Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle

We encountered a rare case of combined intrauterine and extrauterine pregnancy that occurred following separate spontaneous ovulations. A 33 year old woman visited our hospital with the chief complaint of abdominal pain on April 16, 1993. Her last menstruation was from March 23 for 6 days. However, the urinary human chorionic gonadotrophin (HCG) on April 19 was 1024 IU/l. Pelvic examination and ultrasonography indicated an extrauterine pregnancy, which was confirmed by laparotomy and histological identification of trophoblast cells. The urinary HCG concentration markedly decreased after the operation. However, the HCG level increased again on the fifth post-operative day, and a gestational sac (11 mm) was identified in the uterine cavity on the 11th post-operative day, indicating that this intrauterine pregnancy was established following spontaneous ovulation which occurred before the removal of the extrauterine pregnancy. This case indicates that a combined pregnancy can occur not only after simultaneous multiple ovulations but also after the separate spontaneous ovulations.     

Diagnostic reliability of vaginal ultrasound in ectopic pregnancy

The therapeutic approach to ectopic pregnancy (EP) has changed over the last decade. A prerequisite for a differentiated management is an early diagnosis of EP. This can be achieved by transvaginal sonography (TVS). The purpose of this study was to evaluate the accuracy of TVS in the diagnosis of EP. 184 patients with clinically suspected ectopic pregnancy were examined by TVS. In 103 cases suspicion of EP was confirmed, in 81 cases it was ruled out. All cases were evaluated by laparoscopy, D&C, serial HCG determinations or sonographic follow-up in case of an intrauterine pregnancy. Sensitivity of TVS in the diagnosis of EP was 96%, specificity 88%, the positive predictive value was 89%, the negative predictive value was 95%. Four cases with a false negative result at TVS were very early in pregnancy and were subjected to laparoscopy because of persistent high HCG values without demonstration of an intrauterine pregnancy. Five cases of sonographically confirmed ectopic pregnancies were missed by the first laparoscopy. These cases required intervention because of clinical symptoms and had low levels of HCG. TVS has a high diagnostic accuracy in the diagnosis of ectopic pregnancy.     

Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility

Methotrexate treatment was compared to laparoscopic salpingotomy for conservative management of ectopic pregnancy in a prospective randomized study. One hundred patients were randomized into two groups using random numbers. Inclusion criteria were an ectopic pregnancy visualized by ultrasound with a pre-therapeutic score <13 as assessed by the following six criteria, graded from 1 to 3: gestational age, human chorionic gonadotrophin (HCG) concentration, progesterone concentration, abdominal pain, haemoperitoneal volume and diameter of the haematosalpinx. The treatments were either 1 mg/kg of methotrexate injected transvaginally into the ectopic pregnancy without anaesthesia or administered i.m. when the pregnancy could not safely or easily be punctured (group 1), or laparoscopic salpingotomy (group 2). Success was defined as the return to normal (<10 mIU/ml) of HCG concentrations. Treatment was successful for 45 of 51 patients in group 1 (88.2%) and 47 of 49 in group 2 (95.9%). Medical treatment was significantly (P < 0.05) associated with shorter postoperative stay (24 compared with 46 h), but HCG returned to normal more quickly after laparoscopic treatment (13 compared with 29 days). Spontaneous reproductive performance was similar in both groups, but overall intrauterine pregnancy was higher, and repeat ectopic pregnancy lower, after methotrexate treatment. In selected cases of ectopic pregnancy, with a pre-therapeutic score <13, methotrexate treatment appeared as safe and efficient as conservative treatment by laparoscopy and was associated with improved subsequent fertility.     

Hormone therapy of spontaneous abortion. Our experience with treatment with Gravibinan

The results of the treatment of 151 pregnancies with threatened and/or habitual abortions by using high hormonal dosages (Gravibinan "Alkaloid") are presented. Eight pregnancies were in primigravidas, the remaining 143 patients having previously had 47 interruptions of pregnancy, 66 deliveries, and 313 spontaneous abortions. Disregarding artificial abortions in 379 previous pregnancies there were 313 or 82.5 per cent spontaneous abortions. The treatment was performed by i. m. applications of Gravibinan, during the first week every two days, during the following two weeks every three days, and until the accomplished 16 weeks of pregnancy every five days. Besides hormonal therapy, all patients were on bed rest; in the following course of pregnancy tocolysis and in the case of opened cervix the cerclage cervicis were performed. The vitality of the ovum and the fetus, as well as the efficacy of the treatment were evaluated by clinical findings, HCG and estriol urinary eliminations, and by ultrasonography. Out of 151 treated pregnancies, 21 (13.91%) resulted in early abotion, 17 (11.26%) in mid-trimester abortion, 6 (3.97%) in pre-term, and 107 (70.86%) in term deliveries. There were two (1.77%) perinatally dead premature infants. HCG urinary eliminations were significantly lower in pregnancies resulting is missed abortion or first-trimenon miscarriage, whereas no difference was established between pregnancies resulting in delivery or mid-trimester abortion. The authors recommend hormonal treatment in early threatening and/or habitual abortions by administering high dosages of estrogens and gestagens. Such a treatment stimulates secretory transformation of the endometrium at the beginning of pregnancy, and this allows early placentation and the uterine growth with a simultaneous quiescence of the myometrium, which, in turn, makes the growth of the ovum possible. The authors stress the importance of a complex procedure in the establishment of the etiology and in the treatment of spontaneous and/or habiutal abortion.     

Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest ('blighted ovum') (n = 9) were studied 16 days after conception, at a time when they were asymptomatic and serum concentrations of beta-human chorionic gonadotrophin (HCG) were in the normal range and increasing at an apparently normal rate. Serum progesterone and oestradiol concentrations were compared with those from normal women matched for gestational age and serum beta-HCG concentration whose singleton intra-uterine pregnancies proceeded normally beyond 20 weeks. Mean serum progesterone concentrations were significantly lower in the women with ectopic pregnancies than in matched controls (P < 0.002); however, there was no difference in the serum progesterone concentrations between women with blighted ova and matched controls. Statistically significant differences were not seen in serum oestradiol concentrations between either group and matched controls. Similarly there was no difference in serum progesterone or oestradiol concentrations in 20 women who conceived ectopic pregnancies and 20 women conceiving blighted ovum pregnancies and their matched intra-uterine controls when conception followed ovarian stimulation. The low serum progesterone concentrations seen in ectopic pregnancy suggest that there is a specific and selective deficiency in progesterone synthesis, which implies that factors other than HCG may influence luteal function.     

Value of chorionic gonadotropin detection in urine samples in the diagnosis of hydatid mole (serologic technic)]

32 patients with hydatid mole were subjected to serological tests to determine the concentration of chorionic gonadotropin (HCG) in the urine. The patients were divided into 2 groups, depending on the duration of the amenorrhea. Group 1 (20 cases) showed a uterus size not exceeding the volume of the 12th week of gestation. Group 2 (12 cases) showed a size corresponding to a more advanced gestational age. In Group 1 the mean concentration of HCG was 123,000 units/liter and in the 2nd, 134,000 units/liter. These results were compared with data obtained from measurement of HCG in normal pregnancies. No significant differences were found between the studied group and the control data. The applicability of urinary HCG measurement for the diagnosis of hydatid mole is considered to be greater in more advanced cases.     

A rapid direct latex agglutination test for HCG (author's transl)

792 urine samples from pregnant patients were investigated by a direct latex agglutination test (LA). Results of this slide test were compared with data derived from a haemagglutination inhibition test (HI). The same results were obtained by both pregnancy tests in 768 (96.7%) out of 792 urine samples. The pregnancy test was negative in 20 cases (2.5%) as assessed by HI, whereas a positive result was recorded with the LA in these cases. Seven were cases of early pregnancy and control tests performed by HI became positive at a later date. The remaining 13 (1.6%) of these patients belonged to a group of pathological pregnancies (missed abortion, threatened abortion, incomplete abortion and ectopic pregnancy). The slide test is more sensitive (1000 I.U. HCG/1 urine) than the HI (1500 I.U.HCG/1 urine). No false positive results were obtained with the LA; false negative results were registered in only 0.5% of cases. A semi-quantitative HCG determination was performed by means of the tube and slide test in 29 urine samples. However, agreement of the data by the two methods was relatively poor, owing to the higher sensitivity of the LA, with consequent inaccurate assessment of HCG excretion. Not much importance need be attached to this finding in view of the diagnostic and prognostic deficiencies of HCG determination. The new slide test was found to be a rapid, simple and accurate pregnancy test.     

Diagnostic ultrasound in threatened abortion and suspected ectopic pregnancy

200 women threatened with abortion during the first 16 weeks of pregnancy were examined with diagnostic ultrasound to determine whether there were signs of intrauterine life. Of the 90 who showed positive signs, 8 aborted spontaneously later, the other 82 continued their pregnancy. The ultrasound investigation revealed no signs of intrauterine life in 110 patients. Of these, spontaneous abortion or later evacuation because of missed abortion 101 (histopathological examination showed degenerated villi in 98), not pregnant 4, mola hydatidosa 3, extrauterine pregnancies 2. An ultrasound examination was performed to ascertain whether 136 women with suspected ectopic pregnancy had intrauterine pregnancies. 61 of them had an intrauterine gestational sac, confirmed at clinical follow-up. One of the 61 was operated on with laparoscopy because of pain; no abnormalities were found. In 36 of the other 75, laparoscopy was performed. Ectopic pregnancy 21, ovarian or parovarian cyst 11, adhesions 2, salpingitis 1, and normal 1. Diagnostic ultrasound is excellent for accurate prognosis in threatened abortion. Unnecessary operations avoided; hospitalization in suspected ectopic pregnancies reduced.     

A prospective study of early pregnancy loss

The New York State Early Pregnancy Detection Study was a prospective study of early pregnancy loss, between implantation and menses, in 217 women attempting to become pregnant during 1989-1992. Women collected urine samples on three consecutive mornings during the late luteal phase of their menstrual cycle, for up to 12 cycles, contributing samples for 1253 menstrual cycles. Urinary human chorionic gonadotrophin (HCG), measured using an immunoradiometric assay, was the biomarker for pregnancy. We observed a range of early pregnancy loss (EPL) rates, from a low estimate of 11.0% to a high estimate of 26.9%, depending on the definition used and the subgroup analysed. Based on a definition of 3 days of HCG concentration > or = 4.00 pmol/l, 2 days > or = 5.33 pmol/l or the last day of HCG > or = 6.67 pmol/l, we identified 115 positive cycles; 95 cycles were clinically confirmed pregnancies and 20 cycles were EPL, giving an EPL rate of 17.4% [95% confidence interval (CI) 11.0-25.6]. In addition, we observed an EPL rate of 19.5% (95% CI 11.3-30.1) for samples collected within a 15 day window around menses, and a rate of 20.3% (95% CI 11.3-32.2) for samples limited to the first three menstrual cycles. Because studies use urine collection schemes other than daily sampling, the definition of pregnancy will be crucial in defining EPL.     

Evaluation of serum inhibin A as a surveillance marker after conservative management of tubal pregnancy

Tubal pregnancy is now commonly managed by laparoscopic salpingostomy or systemic methotrexate. A disadvantage of such conservative management is the need for appropriate follow-up, with serial measurement of serum concentrations of human chorionic gonadotrophin (HCG), to exclude persistent ectopic pregnancy (PEP). Concentrations of inhibin A, also a placental product, are significantly increased during pregnancy and the half-life of inhibin A is significantly shorter than that of HCG. To assess the suitability of inhibin A as a marker of PEP, we studied 16 women who had undergone surgery for a tubal pregnancy, measuring HCG and inhibin during follow-up. The mean +/- SEM time taken to achieve non-pregnant concentrations of inhibin A was significantly shorter than for HCG (4.2 +/- 0.8 days versus 21.6 +/- 4.4 days respectively; P < 0.001 Wilcoxon signed rank test). However, in all women the inhibin A concentration increased rapidly after reaching a nadir, reflecting the return of ovarian function, complicating the interpretation of results. In four women inhibin A was almost undetectable preoperatively, while the corresponding HCG concentration was high. These data suggest that inhibin A will not be a useful marker for PEP but that it may provide a more accurate preoperative assessment of trophoblast viability than HCG, thereby improving management.     

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.     

Treatment of non-extractable common bile duct stones with combination ursodeoxycholic acid plus endoprostheses

To assess the effect of timing of human chorionic gonadotrophin (HCG) administration in ovarian stimulation cycles, the serum oestradiol concentration and follicle profile were compared with the clinical pregnancy rate in 582 ovarian stimulation-intra-uterine insemination (OS-IUI) cycles and 3917 in-vitro fertilization-embryo transfer (IVF-ET) cycles. The pregnancy rates increased exponentially with increasing oestradiol in both OS-IUI and IVF-ET cycles (R2 = 0.720, P < 0.001) but then decreased in OS-IUI cycles when the oestradiol concentration exceeded 5000 pmol/l (R2 = 0.936, P < 0.004) at HCG administration. In OS-IUI cycles the percentages of cycles with three or more mature follicles (> or = 18 mm diameter) increased up to an oestradiol concentration of 5000 pmol/l then declined, mirroring the pregnancy rate (R2 = 0.900, P = 0.01). The exponential increase in pregnancy rate with increasing oestradiol concentration in IVF-ET cycles suggests that high oestradiol concentration does not have a deleterious effect on endometrial receptivity. The decrease in pregnancy rate in OS-IUI cycles when oestradiol concentration exceeded 5000 pmol/l reflected fewer mature follicles, resulting from premature administration of HCG to avoid severe ovarian hyperstimulation syndrome (OHSS). We recommend that HCG administration be delayed until multiple follicles have reached maturity, and reducing the risk of severe OHSS by converting high risk OS-IUI cycles to IVF-ET, or if funds or facilities are unavailable, transvaginally draining all but four or five mature follicles.     

Laparoscopically treated extrauterine pregnancy

During a period of 12 months 55 women were treated for 56 ectopic pregnancies. Forty of the 56 (71%) procedures were performed laparoscopically. The duration of operation was 74 minutes when a conservative procedure was used, and 83 minutes where a salpingectomy was performed. The median duration of a diagnostic laparoscopy followed by laparotomy in 12 women was 83 minutes. Four women (13%) had persistent trophoblast, which necessitated a second operation. Two patients had a second laparoscopy because of lower abdominal pain, but did not need further treatment. Median hospitalization time (including diagnosis and second procedures) for the laparoscopically treated women was three days (range one to 16 days).     

Induction of ovulation in rabbits by pure urinary luteinizing hormone

In 18-week-old nulliparous rabbit does, ovulation was induced with 50 IU of pure urinary luteinizing hormone (LH; LH group), or 50 IU of human chorionic gonadotrophin (HCG; HCG group), in order to determine the effect of these treatments on 17 beta-oestradiol and progesterone concentrations, and on oocyte and embryo quality. Luteinizing follicles, recovered oocytes, progesterone concentration and grade 5 embryos were significantly reduced when pure urinary LH was used. Statistically significant correlations were found: (i) between oestradiol concentration and number of degenerated oocytes in both groups (positive); (ii) between oestradiol concentration and grade 1 and 2 embryos (negative), and grade 5 embryos (positive) in the HCG group; (iii) between progesterone concentration and metaphase II oocytes (negative), and between progesterone and grade 5 embryos (positive), in the HCG group; and (iv) between progesterone and oestradiol concentrations (negative) in the LH group. It seems that the oestradiol to progesterone ratio improves during the early luteal phase when ovulation is induced with LH, and that oestradiol and progesterone concentrations could play a role in determining oocyte and embryo quality.     

Placental isoferritin patterns during normal first trimester and tubal gestations

Placental isoferritin (PLF) has been shown to be involved in the down-regulation of the maternal immune system during pregnancy. In a prospective study, serum PLF concentrations were measured in 33 pregnant women with singleton, normal, ongoing first trimester gestations and compared with those of 22 women with tubal gestations. Diagnoses were based on endocrinological, sonographic, intra-operative and histopathological criteria. Venous blood was obtained from both groups for PLF determination before evacuation of the pregnancy products. beta-Human chorionic gonadotrophin (HCG), 17 beta-oestradiol and progesterone were determined at surgery for the tubal pregnancy patients. The mean +/- SD PLF concentrations were 18 +/- 14, 25.4 +/- 42.3 IU/ml among normal and tubal gestations respectively. Significant differences between normal and tubal pregnancies were found (P < 0.05). Based on PLF measurements, sensitivity (67%) and specificity (33%) values were found to be similar for the normal and ectopic pregnancies. No correlation was found between the other measured pregnancy hormones and PLF for the tubal pregnancy group. Low PLF concentrations among pathological gestations may reflect abnormal trophoblastic activity. The simultaneous assessment of PLF and beta-HCG concentrations which probably originate from different trophoblastic cells, is recommended for better diagnosis and monitoring of first trimester placental activity.     

Endometrial and placental protein markers and ovarian steroids in serum during in-vitro fertilization cycles

The objective of this study was to find the earliest time at which it was possible to detect clinical pregnancy in an in-vitro fertilization (IVF) treatment cycle supported with human chorionic gonadotrophin (HCG), and also retrospectively to diagnose abnormal ovarian- or endometrium-related situations in failure cycles. Serum samples were taken in 41 IVF cycles at frequent intervals from the beginning of ovarian stimulation until menstrual bleeding occurred or a pregnancy was established. Concentrations of oestradiol, progesterone, placental protein 14 (PP14), pregnancy-specific beta 1-glycoprotein (SP1), and pregnancy-associated plasma protein A (PAPP-A) were determined in the serum samples using commercially available (steroid) or purpose-developed (protein) immunoassays. The cycles were retrospectively distributed into four outcome groups: (i) fertilization failure (FF, n = 8); (ii) implantation failure (IF, n = 10); (iii) 'interaction' (embryo-endometrium) cycle (IC, n = 14), and (iv) clinical pregnancy (CP, n = 9). The embryo-endometrium interaction was detected by a rise in SP1 in 23 cycles (70% of embryo transfers) at a time when endogenous HCG was still masked by external support. Early ('false') positive SP1 concentrations were observed in two out of eight and five out of 14 cases in groups FF and IC respectively, but never amongst the ongoing pregnancies (CP). PAPP-A did not distinguish pregnancy from the other outcomes. The PP14/progesterone ratio was lower, later in the cycle, in CP than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transvaginal sonography and human chorionic gonadotrophin measurements in suspected ectopic pregnancy: a detailed analysis of a diagnostic approach

In this prospective study among 208 high-risk patients with suspected ectopic pregnancy, the diagnostic value of transvaginal sonography and serum human chorionic gonadotrophin (HCG) measurements were analysed in detail. The absence of an intra-uterine gestational sac obviously was the most constant sonographic finding among patients with ectopic pregnancy (n = 89), with a very high sensitivity (0.99) but a low specificity (0.41). The application of different HCG cut-off levels improved specificity to 1.00 for values exceeding 4500 IU/l. Clinical utility obviously decreased, as many patients presented with HCG values well below this level. The additional effect of adnexal findings was analysed. Sonographic identification of an ectopic pregnancy was very specific (0.99) but had low sensitivity (0.56) because many ectopics were not detected. The additional effect of HCG values on these results was minor. The low HCG cut-off levels advocated in recent studies are questioned by the results of our analysis: whereas the combined use of sonography and HCG measurements is shown to be of great benefit, the limitations are also documented, underlining the need for re-evaluation at intervals of patients with low HCG values. The question of which cut-off level should be used in practice, however, hinges on a difficult choice between a certain specificity and clinical utility.     

The Dall-Miles cable and plate system for periprosthetic femoral fractures

BACKGROUND: Spontaneous bilateral ectopic pregnancy is a rare event and difficult to diagnose preoperatively. CASE: A unique case occurred of bilateral ectopic pregnancy involving the left fallopian tube and right cornu, or interstitial segment. CONCLUSION: This case demonstrates the difficulty in diagnosing heterotopic pregnancies and in particular those pregnancies with an interstitial component and also demonstrates the limits of ultrasound and laparoscopy in making such a diagnosis.     

The spiritual and psychological explanations for loss experience

OBJECTIVE: To review the literature regarding the role of laparoscopy during pregnancy, particularly adnexal mass and non-obstetric surgery, incorporating the results of a series of 9 cases of laparoscopy during pregnancy at our centers. MATERIALS AND METHODS: A Medline search was performed to review the literature, and the reference lists provided by those articles were further explored for citations regarding laparoscopic adnexal surgery, appendectomy, and cholecystectomy. Our series of 9 patients consisted of pregnant patients with adnexal mass or acute abdomen who would otherwise have undergone exploratory laparotomy. Follow-up data for these 9 cases were collected by office visits, inquiry to the primary referring physicians, and telephone calls to the patient. RESULTS: The literature search yielded 42 additional cases of operative pelvic laparoscopy and 51 cases of abdominal operative laparoscopy (cholecystectomy and appendectomy). The publications, particularly regarding cholecystectomy, were supportive of the laparoscopic approach during pregnancy. All of the patients in our series had favorable outcomes. CONCLUSIONS: Advanced operative laparoscopy has been successfully performed for certain indications during pregnancy.     

Corpus luteum function and pregnancy rates with clomiphene citrate therapy: comparison of human chorionic gonadotrophin-induced versus spontaneous ovulation

A total of 508 clomiphene citrate cycles with intra-uterine insemination (IUI) performed in 233 consecutive patients were studied. In 247 cycles insemination was performed 36-38 h after human chorionic gonadotrophin (HCG)-triggered ovulation; in the remaining 261 cycles IUI was performed 18-20 h after urinary luteinizing hormone (LH) kit detection of a spontaneous LH surge. Corpus luteum function, as determined by luteal phase length and mid-luteal progesterone concentrations, together with pregnancy rates were analysed. There was no difference in luteal phase parameters between spontaneous and HCG-triggered cycles when adjusting for patient age. Furthermore, the pregnancy rates did not differ between the HCG and LH kit groups, even after adjusting for patient age and number of motile spermatozoa inseminated. Additionally, the large numbers of cycles analysed provided sufficient power to detect increases in clinical pregnancy rates in spontaneous ovulatory cycles and HCG-induced ovulation of 10.1 and 2.4% respectively, using the customary significance level (alpha-type error) of 0.05. These findings indicate that pregnancy rates and corpus luteum function in carefully monitored clomiphene citrate/IUI cycles do not differ between HCG-triggered and spontaneous ovulatory cycles.