Analysis of ectopic pregnancies resulting from in-vitro fertilization and embryo transfer

The purpose of this study was to analyse the risk factors, stimulation characteristics, site and outcome of pregnancy and future fecundity of patients who develop ectopic pregnancies after in-vitro fertilization (IVF). Of 3145 transfer cycles between January 1981 and July 1989, 27 (3.3%) of the resulting 825 pregnancies were ectopic. There was a significantly greater incidence of a prior ectopic pregnancy in the study group compared to the controls. Compared to matched controls with intrauterine pregnancies, the study group had significantly higher peak oestradiol levels. Twenty-one ectopic pregnancies were ampullary, two were interstitial, one was abdominal, one was cervical and two were heterotopic. Sixteen of the patients subsequently underwent 40 IVF attempts with a pregnancy rate of 28% per transfer. We conclude that patients with a prior ectopic pregnancy are at risk for an IVF ectopic pregnancy. The subsequent IVF outcome of those who develop ectopic pregnancies after IVF is encouraging.     

Reproductive outcomes of women with a previous history of Caesarean scar ectopic pregnancies

BACKGROUND: Caesarean scar ectopic pregnancy is associated with a number of significant complications. In this study, we report on subsequent reproductive outcomes in a group of women following successful treatment of their scar pregnancies. METHODS: The study included those women who received treatment for their Caesarean scar pregnancies between April 1999 and October 2005. Their ability to conceive, the time it took to become pregnant and outcomes of subsequent pregnancies were all recorded. RESULTS: 40 women with Caesarean scar pregnancies were managed in our unit. The uterus was conserved in 38/40 cases. Follow-up data were available in 29/38 (76%) of women. Twenty-four out of 29 (83%) attempted to become pregnant. Twenty-one out of 24 [88%, 95% confidence interval (CI): 75-100] women conceived spontaneously. Twenty out of 21 (95%, 95% CI: 86-100) pregnancies were intrauterine and one woman (5%, 95% CI: 0-14) had a recurrent scar ectopic. Thirteen out of 20 (65%, 95% CI: 44-86) intrauterine pregnancies appeared normal. Nine out of 13 (69%) were delivered by Caesarean section. Seven out of 20 (35%, 95% CI: 14-56) intrauterine pregnancies ended in spontaneous abortions. CONCLUSIONS: Our study shows that reproductive outcomes following treatment of caesarean scar ectopic pregnancies are favourable. The risk of complications including recurrent scar implantation appears to be low.     

Fertility outcome after ectopic pregnancy and use of an intrauterine device at the time of the index ectopic pregnancy

Fertility after ectopic pregnancy (EP) was investigated in a non-selected population taking into account intrauterine device (IUD) use at the time of the EP. Between January 1992 and June 1996, 647 women listed in the EP register of Auvergne (France) were followed up. The analysis included only the 328 women who were seeking to become pregnant: 23 women using IUD at the time of the index EP (IUD users) and 305 IUD non-users. Among IUD users, there was no recurrence of EP, and the 1 year cumulative rate was 87% [95% confidence interval (CI): 73-100%] for intrauterine pregnancies and 86% (95% CI: 72-100%) for deliveries. Among IUD non-users, the 2 year cumulative rate for recurrence of EP was 28% (95% CI: 17-39%), and the 1 year cumulative rates were 60% (95% CI: 53-66%) for intrauterine pregnancies and 44% (95% CI: 38-56%) for deliveries. The adjusted intrauterine pregnancy rate of IUD users was not significantly different from that of IUD non-users. However, IUD non-users had more miscarriages, so their delivery rate was lower.     

Pregnancy-associated plasma protein A in pregnancy-related gynaecologic emergency

Serum concentrations of pregnancy-associated plasma protein A (PAPP-A) were measured in patients with pregnancy-related gynaecologic emergencies including ectopic pregnancy (n = 124) and intrauterine abortion (n = 40). The results were compared with those in normal pregnancy (n = 136) and non-pregnant women (n = 460). In ectopic pregnancy and intrauterine abortion, the PAPP-A levels were lower than in normal pregnancy. In patients with a pregnancy-related gynaecologic emergency PAPP-A was undetectable in 82% of the ectopic pregnancies and in 55% of the intrauterine abortions. Considering the frequency of ectopic pregnancy (35.8%) and intrauterine abortion (52.3%) among all patients with pregnancy-related disorders, the likelihood that a pregnant patient with undectable PAPP-A has an ectopic pregnancy is 30%, and intrauterine abortion is 29%. These results indicate that although PAPP-A levels in ectopic pregnancy and intrauterine abortion are lower than in normal pregnancy, PAPP-A measurement cannot be used to distinguish between ectopic pregnancy and intrauterine abortion.     

Rare association of ovarian implantation site for patients with heterotopic and with primary ectopic pregnancies after ICSI and blastocyst transfer

Two cases of patients with ruptured ovarian pregnancies (P1 = ovarian heterotopic and P2 = primary ovarian ectopic) after intracytoplasmic sperm injection and blastocyst transfer are presented. Laparoscopy was performed on day 40 and day 27 after transfer in cases P1 and P2 respectively. In both cases the ectopic pregnancies were located on the left ovary and were successfully removed by laparoscopy preserving the ovaries. In case P1 the intrauterine pregnancy was not affected. A healthy boy was born after 37 weeks of pregnancy. In this way, potential fertility of the patients and the intrauterine pregnancy were maintained. These cases occurred during a series of blastocyst transfers in which 129 pregnancies were obtained. There were no cases of ovarian ectopic/heterotopic pregnancies from January 1996 to September 1999 in 814 pregnancies obtained from day 2 or day 3 embryo transfers. Because the ovarian ectopic pregnancies occurred in patients with day 5 embryo transfer who otherwise did not have any predisposing factors for ectopic pregnancy, it is advisable to conduct a large scale analysis of future data about the possible association between blastocyst-stage embryo transfer and the somewhat higher risk of unexpected complications of clinical outcome.     

Simultaneous intrauterine and ectopic pregnancies following in-vitro fertilization and gamete intra-fallopian transfer. A review of nine cases

This paper reports nine cases of simultaneous intrauterine and ectopic pregnancies which followed in-vitro fertilization (three cases) and gamete intra-Fallopian transfer (six cases). The ectopic pregnancies were treated by aspiration and injection of potassium chloride and methotrexate (five cases), salpingectomy (three cases) or laparoscopic evacuation (one case). In five of the nine patients the intrauterine pregnancies continued until after the 35th week and the patients delivered live infants. The role of vaginal ultrasound scanning in making the diagnosis was emphasized. The literature on heterotropic pregnancy is reviewed.     

Vascular endothelial growth factor (VEGF) and discrimination between abnormal intrauterine and ectopic pregnancy

BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) levels in women with abnormal intrauterine and ectopic pregnancies (EP) at 6 weeks gestation. METHODS: We conducted a prospective case-control study comparing serum VEGF concentrations among 84 women with abnormal intrauterine and EP matched for gestational age (42 women in each group). We analysed whether serum VEGF levels >200 pg/ml would discriminate between abnormal intrauterine pregnancies and EP at 6 weeks gestation, and we calculated sensitivity, specificity and positive predictive values. RESULTS: Serum VEGF concentrations did not show statistically significant differences between women with abnormal intrauterine pregnancies (median, 198.5 pg/ml; range, 0-701.6) and EP (median, 211.2 pg/ml; range 0-628.8). When threshold concentrations of a serum VEGF level >200 pg/ml were used, abnormal intrauterine pregnancy could be distinguished from EP with a sensitivity of 56%, a specificity of 51%, and a positive predictive value of 53%. CONCLUSIONS: VEGF does not discriminate ectopic from abnormal intrauterine pregnancies at 6 weeks gestation, and thus should not be used in clinical management.     

Are pregnancy-associated plasma protein-A (PAPP-A) and CA 125 measurements after IVF-ET possible predictors of early pregnancy wastage?

Pregnancy-associated plasma protein-A (PAPP-A), a macromolecular glycoprotein of placental origin, was reported to be depressed in established ectopic pregnancies. CA 125 is a known marker for ovarian cancer found to be elevated during the first trimester of pregnancy and in women with pelvic inflammatory disease. The present study investigated the usefulness of these parameters to predict the outcome of pregnancy in asymptomatic patients with a positive pregnancy test after in-vitro fertilization and embryo transfer (IVF-ET). Blood samples (n = 159) were obtained at different periods of time post-ET from 39 women, 21 of whom experienced a normal pregnancy, 12 had an intrauterine abortion and six had an ectopic pregnancy. PAPP-A and CA 125 were measured by radioimmunoassays. From day 30 onwards in normal pregnancies, PAPP-A was significantly increased over non-pregnant controls. In the spontaneous abortion group, the levels of PAPP-A were significantly lower than in normal pregnancy but higher than in non-pregnant controls. In ectopic pregnancy, PAPP-A remained at the level of non-pregnant controls throughout the entire observation period. CA 125 was significantly increased in all types of pregnancy. However, in two cases of hyperstimulation followed by a normal pregnancy and in four cases of ectopic pregnancy with signs of peritoneal irritation (hydrosalpinx, ruptured ectopic or salpingitis) the levels of CA 125 were 15-50 times higher than in normal pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)     

体外受精-胚胎移植后异位妊娠11例临床分析

目的　探讨体外受精 -胚胎移植后异位妊娠的发生原因、诊断及治疗方法。方法　对体外受精 -胚胎移植后妊娠 10 4例临床资料进行回顾性分析。结果　 10 4例中宫内妊娠 93例 ,异位妊娠 11例 ,异位妊娠率为 10 6 %(11/10 4 )。因输卵管性不孕行IVF的异位妊娠发生率为 13 9%(10 /72 ) ,远远高于因其它原因不孕致异位妊娠发生率的 3 1%(1/32 ) (P<0 .0 5 )。宫外孕组ET时插管困难者发生率为 36 4 %(4 /11) ,而宫腔内妊娠ET时插管困难发生率为 16 1%(15 /93) ,两者之间无显著性差异 (P >0 .0 5 )。结论　 1 异位妊娠的发生与输卵管病变有关 ;2 孕早期血hCG及阴道超声检查有助于异位妊娠诊断及治疗     

Distinction between early normal intrauterine pregnancies and pathological pregnancies by means of a logistic model.

The probability of an unclear very early pregnancy being a normal intrauterine pregnancy was estimated using a logistic model. Five diagnostic measures of prognostic value were identified in the model: (i) daily change in human chorionic gonadotrophin (HCG), (ii) results of transvaginal ultrasound, (iii) vaginal bleeding, (iv) serum progesterone level and (v) risk score for ectopic pregnancy. With the use of this model, the probability of a normal intrauterine pregnancy has been estimated as 96.7%.     

Ultrasound-guided hydrosalpinx aspiration during oocyte collection improves pregnancy outcome in IVF: a randomized controlled trial

BACKGROUND: Hydrosalpinges have adverse effects on IVF outcomes. Salpingectomy is effective in improving outcomes, but it is not always practical or safe. Ultrasound-guided aspiration of hydrosalpinges at oocyte collection is an option for those who develop hydrosalpinges during controlled ovarian stimulation; however, there is no randomized evidence to show whether this practice is effective. METHODS: Between October 1999 and June 2003, consenting women of age 相似文献   

Day 14 maternal serum progesterone levels predict pregnancy outcome in IVF/ICSI treatment cycles: a prospective study

BACKGROUND: Serum progesterone has been advocated as a tool in the diagnosis of early pregnancy failure. We conducted this prospective study in order to investigate the potential value of early (14 days after oocyte recovery) serum progesterone measurement, in women undergoing IVF/ICSI and receiving rectal progesterone supplements, in relation to pregnancy outcome. METHODS: 442 women consecutively treated by IVF or ICSI had serum progesterone and bhCG levels prospectively measured 14 days after oocyte retrieval (day 0). All women received natural progesterone 400 mg rectally until the pregnancy test on day 14. Pregnant women were followed up by serial transvaginal ultrasound scans to 8 weeks gestation. RESULTS: 115 women (26%) had a viable intra-uterine pregnancy at 8 weeks gestation, 80 (18.1%) had an abnormal pregnancy (biochemical, ectopic, miscarriage) and 247 (55.9%) failed to conceive. Women with on-going pregnancies had significantly higher serum progesterone levels (median: 430, 95%CI: 390-500 nmol/l) compared to those who had either an abnormal pregnancy (72, 48-96 nmol/l; P < 0.001) or failed to conceive (33, 28-37 nmol/l; P < 0.001). Receiver-operator curve analysis demonstrated that a single serum progesterone on day 14 post-oocyte retrieval, could highly differentiate between normal and abnormal pregnancies (area under the curve = 0.927, 95%CI = 0.89-0.96; P < 0.0001). CONCLUSIONS: In spite of exogenous progesterone supplementation, serum progesterone levels, from as early as 4 weeks gestation (day 14 post-oocyte retrieval) were significantly elevated and predicted women destined to have viable intra-uterine pregnancies. These high levels are suggestive that endogenous progesterone is already sufficient in viable pregnancies and that exogenous progesterone administration will not rescue a pregnancy destined to result in a miscarriage. Single serum progesterone measurement could be a useful indicator of pregnancy outcome in women undergoing IVF or ICSI treatment.     

Fertility after ectopic pregnancy: first results of a population-based cohort study in France

The purpose of this paper was to evaluate the reproductive outcomeafter ectopic pregnancy (EP) from a population-based registerin the centre of France. Since 1992, all the women aged 15–44years, who permanently reside in the target area and who weretreated either by surgical or medical procedures for an ectopicpregnancy in one of the area centres, have been registered andprospectively followed until 45 years of age. The analysis presentedwas based on the 155 women registered between January 1992 andMarch 1994 who were followed up for at least 6 months, and whowere seeking a new pregnancy. The mean follow-up period was16 months. A total of 102 women (66%) obtained a pregnancy.The first conception was intrauterine for 92 women, and 10 hada recurrence of ectopic pregnancy. Risk factors of recurrencewere prior spontaneous abortion and prior tubal damage. Forthose women who conceived, the mean time to obtain pregnancy(’time to pregnancy‘) was 4.8 months. The 1 yearcumulative intrauterine pregnancy rate (i.e. the probabilityof obtaining an intrauterine pregnancy within 1 year of seekingpregnancy) was 70%. After multivariate analysis by a Cox regression,the factors associated with higher fertility were age < 30years, high educational level and no prior tubal damage.     

Heterotopic pregnancy associated with gamete intra-fallopian transfer.

Recent reports in the literature have focused on the increased risk of heterotopic pregnancy after the transfer of multiple concepti or oocytes. In an international collaborative patient registry between 1985 and 1989, 601 clinical pregnancies resulted from 2092 gamete intra-Fallopian transfer (GIFT) retrieval cycles. Five of the pregnancies were heterotopic (0.83%). After surgical intervention, all five cases of combined gestation resulted in live birth from intrauterine pregnancies. Routine vaginal ultrasonographic examination of the adnexa in patients who conceive after GIFT may help early diagnosis of heterotopic pregnancy. If the diagnosis is made early, conservative treatment may preserve the future fecundity of the patient and more intrauterine pregnancies may be salvaged.     

Heterotopic pregnancies after in-vitro fertilization and embryo transfer--a Danish survey

Thirteen cases of heterotopic pregnancy were diagnosed among1171 pregnancies established in Denmark after in-vitro fertilizationand embryo transfer (IVF-ET). Thus the frequency of heterotopicpregnancy was 13/1171 or 1.1%. In five cases the diagnosis ofheterotopic pregnancy was made by ultrasound at 6–9 weeksof gestation; three of these patients were asymptomatic, whiletwo patients presented with abdominal pain and vaginal bleeding.All these patients had an unruptured ectopic pregnancy. Eightcases were diagnosed at the time of surgery; all these patientspresented with abdominal pain. Only two of the 13 patients hadvaginal bleeding. In nine of the 13 cases the intra-uterinepregnancy resulted in term delivery, while one pregnancy isongoing. In pregnancies following IVF-ET, this diagnosis shouldparticularly be considered in cases with abdominal pain; vaginalbleeding may be absent. Ultrasound examination may lead to earlydiagnosis even in asymptomatic cases. In most cases, removalof the ectopic gestation will allow the intrauterine pregnancyto proceed to term.     

Transvaginal ultrasound-guided embryo transfer improves pregnancy and implantation rates after IVF.

BACKGROUND: Attempts are constantly being made to improve clinical pregnancy rates after IVF and embryo transfer. Since November 1998, we have gradually been adopting transvaginal ultrasound guidance during embryo transfer. We retrospectively examined the efficacy of this method on pregnancy and implantation rates. METHODS: The results of 846 cycles from our IVF-embryo transfer programme were analysed and comparisons were made between those carried out using ultrasound guidance and those by the clinical touch method. RESULTS: Higher pregnancy and implantation rates (28.9 and 15.2% respectively) were found in the group using the transvaginal ultrasound guidance during embryo transfer compared with those in the group using the clinical touch method (13.1 and 7.0% respectively). The differences were statistically significant (P < 0.01). There was no significant difference in ectopic pregnancy rates between the two groups. CONCLUSION: The use of transvaginal ultrasound-guided embryo transfer significantly improved both pregnancy and implantation rates. Although technically difficult, we suggest its use may maximize the chances of achieving a successful pregnancy outcome.     

Ultrasound-guided embryo transfer does not offer any benefit in clinical outcome: a randomized controlled trial

BACKGROUND: Ultrasound-guided embryo transfer (ET) is widely suggested as a standard clinical practice that improves overall embryo implantation and pregnancy rates. Various studies of this issue suffer from methodological pitfalls, so that a randomized controlled trial, which overcomes these problems, might be valuable. METHODS: Three hundred women aged <40, who underwent fresh ET, were included in this randomized, double-blind controlled trial. The K-J-SPPE echo tip soft catheter was used for the ultrasound-guided ET and the traditional K-Soft catheter for ETs not using ultrasound. One experienced operator performed all ETs. The primary study outcome was overall pregnancy rate (defined as the number of positive hCG results per transfer). RESULTS: No significant differences between groups were found regarding baseline patient and embryological characteristics, except for male factor and unexplained infertility (higher in the blind and ultrasound-guided ET group, respectively, P < 0.05). Overall pregnancy rates were 53.3 and 51.3% in the ultrasound-guided and blind ET group, respectively. Two ectopic pregnancies were reported in each group. Difficulty in cervical negotiation did not differ between the two groups. CONCLUSIONS: In patients undergoing ET by an experienced operator, ultrasound guidance did not provide any benefit in terms of overall clinical pregnancy and embryo implantation rates.     

The use of fibrin sealant for embryo transfer: development and clinical studies.

Many embryo transfers after in-vitro fertilization may fail because of expulsion of the embryos from the uterus. Approximately 5-8% of pregnancies resulting from embryo transfer are ectopic. The aim of our study was to find a technique to avoid ectopic pregnancies and to improve the pregnancy rate. We used a two-component fibrin sealant which also contains a fibrinolysis inhibitor (aprotinin) at various concentrations. After gaining experience with mouse embryos, the sealant was used in human embryo transfer with great success. The results of a pilot study encouraged us to perform a prospective randomized study on 546 patients (270 with fibrin sealant, 276 conventional embryo transfers). There were 47 (17.0%) orthotopic pregnancies and 6 (2.2%) ectopic pregnancies in the control group, whereas there were 51 (18.9%) intrauterine and no ectopic pregnancies in the treatment group. The difference in ectopic pregnancies was statistically significant (P less than 0.05). With regard to the aprotinin concentration, there was a trend towards better results with 100-150 kIU (28.5% clinical pregnancies) in comparison to 250-300 kIU (19.2%) or no aprotinin (20.4%) (not significant). Further improvements of the technique may raise the pregnancy rate when fibrin sealant is used. As shown in our prospective randomized study, ectopic pregnancies may be completely avoided.     

Pregnancy: The prediction of ectopic pregnancy after in-vitro fertilization and embryo transfer

Data from 135 patients who suffered ectopic pregnancies andfrom 135 patients who progressed to singleton deliveries afterin-vitro fertilization and embryo transfer have been analysedretrospectively. The ectopic pregnancies represent all suchcases observed at Bourn Hall Clinic between 1983 and 1993. Thedelivered group was randomly selected from the same time period.The ectopic pregnancies included 20 heterotopic, eight ovarianand six bilateral tubal pregnancies; the remainder were singletontubal pregnancies. The aim of this study was to identify thevariables which differed systematically for the two groups ofpatients and to explore whether such variables could be usedto predict ectopic pregnancy at an early stage. The mean plasmaconcentration of human chorionic gonadotrophin and progesteronefor the ectopic pregnancy group was significantly lower thanthat for the singleton delivery group (P < 0.001). However,there was such a degree of overlap that it was impossible todevise a cut-off concentration for either hormone which wouldoffer a clinically useful predictor of ectopic pregnancy. Nevertheless,using the discriminant function analysis of these data, togetherwith the history of pelvic inflammatory disease, we could predictup to 90% of cases of ectopic pregnancy by day 23 after embryotransfer, long before ultrasound imaging would be useful.