancy were enrolled from among 117 women with ectopic pregnancies (EPs) admitted consecutively to the university clinic. The inclusion criteria were as follows: [1] concentration of beta-hCG in the serum < or = 5,000 IU/L; [2] no living fetus in the EP; and [3] unruptured tubal pregnancy at laparoscopy. INTERVENTIONS: After randomization, 20 of these patients were treated with a local injection of hyperosmolar (50%) glucose solution and 20 women by salpingostomy. Tubal patency was evaluated at relaparoscopy or by hysterosalpingography 6 to 13 months after the primary treatment. RESULTS: The mean decrease in beta-hCG concentration from the preoperative value to the first postoperative day was 37% and 52% in the glucose and salpingostomy groups, respectively, and the mean resolution time was 13 and 12 days, respectively. Human chorionic gonadotropin showed a persistent EP in 4 women (20%) in the glucose group and 2 (10%) in the salpingostomy group. A patent treated tube was found in 9 of 13 women in the glucose group and 9 of 10 in the salpingostomy group at re-examination. During a follow-up of 6 to 20 months 4 women in the glucose group and 4 women in the salpingostomy group had an intrauterine pregnancy. CONCLUSION: A local injection of hyperosmolar glucose is a reasonable method treating tubal pregnancy in selected cases but does not seem to offer any advantage over salpingostomy concerning persistent trophoblastic disease rate.

Ectopic pregnancy and infertility following treatment of infertile couples: a follow-up of 929 cases.

A follow-up analysis was made of 929 infertile couples, with special attention paid to ectopic pregnancy. The conception rate was 46%, and 9% of the pregnancies were ectopic. Previous ectopic pregnancy, an industrial occupation and smoking reduced the fecundity and increased the risk of ectopic pregnancy. Tubal damage as a verified reason for infertility and its treatment also increased the risk of ectopic pregnancy. Stepwise logistic regression analysis showed the strongest association with ectopic pregnancy to exist in the case of women with a previous ectopic pregnancy (9.9-fold risk) rather than women with primary infertility. Treatment of tubal damage by salpingostomy entailed a 6.0-fold risk and treatment by other methods a 2.8-fold risk. Women working in industry had a 3.5-fold risk of ectopic pregnancy compared with those in other professions.

Ectopic pregnancy and genital infections: a case-control study.

This case-control study was carried out to evaluate the significance of genital infections as risk factors in ectopic pregnancy. The study population consisted of 86 consecutive patients with ectopic pregnancy and two age- and parity-matched control groups of women with normal early pregnancy; those with planned pregnancy (I; 65 pairs) and those having legal abortion (II; 51 pairs). Histories of salpingo-oophoritis in the two groups (22% against 5%, P less than 0.05), and of cervical Chlamydia trachomatis infection (9% against 0%, P less than 0.05) were more common in patients with ectopic pregnancy than in their controls with planned pregnancy; women in the control group who had undergone legal abortion did not differ from patients with ectopic pregnancy. In serological studies antibodies against Herpes simplex viruses were commoner in patients with ectopic pregnancy than in both control groups (89% against 62%, and 88% against 57%, P less than 0.001). Antibodies against cytomegalovirus were also commoner in patients with ectopic pregnancy than in controls who had had a planned pregnancy (88% against 72%, P less than 0.05). The results support the concept that gynaecological infections are among factors predisposing to ectopic pregnancies.

Radical or conservative surgery for ectopic pregnancy? A follow-up study of fertility of 323 patients.

The fertility of 323 patients desiring pregnancy after operation for ectopic pregnancy was analyzed after a follow-up period of 1 to 11 years (mean 5.1 years). The conception rate was 82%. Full-term delivery was obtained in 79% of the pregnant patients and repeat ectopic pregnancy in 13%. Nulliparous women had a significantly lower (P less than 0.01) conception rate (74%) than parous women (86%). The operation method had no influence on subsequent fertility in women with an intact contralateral tube. The women with intact contralateral tubes had a significantly higher pregnancy (P less than 0.001) and full-term birth (P less than 0.01) rates (87% and 83%, respectively) but significantly lower (P less than 0.001) repeat ectopic pregnancy rate (9%) than the women with affected contralateral tube (51%, 56%, and 52%, respectively). Compared with the parous women (9%), the risk of repeat ectopic pregnancy was significantly (P less than 0.01) higher for nulliparous women (22%). Of the nulliparous women with repeat ectopic pregnancy only 16% had a full-term pregnancy.

Ectopic pregnancy: a case-control study of aetiological risk factors.

Aetiological risk factors for ectopic pregnancies were evaluated in a prospective study of 86 consecutive patients with ectopic pregnancy and two age- and parity-matched control groups of women in normal early pregnancy; those with planned pregnancy (65 pairs) and those having legal abortion (51 pairs). Compared with women with planned pregnancy, the patients with ectopic pregnancy more often had an IUD in situ, they had less frequently used hormonal contraception, and they had more legal abortions, curettages, previous ectopic pregnancies, gynaecological operations and salpingo-oophoritis. Compared with women having legal abortion, the patients with ectopic pregnancy had favoured IUD-usage, or they had been without any contraception, and they had an increased frequency of previous ectopic pregnancies. The frequency of fertility problems was also increased in patients with ectopic pregnancy. Our results show that gynaecological pelvic operations, endometrial curettage and evacuation, gynaecological infections, and usage of IUD are important risk factors for ectopic pregnancy, and that infertility seems to be a sign of this risk. In addition, the clinical characteristics of the patients with ectopic pregnancy were similar to those of the patients having legal abortion.

PIP: Etiological risk factors for ectopic pregnancies were evaluated in a prospective study of 86 consecutive patients with ectopic pregnancy and 2 age- and parity-matched control groups of women in normal early pregnancy; those with planned pregnancy (65 pairs) and those having legal abortion (51 pairs). Compared with women with planned pregnancy, the patients with ectopic pregnancy more often had an IUD im situ, they had used hormonal contraception less frequently, and they had more legal abortions, curettages, previous ectopic pregnancies,gynecological surgery, and salpingo-oophoritis. Compared with women having legal abortion, the patients with ectopic pregnancy had preferred the use of the IUD, or they had been without any contraception, and thus they had an increased frequency of previous ectopic pregnancy. The frequency of fertility problems was also increased in patients with ectopic pregnancy. The authors' results show that gynecological pelvic operations, endometrial curettage and evacuation, gynecological infection, and IUD usage are important risk factors for ectopic pregnancy, and that infertility seems to be a sign of this risk. In addition, the clinical characteristics of the patients with ectopic pregnancy were similar to those of patients undergoing legal abortion.

Ectopic pregnancy--an analysis of the etiology, diagnosis and treatment in 552 cases.

An analysis of the clinical data of 552 patients treated for ectopic pregnancy during 1973-82 in our hospital showed that the prevalence of this complication rose twofold (P less than 0.01) from an annual rate of 10.9 per thousand in 1973 to 20.9 per thousand in 1982. As regards parity distribution, the proportion of the 2-paras increased significantly (P less than 0.05) and this increase was significantly greater (P less than 0.001) than in the total population of parturients during this period. The increasing incidence of ectopic pregnancies had a significant positive correlation (P less than 0.05) with the use of an intrauterine device (IUD), but not with previous or present pelvic inflammatory disease or gynaecological or abdominal surgery. Because the 158 patients with an IUD in situ (34%) had a significantly less frequent past history of salpingitis, pelvic operation, infertility, ectopic pregnancy or spontaneous abortion and had less actual pelvic inflammatory changes than the 259 patients without contraception (57%), the IUD seemed to be directly involved with the increased risk of ectopic pregnancy. In the present study lower abdominal pain occurred in 97% of the patients and menstrual disorders in 93%; pelvic examination revealed adnexal mass in 63% and adnexal tenderness in 90% of the patients. Laparoscopy, a sensitive urinary pregnancy test (detection limit 75 IU/1) and culdocentesis were the most important factors in the diagnosis of ectopic pregnancy as evidenced by positive results in 97, 90 and 83% of the cases, respectively. Due to improved diagnostic procedures the annual rate of an unruptured tube at operation increased from 49% to 73% during the study period.