Serum estradiol as an aid in the diagnosis of ectopic pregnancy.

The value of serum beta-hCG measurement in the diagnosis of ectopic pregnancy is well established, and there have been recent studies on the use of serum progesterone levels. However, we have been unable to find any reports on the potential application of serum estradiol (E2) assays in the diagnosis of ectopic pregnancy. We therefore concurrently measured serum E2, progesterone, and beta-hCG in 100 women with ectopic pregnancies, as well as in 69 controls with normal intrauterine pregnancies and 36 women with threatened abortion. The mean (+/- standard deviation) E2 levels for ectopic-pregnancy patients, the normal controls, and the women with threatened abortion were 281.1 +/- 115.6, 788.2 +/- 45.5, and 788.8 +/- 40.6 pg/mL, respectively; the mean levels in the ectopic group were significantly different (P less than .0001) from those of the other two groups. All but one of the ectopic pregnancies had values below 650 pg/mL for E2 and 23 ng/mL for progesterone, and all but one of the normal intrauterine pregnancies had values above these levels. Our data suggest that the addition of the estradiol assay, with or without progesterone, to the early evaluation of patients suspected of having an ectopic pregnancy may be helpful in diagnosis.     

Study of serum SP1 levels in early normal and abnormal pregnancies

The pregnancy-specific beta 1 glycoprotein (SP1) levels in the serum of normal and abnormal pregnancies were determined by radioimmunoassay in the first trimester. The results indicated that serum SP1 levels of normal pregnancies increased with the advancing gestational week; 67% of threatened abortions with low SP1 levels would finally abort and only 7% of those with normal SP1 levels would abort. Serum SP1 levels were of lower values in ectopic pregnancy and hydatidiform mole. Serum SP1 might be taken as a better index for estimating the fetal prognosis in threatened abortion and an auxiliary diagnostic means for ectopic pregnancy and hydatidiform mole.     

Diagnosis of ectopic pregnancy: value of the discriminatory human chorionic gonadotropin zone

A prospective study was conducted to test the hypothesis that the absence of an intrauterine gestational sac when the serum level of human chorionic gonadotropin (hCG) is above 6500 mIU/mL is indicative of ectopic pregnancy. A total of 383 patients who were clinically suspected to have ectopic pregnancies had pelvic ultrasound examinations with serum hCG determinations on the day of the scan. There were 217 (57%) intrauterine gestations, 104 (27%) ectopic pregnancies, and 62 (16%) spontaneous abortions. Forty-one percent of patients had an hCG level above 6500 mIU/mL. The absence of an intrauterine gestational sac at an hCG concentration above this level had a sensitivity of 100%, a specificity of 96%, a positive predictive value of 86%, a negative predictive value of 100%, and was 98% efficient, based on a 19.4% prevalence of ectopic pregnancies among this group.     

Maternal serum levels of tumor necrosis factor-alpha and interleukin-2 receptor in threatened abortion: a comparison with normal and pathologic pregnancies

OBJECTIVE: We evaluated tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) receptor levels in patients with threatened abortion and compared the levels with normal and pathologic pregnancies. DESIGN: A prospective, nonrandomized, case-control study. SETTING: Academic research setting. PATIENT(S): Twenty-two patients with threatened abortion, 18 patients with pathologic pregnancies, 20 healthy pregnant women, and 20 nonpregnant women. INTERVENTION(S): Maternal serum TNF-alpha and IL-2 receptor levels were measured with a solid-phase, two-site chemiluminescent enzyme immunometric assay method. MAIN OUTCOME MEASURE(S): TNF-alpha and IL-2 receptor levels. RESULT(S): The mean +/- SEM maternal serum IL-2 receptor level for patients with threatened abortion was 481.3 +/- 35.7 U/mL, compared with 426.5 +/- 22.4 U/mL in the normal pregnant group. There was no statistically significant difference in the mean +/- SEM serum TNF-alpha level between the patients with threatened abortion and those with normal pregnancies (16.1 +/- 2.7 pg/mL vs. 10.9 +/- 0.8 pg/mL). The mean +/- SEM maternal serum IL-2 receptor level was significantly higher in patients with pathologic pregnancies than in those with normal pregnancies (506.2 +/- 27.6 U/mL vs. 426.5 +/- 22.4 U/mL). The mean +/- SEM maternal serum TNF-alpha level was significantly higher in patients with pathologic pregnancies than in those with threatened abortion (39.2 +/- 9.5 pg/mL vs. 16.1 +/- 2.7 pg/mL) and normal pregnancies (39.2 +/- 9.5 pg/mL vs. 10.9 +/- 0.8 pg/mL). CONCLUSION(S): In comparison with normal pregnancies, maternal serum IL-2 receptor and TNF-alpha levels were not significantly increased in patients with threatened abortion with good outcome.     

Maternal serum vascular endothelial growth factor levels in early ectopic and intrauterine pregnancies after in vitro fertilization treatment

OBJECTIVE: To determine whether serum levels of vascular endothelial growth factor (VEGF) 11 days after a day-3 embryo transfer were predictive of outcome, in women with normal intrauterine pregnancy (IUP), first-trimester miscarriage (SAB), biochemical (BC), and ectopic pregnancy (EP) after IVF therapy. DESIGN: Retrospective analysis. SETTING: University hospital IVF unit. PATIENT(S): One hundred eight women who underwent IVF therapy and who were subsequently diagnosed with EP, BC, SAB, or a normal IUP (27 in each category). INTERVENTION(S): Serum samples were obtained at 11 days after a day-3 embryo transfer. MAIN OUTCOME MEASURE(S): Serum concentrations of VEGF, P, and beta-hCG. RESULT(S): Serum concentrations of VEGF were similar in women with BC and EP and higher than in women with normal IUP and SAB (571.8 +/- 61.8, 604.4 +/- 73.4 vs. 448.9 +/- 39.9, 461.8 +/- 39.2 pg/mL, respectively). Also, serum beta-hCG and P levels were significantly higher in women with a normal IUP and SAB. Using a cutoff concentration of >700 pg/mL for VEGF, an EP could be distinguished from an IUP (normal and SAB), with a positive predictive value of 64% and a negative predictive value of 71%. CONCLUSION(S): Elevated maternal serum levels of VEGF, as early as 11 days after embryo transfer, are associated with ectopic pregnancies after IVF.     

Ectopic pregnancy and recurrent spontaneous abortion: two associated reproductive failures

The association between spontaneous abortion and ectopic pregnancy was evaluated in a case-control study conducted on 161 women (cases) with recurrent spontaneous abortions (two or more consecutive spontaneous abortions) and 170 control subjects who delivered normal infants. The risk of ectopic pregnancy in women with a history of recurrent spontaneous abortion was about fourfold that of controls (relative risk adjusted for age and number of pregnancies = 4.3; 95% confidence interval 1.4-14.7). This association was confirmed by comparing the observed number of extrauterine pregnancies in women with recurrent spontaneous abortions with the expected number computed from regional data on the frequency of ectopic pregnancies; the estimated relative risk was 3.7, with a 95% confidence interval of 2.2-7.0. The present report found an association between spontaneous abortions and ectopic pregnancies, suggesting some common risk/etiologic factors for these two reproductive failures.     

Serum interleukin-1β, interleukin-8 and anti-heat shock 60 Chlamydia trachomatis antibodies as markers of ectopic pregnancy

Anti-Chlamydial trachomatis (anti-CT) responses, particularly anti-heat shock 60 (Hsp60), antibodies confer a higher risk of ectopic pregnancy. With emerging evidence supporting the pivotal role of interleukin-1β (IL-1β) and IL-8 in the immunopathogenesis of CT-specific tubal obstruction, we determined anti-CT Hsp60 antibody reactivity and serum concentrations of IL-1β and IL-8 in failed pregnancies consisting of 30 consecutive ectopic pregnancies and 30 missed abortions, with 32 viable intrauterine pregnancies tested as normal controls. ELISAs were utilised to measure IgA or IgG anti-CT major outer membrane outer protein (MOMP) antibodies, IgG anti-CT Hsp60 antibodies and IL-1β and IL-8. IgG anti-CT Hsp60 antibodies were more prevalent in ectopic pregnancy cases (43.3%, 13/30) than in intrauterine pregnancies (16%, 5/32, p=0.016). All 13 ectopic pregnancy anti-CT Hsp60-positive cases had anti-CT MOMP antibodies. CT-specific antibodies were more frequent in merged ectopic pregnancy and missed abortions cases (35%, 21/60) than in intrauterine pregnancies (16%, p=0.049). The median (range) levels of IL-1β in ectopic pregnancy, missed abortions and normal intrauterine pregnancies were 1.74 (0.2-8.7), 1.14 (0.2-16) and 1.22 (0.2-16.2) pg/ml, respectively (p>0.05, for all). Serum IL-8 levels were comparable amongst groups: ectopic pregnancy (median [range]: 25.1 [18.3-1000]); missed abortions (32.9 [15.39-1000]); and intrauterine pregnancies (25.11 [18.3-1000] pg/ml). Anti-CT antibody-positive ectopic pregnancy had significantly lower IL-1β levels (1.29 [0.2-2.93]) pg/ml than sero-negative ectopic pregnancy cases (2.09 [1.10-8.70]) pg/ml, (p=0.022), but IL-8 did not differ. Our data demonstrate that anti-CT Hsp60 immunity is a predominant feature of ectopic pregnancy. We conclude that neither IL-1β nor IL-8 can be considered markers of failed pregnancy, although lower levels of the former cytokine are associated with CT-related ectopic pregnancy.     

Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker?

Objective: To determine serum levels of vascular endothelial growth factor (VEGF) and evaluate their capacity to serve as a marker for the diagnosis of ectopic pregnancy (EP).

Design: Prospective, case-controlled study.

Setting: A tertiary care center.

Patient(s): Twenty women with EP, 10 women with normal intrauterine pregnancy, and 10 women with abnormal intrauterine pregnancy, all at comparable stages of gestation.

Intervention(s): Serum samples were obtained from all women.

Main Outcome Measure(s): All samples were analyzed for VEGF, progesterone, and β-hCG by specific methods.

Result(s): Women with EP had higher serum levels of VEGF than women with normal intrauterine pregnancy and women with abnormal intrauterine pregnancy (median levels, 226.8 pg/mL, 24.4 pg/mL, and 59.4 pg/mL, respectively). With a cutoff level of 200 pg/mL, serum VEGF could distinguish intrauterine from extrauterine pregnancy with a sensitivity of 60%, specificity of 90%, and positive predictive value of 86%.

Conclusion(s): The increased serum VEGF levels in women with EP may facilitate this challenging diagnosis and reduce maternal morbidity and mortality.     

Fetal interleukin-1 receptor antagonist gene polymorphism, intra-amniotic interleukin-1beta levels, and history of spontaneous abortion

OBJECTIVE: The purpose of this study was to determine whether fetal carriage of specific alleles of the polymorphic interleukin-1 receptor antagonist gene is associated with variations in intra-amniotic cytokine levels and previous pregnancy outcomes. STUDY DESIGN: Fetal cells in midtrimester amniotic fluid from 189 women were tested for interleukin-1 receptor antagonist intron 2 length polymorphisms. Concentrations of cytokines in amniotic fluid were tested by enzyme-linked immunosorbent assay. Pregnancy history data were obtained subsequently. RESULTS: Homozygosity for interleukin-1 receptor antagonist allele 1 was detected in 13 of 17 fetuses (76.5%) from women whose previous pregnancies all ended in spontaneous abortions, as compared with 33 of 74 fetuses (44.6%) from women with at least 1 previous term birth ( P = .02). Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with only 1 (5.9%) previous spontaneous abortion, as opposed to 31 pregnancies (41.9%) that were associated with a previous term delivery ( P = .004). A similar relationship between interleukin-1 receptor antagonist allele 1 and spontaneous abortions was observed when pregnancies of white women only were analyzed. Median mid trimester amniotic fluid interleukin-1beta concentrations were higher in women whose previous pregnancies ended in term deliveries (15.7 pg/mL), as opposed to women with 1 to 2 (6.4 pg/mL; P = .04) or > or =3 (4.1 pg/mL; P = .007) previous spontaneous abortions. Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with elevated intra-amniotic interleukin-1beta levels (16.2 pg/mL), as compared with interleukin-1 receptor antagonist allele 1 homozygotes (10.8 pg/mL; P = .03). CONCLUSION: Fetal carriage of interleukin-1 receptor antagonist allele 1 is associated with reduced intra-amniotic interleukin-1beta concentrations and an increased occurrence of spontaneous abortions in previous pregnancies.     

Further observations on serial human chorionic gonadotropin patterns in ectopic pregnancies and spontaneous abortions

The half-life of hCG was measured retrospectively in paired blood samples from 108 pregnancies with falling hCG levels. hCG levels fell significantly more slowly in women who had an ectopic pregnancy (41 cases) than in women who had spontaneous abortions (67 cases). When the hCG half-life was greater than or equal to 7 days, 86% of cases had ectopic pregnancies, a third of which had ruptured. By contrast, when the hCG half-life was less than 1.4 days, only 7.6% (2/26) of cases had an ectopic pregnancy (both of which were unruptured), and villi were identified in only 10% of curettage specimens from (presumed) cases of spontaneous abortion. When the half-life of hCG was between 1.4 and 6.9 days, 34% of the cases had ectopic pregnancies, 14% of which had ruptured: chorionic villi were recovered from 76% of the women who had a curettage, and failure to detect villi was more than 80% predictive of an ectopic pregnancy.     

体外受精-胚胎移植后双次血清β-HCG对妊娠结局的预测价值

目的:探讨体外受精-胚胎移植(IVF/ICSI-ET)后14天及18天双次血清β-人绒毛膜促性腺激素(β-HCG)预测妊娠结局的意义。方法:回顾分析2006年1月至2007年5月在我中心行新鲜周期IVF/ICSI-ET助孕后有14天及18天血清β-HCG水平的1154个周期,并追踪妊娠结局。结果:血清β-HCG水平与妊娠结局相关。移植后14天、18天继续妊娠组血清β-HCG值均高于不良妊娠组(P<0.05);而两组的上升幅度无显著性差异(P>0.05)。多胎组血清β-HCG值高于单胎组(P<0.05);单胎组血清β-HCG值高于流产组(P<0.05);流产组和异位妊娠组的血清β-HCG值均高于生化妊娠组(P<0.05);而流产组血清β-HCG值与异位妊娠组无显著性差异(P>0.05)。有233例患者移植14天抽血检测β-HCG<5IU/L后18天未抽血检测β-HCG,追踪随访有7例患者妊娠,早期流产率为85.71%(6/7),继续妊娠率为14.29%(1/7)。结论:IVF-ET后双次血清β-HCG值对早期妊娠结局有较好的预测价值,有助于临床及早期鉴别诊断。     

Late sequelae of induced abortion in primigravidae. The outcome of the subsequent pregnancies

137 women, who had legal abortions of their 1st pregnancies, were compared with a group of 133 who had spontaneous abortions before the 28th week, and a group of 129 who delivered their 1st pregnancy. The legal abortion group showed 3 ectopic pregnancies, while the other 2 groups showed none. Those who delivered their 1st pregnancy showed the best reproductive function, while the group of spontaneous abortions showed the highest frequency of early abortion. The artificial group showed the highest rate of late spontaneous abortion and premature delivery. There was a decline in the reproductive function of the artificial abortion group in the 3rd and 4th pregnancies, and an increase in the rate of late abortion. This group also showed an increased rate of spontaneous primary and premature rupture of the membranes and a trend toward lower newborn weight. A close correlation was noted between induced abortion before the age of 17 and repeated abortion. A significant correlation was noted between early menarche and legal abortion and also between early menarche and unmarried state in the 1st pregnancy, based on a random series of 250 primagravidae.     

Serial serum human chorionic gonadotropin (hCG) levels in ectopic pregnancy and first trimester miscarriage

Serial serum hCG levels were measured in 50 patients with a tubal ectopic pregnancy and 50 patients with spontaneous miscarriage of an intrauterine pregnancy. Serum samples were obtained at intervals of 3–5 d and more frequently if clinically indicated. The final diagnosis was confirmed by laparoscopy and/or dilatation and curettage. Data were analyzed using a linear regression model. Initial hCG concentrations ranged from 91 to 3,050 mIU/mL. Eighty percent of ectopic pregnancies and 35% of miscarriages were associated with rising hCG concentrations and no significant differences were noted in daily increments of hCG in the two groups (210 ± 30 mIU/mL/day for ectopic pregnancies versus 311 ± 55 mIU/mL/d for miscarriages). Twenty percent of ectopic pregnancies and 65% of miscarriages had falling hCG concentrations and significant differences were noted in the daily decrements of hCG for EP and AB (270 ± 52 mIU/mL/day for ectopic pregnancies versus 578 ± 28 mIU/mL/d for miscarriages (P≤ 0.05). Received: October 1999 / Accepted: 13 December 1999     

白血病抑制因子在早期妊娠、先兆流产及难免流产患者蜕膜组织中表达的研究

目的探讨白血病抑制因子(LIF)在蜕膜组织中的表达,及其与早期妊娠、流产的关系. 方法采用放射免疫方法检测正常早孕妇女(正常早孕组)、先兆流产妇女(先兆流产组)及难免流产妇女(难免流产组)的血清孕酮及人绒毛膜促性腺激素(hCG)水平,并采用逆转录-聚合酶链反应(RT-PCR)技术对3组孕妇蜕膜组织中LIF-mRNA的表达进行定量分析.结果 (1)孕酮及hCG水平在3组孕妇间的比较正常早孕组孕妇血清中孕酮、hCG水平分别为(91.5±27.2) nmol/L、(69.9±14.9) kU/L,先兆流产组孕妇分别为(88.4±24.7) nmol/L、(57.6±11.2) kU/L,两组孕妇血清孕酮、hCG水平比较,差异均无显著性(P>0.05);而难免流产组孕妇血清孕酮、hCG水平分别为(33.1±19.6) nmol/L、(10.3±3.2) kU/L,与前两组分别两两比较,差异均有极显著性(P<0.01).(2)LIF-mRNA平均相对含量在3组孕妇间的比较正常早孕组孕妇为2.10±0.32;先兆流产组孕妇为1.92±0.20;难免流产组孕妇为0.70±0.06.正常早孕组与先兆流产组比较,差异无显著性(P>0.05).而难免流产组与前两组分别行两两比较,差异均有显著性(P<0.05).结论 LIF-mRNA在早期妊娠蜕膜组织中的表达量降低,可能是导致hCG及孕酮分泌下降,最终造成难免流产的原因之一.     

Ectopic pregnancy concurrent with induced abortion: incidence and mortality

From 1972 through 1985, 24 women who underwent an induced abortion died as a result of a concurrent ectopic pregnancy. We analyzed data from the Joint Program for the Study of Abortion, National Hospital Discharge Survey, and the Centers for Disease Control Ectopic Pregnancy and Abortion Surveillance Systems to determine the incidence and mortality of ectopic pregnancy concurrent with induced abortion. During the period 1971 through 1985, the incidence of ectopic pregnancy concurrent with induced abortions was 1.35/1000 induced abortions, compared with 13.6/1000 pregnancies not terminated by induced or spontaneous abortion. The rate was higher among women who obtained abortions at earlier gestational age and among older women. The death-to-case rate for ectopic pregnancies concurrent with induced abortion was 1.3 times higher than that for women not undergoing abortion. Most of the deaths of women with ectopic pregnancy who underwent induced abortion were attributable to the failure to diagnose the ectopic pregnancy before the woman left the facility where the abortion was performed. Such deaths could be prevented by the provider of the abortion assuring that the tissue is examined for products of conception at the time of the abortion.     

Spontaneous abortion--an infectious aetiology?

The role of Chlamydia trachomatis, genital mycoplasmas, Campylobacter spp. and other aerobic and anaerobic bacteria in the aetiology of spontaneous abortion was investigated prospectively in 241 pregnant women at a community hospital. Sixteen women who had threatened abortions were a little younger, of lower social class and had had more previous spontaneous abortions than the 76 women who aborted or the 149 women whose pregnancies were not complicated in the early stages by haemorrhage. The demographic characteristics of the latter two groups of women were similar. C. trachomatis was isolated from the cervix of only one woman and she had no genital-tract bleeding at any stage in her pregnancy. Mycoplasma hominis was isolated most often from the women who had threatened abortions but otherwise the prevalence of the other various micro-organisms was similar in women who had spontaneous abortions, threatened abortions, and in those who had pregnancies uncomplicated by vaginal bleeding. It was clear, therefore, that C. trachomatis played no role in the aetiology of spontaneous abortion in the population studied and there was no suggestion that any of the other micro-organisms were involved either.     

Spontaneous abortion-an infectious aetiology?

Summary. The role of Chlamydia trachomatis , genital mycoplasmas, Campylobacter spp. and other aerobic and anaerobic bacteria in the aetiology of spontaneous abortion was investigated prospectively in 241 pregnant women at a community hospital. Sixteen women who had threatened abortions were a little younger, of lower social class and had had more previous spontaneous abortions than the 76 women who aborted or the 149 women whose pregnancies were not complicated in the early stages by haemorrhage. The demographic characteristics of the latter two groups of women were similar. C.trachomatis was isolated from the cervix of only one woman and she had no genital-tract bleeding at any stage in her pregnancy. Mycoplasma hominis was isolated most often from the women who had threatened abortions but otherwise the prevalence of the other various micro-organisms was similar in women who had spontaneous abortions, threatened abortions, and in those who had pregnancies uncomplicated by vaginal bleeding. It was clear, therefore, that C.trachomatis played no role in the aetiology of spontaneous abortion in the population studied and there was no suggestion that any of the other micro-organisms were involved either.     

Serum concentrations of interleukin-2R (IL-2R), IL-6, IL-8, and tumor necrosis factor alpha in patients with ectopic pregnancy

OBJECTIVE: To investigate the diagnostic relevance of serum cytokine concentrations in ectopic pregnancy (EP). DESIGN: Cohort study. SETTING: University hospital. PATIENT(S): Seventeen women with EP, 22 women with miscarriage, and 33 women with normal intrauterine pregnancy, at comparable stages of gestation. INTERVENTION(S): Interleukin (IL)-2 receptor, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) determination by immunoradiometric assay. MAIN OUTCOME MEASURE(S): Serum concentrations of progesterone, beta-hCG, IL-2R, IL-6, IL-8, and TNF-alpha. RESULT(S): Serum levels of IL-6 were higher in women with EP than in those with miscarriage and normal pregnancy. Serum levels of TNF-alpha were higher in women with EP than in those with miscarriage and normal pregnancy. Serum levels of IL-8 were higher in women with EP than in those with miscarriage and normal pregnancy. An IL-8 cutoff of >40 pg/mL predicted EP with a sensitivity of 82.4%, a specificity of 81.8%, and positive and negative predictive values of 58.3% and 93.8%. No difference in serum IL-2R levels was found among the groups. CONCLUSION(S): Serum IL-8, IL-6, and TNF-alpha concentrations are higher in women with EP than in those with miscarriage and normal pregnancy. Further studies are needed to determine their diagnostic value.     

Serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies

A prospective study was initiated to closely examine maternal serum concentrations of CA-125 during the early first trimester of normal and abnormal pregnancies. Sequential serum specimens were obtained from 43 women with a normal intrauterine pregnancy, 20 with a surgically confirmed ectopic gestation and 10 whose pregnancies ended in spontaneous abortion. In normal pregnancies the CA-125 levels increased significantly from the first week after the missed menses (39.9 +/- 8.2 U/mL [mean +/- SEM]) to the second week (48.3 +/- 6.9 U/mL) (P less than .05) and from the second to the third week (62.5 +/- 9.8) (P less than .05). After the third week after the missed menses the mean CA-125 serum concentrations plateaued, but levels observed during the fourth (59.6 +/- 8.8 U/mL) and fifth (48.8 +/- 7.2 U/mL) weeks were still significantly greater than at week 1. In addition, the mean CA-125 concentrations were significantly higher in normal pregnancies than in ectopic gestations during the second, third and fourth weeks after the missed menses. Although there was a tendency for the CA-125 levels to be lower in women who had a spontaneous abortion when compared to normals, these differences were not statistically significant. Serum levels of CA-125 may prove useful in monitoring early pregnancy.     

Factors affecting fetal loss in induction of ovulation with gonadotropins: increased abortion rates related to hormonal profiles in conceptual cycles

Thirty-six first-trimester abortions (9.7%), 16 second-trimester abortions (4.3%), 11 ectopic pregnancies (2.9%), and 10 stillbirths (2.7%) occurred in 373 conceptual cycles after gonadotropin induction of ovulation. Fetal wastage was higher in spontaneous pregnancies that occurred before therapy (54.3%, p less than 0.0001) and lower with subsequent spontaneous pregnancies (10.1%, p less than 0.05). Significant risk factors for overall fetal loss during induced ovulation were a continuous rise of estrogen excretion until ovulation (p less than 0.01) and previous abortion (p less than 0.05). For first-trimester abortion, the risk factor was continuous estrogen rise (p less than 0.01); for second-trimester abortion, the risk factors were a low luteal pregnanediol-to-estrogen excretion ratio (p less than 0.002), increased age at conception (p less than 0.02), and high baseline estrogen excretion (p less than 0.05). Multiple pregnancy was not significant. The continuous rising estrogen pattern may serve as a marker of abnormal oocyte maturation. We propose that future studies on infertility treatment should report on pregnancy outcome.