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.     

Placental protein 14 in human in-vitro fertilization early pregnancies.

Placental protein 14 (PP14) and human chorionic gonadotrophin (HCG) were analysed in patients participating in an in-vitro fertilization-embryo transfer programme which did not include any kind of luteal support. Women with normal pregnancies, spontaneous abortions, ectopic pregnancies, biochemical pregnancies and non-pregnant women were compared. A combination of HCG and PP14 analyses distinguished between normal and abnormal implantation as early as 15 days after oocyte retrieval. The product of HCG (IU/l) and PP14 (micrograms/l) concentrations differed significantly between normal pregnancy, spontaneous abortion and ectopic pregnancy (P = 0.0248). It is concluded that both endometrial (PP14) and trophoblastic (HCG) markers, when used in combination, exhibit changes in abnormal implantation which may be clinically useful.     

Salpingectomy - the laparoscopic surgical choice for ectopic pregnancy

The aim of this study was to assess the fertility outcome afterectopic pregnancy (EP) treated by laparoscopic salpingectomy.Among the 375 patients who underwent this operation betweenJanuary 1983 and December 1993, there were 145 patients whodesired pregnancy and whose contralateral tube was not obstructed.The overall rate of intrauterine pregnancy (IUP) was 50.3%,with an EP rate of 15.2%, These results were analysed accordingto the patients‘ past history together with the conditionof the contralateral tube at the time of the laparoscopy. Wedefined two groups. Group 1 included patients who had no previoushistory of tubal surgery and whose contralateral tube was normal.Group 2 comprised those patients who had a previous historyof tubal surgery and/or those whose tube was pathological, butnot obstructed. Postoperative fertility of the patients in group1 was significantly higher than that of the patients in group2, with IUP rates of 75 and 36.6% respectively (P < 0.001),and a risk of EP recurrence of 9.6 and 183% respectively. Ingroup 1, the actuarial IUP rate at 24 months was significantlyhigher than that for the patients in group 2 (66.7 versus 36.9%;P < 0.001). The patient’s past history and the conditionof the contralateral tube were the two major factors relatedto fertility outcome after laparoscopic salpingectomy for EP.In patients with no past history of tubal surgery or infertilityand whose contralateral tube was normal, the fertility resultsafter laparoscopic salpingectomy appeared comparable to thoseobserved after conservative laparoscopic treatment     

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.     

The role of early post-implantation beta-HCG levels in the outcome of pregnancies following in-vitro fertilization

Daily plasma beta-HCG levels from days 11 to 18 after ovum retrieval(OR) were evaluated in a group of 73 women who became pregnantfollowing in-vitro fertilization and embryo replacement (IVF-ER).The 47 patients who had a normal ongoing pregnancy could bedistinguished from the 26 patients with a pathological pregnancy(pre-clinical abortion, clinical abortion and tubal pregnancy)by the mean daily beta-HCG levels, their mean daily increaseand the intercept and slope of the beta-HCG regression analysis.The mean daily beta-HCG levels of the normal pregnancies weresignificantly higher than: (i) pre-clinical abortions on days12–18 after OR; (ii) clinical abortions on days 12–16;and (iii) tubal pregnancies on days 12–17. Using quadraticdiscriminant analysis, normal and pathological pregnancies couldalso be distinguished by their absolute beta-HCG levels on day13 after OR with 27.6 mIU/ml being the cut-off point. Our resultsindicate that the outcome of pregnancy following IVF-ER couldbe predicted with a high degree of probability by monitoringdaily beta-HCG levels within the first 2 weeks following OR.     

Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx

The objective of this study was to assess the impact on pregnancyoutcome of excising hydrosalpinx(ges) in patients with repeatedin-vitro fertilization (IVF) failures. A group of 15 patientswho had previously undergone failed IVF attempts and had unilateralor bilateral hydrosalpinx was subjected to an operative laparoscopywith excision of the affected tube(s). Of these, 10 patientsunderwent a unilateral salpingectomy and five had a bilateralsalpingectomy. Stimulated cycles of IVF and/or cryo-thaw cycleswere then carried out post-salpingectomy and the results werecompared to those of pre-salpingec-tomy cycles. There was nostatistically significant difference between the number of matureeggs retrieved, peak oestra-diol concentrations, number of daysto human chorionic gonadotrophin administration, or number ofpre-zygotes frozen in the stimulated cycles pre- versus post-salpingectomy.Pre-salpingectomy, 15 patients underwent 38 stimulated cyclesand eight patients underwent 14 cycles with cryopreserved-thawedembryos, achieving one pregnancy from a fresh transfer thatresulted in a miscarriage. Post-salpingectomy, eight patientsunderwent 12 stimulated cycles, achieving five clinical pregnancies(two miscarriages and three ongoing pregnancies, i.e. eitherdelivered or a pregnancy >20 weeks), and nine patients underwent10 cycles with cryopreserved-thawed embryos, achieving fourclinical pregnancies (one miscarriage and three ongoing). Weconclude that excision of hydrosalpinx(ges) improves the pregnancypotential after IVF, and that new and repeat IVF patients shouldbe counselled accordingly.     

Pregnancy: Heterotopic pregnancies after in-vitro fertilization and embryo transfer

A total of 20 cases of heterotopic pregnancy were encounteredamong 2650 clinical pregnancies (0.75%) resulting from in-vitrofertilization/embryo transfer at Bourn Hall Clinic (Cambridge,UK) during the period July 1984-July 1993. The aetiology ofheterotopic pregnancy in the series is multifactorial, withtubal damage as the main factor. Transvaginal ultrasonographyshowed a high sensitivity for making correct diagnoses of heterotopicpregnancies compared with transabdominal ultrasonography (93.3versus 50.0%). The mean plasma human chorionic gonadotrophin(HCG) concentration on day 13 after embryo transfer was similarto those of uncomplicated intrauterine pregnancies and hencewas of no diagnostic value. The serial plasma HCG concentrationsof patients who delivered were significantly higher than forthose who aborted their intrauterine pregnancies (P < 0.01),although the sample of data available was too small to makefirm inferences. It does appear that serial HCG concentrationsmay have a predictive value of fair accuracy regarding the outcomeof the intrauterine pregnancy in heterotopic pregnancies. Theclinical presentations of the 20 cases at first examinationwere quite variable, with 45% (9/20) of patients asymptomatic.Tubal pregnancy in one patient resolved spontaneously, two caseswere treated by an injection of potassium chloride into thegestational sac and the remaining 17 cases were treated by salpingectomy.In 10 patients the intrauterine pregnancy resulted in live birthand the remaining 10 patients aborted spontaneously.     

Analysis of the incidence and risk factors associated with ectopic pregnancy following in-vitro fertilization and embryo transfer

Ectopic pregnancy is a well known complication of in-vitro fertilization(IVF) and embryo transfer. From March 1983 to December 1993,3000 clinical pregnancies were achieved at Bourn Hall Clinic,including 135 ectopic pregnancies (4.5%). Of these ectopics20 were heterotopic, eight ovarian, six bilateral tubal andthe remainder were singleton tubal pregnancies. The main riskfactor identified in the series was a history of pelvic inflammatorydisease (P < 0.001). The data also showed that ectopic pregnancyis at present more prevalent among patients in whom tubal damageis the reason for treatment. There was slight statistical evidence(P = 0.05) that patients having ectopic pregnancies receiveda higher volume of culture medium than those having normal deliveries.There was also an apparent trend (P = 0.07, not significant)that high progesterone/oestradiol ratio on the day of embryotransfer was associated with ectopic pregnancy. There was nostatistical evidence of association between ectopic pregnancyand a history of ectopic pregnancy, abortion, still birth, terminationof pregnancy, neonatal death, tubal surgery, ovarian stimulationprotocol, plasma concentration of oestradiol, luteinizing hormoneand progesterone, number of oocytes retrieved, number or qualityof embryos transferred, administration of general anaesthesiafor embryo transfer, and the number of patent Fallopian tubes.Awareness of the risk factors associated with ectopic pregnancyplays an important part in the early diagnosis of this potentiallyfatal condition.     

Pregnancy: Heterotopic pregnancy obtained after in-vitro fertilization and embryo transfer following bilateral total salpingectomy: case report

Heterotopic (coexistent ectopic and intra-uterine) pregnancyis common following in-vitro fertilization and multiple embryotransfer. Total bilateral salpingectomy is generally consideredto eliminate the risk of ectopic, and hence heterotopic pregnancy.This is, however, not strictly correct as it does not eliminatethe risk of interstitial tubal pregnancy. This is the firstreported case of a heterotopic pregnancy following total bilateralsalpingectomy. The diagnostic pitfalls and a suggested methodof avoiding them are discussed.     

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.     

Rare ectopic pregnancies after in-vitro fertilization: one unilateral twin and four bilateral tubal pregnancies

Between 1985 and 1989, one unilateral twin and four bilateral tubal pregnancies were encountered among 124 extrauterine pregnancies and 1648 intrauterine pregnancies following in-vitro fertilization and embryo transfer. The two factors associated with this high incidence of single and multiple extrauterine pregnancies were tubal damage and multiple embryo transfer. Embryos at different stages of development appear to have the capacity to implant ectopically. Despite advances in diagnostic capabilities, ectopic pregnancy remains a major cause of maternal mortality. Early diagnosis prior to rupture must be made if mortality and morbidity are to be abolished. The use of transvaginal sonography has improved the diagnosis of ectopic pregnancy and should be routinely used in all pregnancies following assisted conception. The identification of an intrauterine pregnancy should not be sufficient to rule out the possibility of an extrauterine pregnancy or even bilateral tubal pregnancies.     

Pregnancy: Determinants of reproductive prognosis after ectopic pregnancy

The reproductive prognosis of 115 women desiring pregnancy whounderwent surgery for ectopic pregnancy between 1985 and 1990at the Clinica Luigi Mangiagalli, was analysed after a medianfollow-up period of 26 months (range 2–83). Probabilityof reproductive events was assessed by a product-limit model.Women who underwent surgery for ectopic pregnancy had a 54%probability of becoming pregnant (cumulative pregnancy rate,CPR) and a 36% probability of giving birth to a child (cumulativelivebirth rate, CLB) during the 3 years after surgery. Thesepercentages dropped with history of previous ectopic pregnancy(respectively 33%, P = 0.07, and 7%, P < 0.05). Increasingage at surgery and presence of adhesions in the contra-lateraltube seemed to be associated with poor reproductive prognosis(CPR = 40% and CLB = 12% for women aged 35 years and CPR = 37%and CLB = 20% in women with adhesions in the contra-lateraltube), but these findings were not statistically significant.No association emerged between fertility and parity or typeof surgery. The recurrence rate of ectopic pregnancy was 20%.No significant association emerged between recurrence of ectopicpregnancy and age, history of previous pregnancy, history ofprevious ectopic pregnancy, non-intact contra-lateral tube andsalpingotomy.     

Pregnancy: Operative laparoscopy for ectopic pregnancy: how experienced should the surgeon be?

The purpose of this study was to assess the efficacy of laparoscopicsurgery for ectopic pregnancy in a general hospital in Paris,where most of the surgeons are still in training. During a periodof 20 months, 100 cases of ectopic pregnancy were diagnosedand treated by the attending residents. Nine cases requireda laparotomy due to heavy bleeding or interstitial ectopic pregnancy.Most of the other cases were treated laparoscopically, witheither salpingectomy (70 cases) or linear salpingostomy (19cases). Complications of the laparoscopic surgical procedureswere rare. There was one failure of linear salpingostomy thatrequired a second intervention (5.3% failure rate); there wasone case of urinary retention that resolved after 48 h; andone case of fever above 38°C that responded well to antimicrobialtherapy. In conclusion, we have shown that the current notionthat laparoscopic surgery is preferred to conventional abdominalsurgery for the treatment of ectopic pregnancy, can be appliedto a public gynaecological centre with young inexperienced residents,supervised by experienced gynaecologists.     

Case Report: Perforated appendicitis and ectopic pregnancy following in-vitro fertilization

This report describes a case of perforated appendicitis andectopic pregnancy following in-vitro fertilization (IVF) andembryo transfer. Perforated appendicitis was a coincidentalevent following IVF and embryo transfer. Immediate diagnosisand treatment of the perforated appendicitis saved the lifeof the patient. The ectopic pregnancy was completely resolvedwith two doses of methotrexate administration.     

Endovaginal sonography for the early diagnosis of intrauterine and ectopic pregnancies.

Endovaginal sonography, together with beta-HCG titre, was used to diagnose ectopic pregnancy in 58 patients. Transabdominal ultrasound failed to conclude this diagnosis. The data from endovaginal sonography revealed the presence of a gestational sac in all 15 patients with normal pregnancies at a beta-HCG level of 1042 mIU/ml. Of the 23 patients with pathological pregnancies only 61% had an intrauterine gestational sac. Only 15% of the 20 patients with ectopic pregnancies showed an increase in beta-HCG greater than 66% in 48 h, while in normal pregnancy, this increase was found in 71% of the patients. The endovaginal findings of the ectopic gestation revealed a complex adnexal mass in 55%, a cystic mass in 30% and fluid in the cul-de-sac in 20%. The diagnostic indices of adnexal and cul-de-sac sonographic findings in the ectopic group further improved specificity and positive predictive accuracy. The detection of ectopic versus intrauterine gestation showed a high sensitivity of 95%, a specificity of 100%, a positive predictability of 100% and a negative predictability of 97%. The data confirm the value and reliability of endovaginal and cul-de-sac sonography, combined with measurement of the beta-HCG level in the early diagnosis of ectopic pregnancy. This combined approach not only makes the differentiation between normal and extrauterine gestation more accurate but also helps to avoid unnecessary diagnostic laparoscopy and hospitalization.     

Luteal function associated with single, multiple and ectopic embryo implantation in natural cycles or after ovarian hyperstimulation for in-vitro fertilization/gamete intra-fallopian transfer

Levels of reproductive steroids and gonadotrophins were analysed retrospectively during the peri-implantation period following non-conceptional and conceptional natural cycles and in cycles associated with ovarian hyperstimulation for in-vitro fertilization or gamete intra-Fallopian transfer. In cycles not associated with conception, the luteal phase of hyperstimulated cycles (n = 100) was characterized by higher serum progesterone and oestradiol levels (P less than 0.01) and with an earlier decline in steroids than in natural cycles (n = 21). On day 11 (day of oocyte recovery = day 0), the level of progesterone in twin (n = 59) and triplet (n = 13) pregnancies was higher than singleton pregnancies (n = 176) (P less than 0.006, P less than 0.006 respectively) while those destined to abort (n = 66) had lower progesterone levels (P less than 0.01). Ectopic implantation (n = 11) had the lowest progesterone concentrations on day 11 (P less than 0.01) and this may imply a delay in corpus luteum rescue or a later implantation time than intrauterine conception.     

Selective drop-out in successive in-vitro fertilization attempts: the pendulum danger.

Success rates from in-vitro fertilization (IVF) in the long term are dependent on selection procedures with regard to continuation into further IVF episodes. Publications on success rates in successive episodes will give incentives to adapt selection criteria, but if these publications do not deal explicitly with patient selection, the adaptations might change their direction every time: the pendulum danger.     

Evaluation of the sites of ectopic pregnancies subsequent to reconstructive tubal surgery

The sites of ectopic pregnancies in women who underwent varioustypes of reconstructive tubal surgery were analysed and comparedto the controls. Overall, ectopic pregnancies subsequent toall types of tubal surgeries were more often implanted proximallycompared to the control population.     

Bilateral salpingectomy does not compromise ovarian stimulation in an in-vitro fertilization/embryo transfer programme

The question whether salpingectomy has a negative influenceon ovarian function and the outcome of pregnancy in an in-vitrofertilization (IVF) and embryo transfer treatment programmeis not yet answered. We performed a retrospective case-controlstudy to investigate the possible negative effect of salpingectomyon ovarian response to human menopausal gonadotrophins (HMG)during IVF and embryo transfer. The study group was composedof 26 patients with bilateral salpingectomy. In 67 cycles weanalysed different parameters of ovulation such as the numberof days of ovarian stimulation, numbers of ampoules of HMG,pre-ovulatory oestradiol concentrations and the numbers of oocytesretrieved. These parameters were compared to a control groupof 134 cycles in 134 women with healthy Fallopian tubes. Nodifferences were found. Implantation ratio, pregnancy rate andoutcome were the same in both groups. We conclude that bilateralsalpingectomy had no detrimental effect on ovarian performanceduring IVF and embryo transfer treatment nor on the outcome.     

Analysis of the fourth to eighth in-vitro fertilization treatments after three previously failed attempts

The fourth to eighth in-vitro fertilization cycles of patientswho had previously reached the stage of embryo transfer withoutconceiving were evaluated. A total of 426 cycles were reviewedin women ranging in age from 25 to 46 years. The patients underwentfrom four (169 women) to eight (27 women) treatment cycles,using four established protocols for induction of ovulation.There was no statistical difference in the age, aetiology, durationof infertility and distribution of the various protocols amongthe analysed groups. The pregnancy rates in cycles 4–8were 19.5, 15.4, 10.8, 16.7 and 11.8% respectively (mean 16.2%per cycle) and were not statistically different. There was notrend of reduced success when the number of attempts increased.The overall live birth rate was 12.4%. The pregnancy rate wascomparable between age groups. No protocol proved to be significantlysuperior to others when pregnancy rate per embryo transfer wasassessed. We concluded that the pregnancy rate in cycles 4–8was stable, including those of patients up to 42 years of age.Continuous efforts are therefore advised for at least up tothis age and number of attempts. A change of an induction protocolin subsequent cycles, after repeated failure, is not statisticallyjustified