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.     

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.     

Comparison of in-vitro fertilization in male and tubal infertility: a 3 year survey.

The in-vitro fertilization and embryo transfer (IVF-ET) procedure was compared in 175 couples with male infertility and 480 couples with tubal infertility. In cases of male infertility, more oocytes were recovered but fewer oocytes were fertilized. Although the cleavage rate was decreased, no difference in embryo quality was found. In male infertility, fewer transfers were performed and the average number of embryos per transfer was lower. The total pregnancy rate was also lower per cycle (12.8 versus 22.9%), but not per transfer (25.4 versus 25.7%). The further obstetrical outcome was similar in both groups. We conclude that male infertility can be treated by IVF-ET but results are still disappointing when compared to a control group with normal spermatozoa.     

Falloposcopic comparison of unilateral and bilateral proximal tubal ocdusive disease

The purpose of this study was to compare the appearance of theentire length of the oviductal canal in women with unilateralversus bilateral proximal tubal occlusion. Eleven women hadapparent unilateral disease and 18 had apparent bilateral occlusion.Proximal occlusion was confirmed both by hysterosalpingographyand laparoscopy. Falloposcopic examination was performed byretrograde visualization using the linear eversion catheter,in office. Bilateral apparent proximal occlusion was found tohave a significantly higher incidence of actual proximal occlusionand distal intralumenal abnormalities. However, five proximalsegments and six distal segments were found to be abnormal wherethe pre-examina-tion diagnosis was unilateral occlusion. Furthermore,the contralateral oviductal canal was found to be abnormal infour women with apparent unilateral disease, indicating thatapparent unilateral proximal tubal occlusion is associated withactual pathology. These data demonstrate the value of intralumenalassessment of apparent proximal occlusion.     

Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals

In singleton pregnancies after in-vitro fertilization (IVF), increased rates of obstetric and perinatal complications have been reported. Studies that compared IVF twin pregnancies with spontaneously conceived twins have yielded conflicting results. We compared 96 IVF twin pregnancies to 96 controls after elaborate matching. The design of our study precluded matching by zygosity. The monozygosity rate was higher in the control group and this implies that beforehand the risk for a less favourable outcome in the control group was higher than in the IVF group. However, the average birthweight of the IVF children was less than that of children in the control group (P = 0.04). This was not due to more intrauterine growth retardation in the IVF group. The mean gestational age at birth was 5 days shorter in IVF than control pregnancies, and although this difference was not significant it might explain the lower birthweight in the IVF group. The discordance rate in the IVF group was significantly increased. We found no difference in perinatal mortality and morbidity. We conclude that this study provides further evidence for a different outcome of IVF twin pregnancies in comparison with spontaneously conceived twin pregnancies.     

Transfusion-dependent homozygous {beta}-thalassaemia major: successful twin pregnancy following in-vitro fertilization and tubal embryo transfer

Homozygous -thalassaemia (thalassaemia major) is a severe, transfusion-dependentanaemia that also causes infertility due to endocrine impairment.Very few pregnancies are reported among such patients and thereis only one report in the literature referring to a pregnancyachieved with ovulation induction and intra-uterine insemination.We report here the first successful twin pregnancy followingin-vitro fertilization and tubal embryo transfer in a transfusion-dependenthomozygous -thalassaemic woman with an oligoastheno-zoospermicpartner. Prior to ovarian stimulation, desferrioxamine was discontinueddue to potential fetotoxicity. Pre-gestational transfusionaland chelating therapies were resumed after delivery. In suchpatients, ovulation induction and assisted reproductive techniquesappear crucial in achieving pregnancy with concurrent haematologicalbalance without desferrioxamine administration.     

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.     

Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection

Since the advent of assisted reproductive technology, the concernabout ectopic implantation of embryos has increased dramatically.Simultaneous bilateral tubal pregnancy is the least common typeof ectopic implantation of two embryos. In this report we presentthe first case of simultaneous bilateral tubal pregnancy afterintracytoplasmic sperm injection (ICSI) and embryo transfertreatment. The present case had no risk factor for ectopic pregnancy.Therefore, for early diagnosis and management of such cases,close clinical follow-up and routine ultrasonography followingICSI are necessary.     

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.     

Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial.

A prospective randomized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) was carried out. First, top quality embryo characteristics were delineated by retrospectively analysing embryos resulting in ongoing twins after double embryo transfer. A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and <20% cellular fragments on day 2 and day 3 after fertilization. Using these criteria, a prospective study was conducted in women <34 years of age, who started their first IVF/ICSI cycle. Of 194 eligible patients, 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospectively randomized. In all, 26 single embryo transfers resulted in 17 conceptions, 14 clinical and 10 ongoing pregnancies [implantation rate (IR) = 42.3%; ongoing pregnancy rate (OPR) = 38.5%] with one monozygotic twin; 27 double embryo transfers resulted in 20 ongoing conceptions with six (30%) twins (IR = 48.1%; OPR = 74%). We conclude that by using single embryo transfer and strict embryo criteria, an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI, while limiting the dizygotic twin pregnancy rate to its natural incidence of <1% of all ongoing pregnancies.     

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.     

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 dilemma of the optimal surgical procedure in ectopic pregnancies occurring in in-vitro fertilization.

Ectopic pregnancy remains one of the undesired sequelae of in-vitro fertilization (IVF) treatment. It seems that mechanical infertility increases the risk of this complication in IVF. Thus, the surgeon treating such a case faces the dilemma of the optimal surgical procedure because of the increased risk for repeated ectopic pregnancy in subsequent IVF cycles. Two cases are presented with repeated ectopic pregnancy occurring in IVF. One case underwent salpingectomy on the first occasion and eventually developed a contralateral repeat ectopic gestation ending with salpingectomy. The second case underwent a conservative salpingotomy in the first event and developed a repeated ectopic gestation on the same side, undergoing bilateral salpingectomy. In order to prevent repeated ectopic pregnancies in an IVF programme, a definitive surgical procedure, such as bilateral salpingectomy, should be considered in the first episode in patients referred for IVF because of tubal pathology.     

Cervical ectopic twin pregnancy: diagnosis and conservative treatment: case report

A case of cervical ectopic twin pregnancy with cardiac activity in both embryos is presented. It was diagnosed in the eighth week of gestation by ultrasonography, and treated conservatively with intra-amniotic administration of methotrexate under ultrasonographic guidance followed by curettage. This procedure allows subsequent gestations.     

Heterotopic triplet pregnancy: report of a case with bilateral tubal pregnancy and an intrauterine pregnancy

The first report of an ectopic pregnancy following IVF was published in 1976, and since then heterotopic pregnancies (HPs) have been reported at an increasing rate. Although cases of the co-existence of a bilateral tubal and an intrauterine pregnancy following IVF-embryo transfer have been reported, a case of heterotopic triplet pregnancy caused by unilateral tubal embryo transfer has not yet been published in the literature. Here we report on a 38-year-old women (gravida 3, para 1) with a history of infertility who presented to our infertility clinic for evaluation. Hysterosalpingography revealed bilaterally patent Fallopian tubes and stricture of the cervical canal. She conceived after receiving HMG combined with pure FSH, followed by IVF-tubal embryo transfer. Four embryos were replaced into the right tube. Approximately 5 weeks after tubal embryo transfer, the patient presented with lower abdominal tenderness and shock due to internal bleeding. She underwent an emergency laparotomy under the impression of HP. Bilateral tubal pregnancy with right tubal rupture was noted during the operation. The post-operative course was uneventful. Early intervention and thorough inspection of the peritoneal cavity in patients with haemodynamic instability can prevent jeopardizing the life of the mother as well as the ongoing pregnancy.     

Successful in-vitro fertilization in a natural cycle after four previously failed attempts in stimulated cycles: case report.

A case is reported of successful in-vitro fertilization (IVF) and pregnancy in a natural cycle after four previously failed attempts with stimulated cycles. The patient began treatment at the age of 36 years and underwent four stimulated IVF cycles, each time with three embryos of good quality transferred. In one attempt, three cryopreserved embryos were transferred in a natural cycle. The patient failed to conceive. At the age of 38 years, the patient was entered into a natural cycle IVF programme. The patient conceived twice in each of her first two attempts but unfortunately aborted. In her third natural cycle of IVF, again with one oocyte obtained and one embryo transferred, the patient conceived and had a full term gestation. It is concluded that IVF in a natural cycle is a viable option for infertile women with blocked Fallopian tubes who have normal ovulatory menstrual cycles.     

Delivery rates after in-vitro fertilization following bilateral salpingectomy due to hydrosalpinges: a case control study.

This retrospective case-control study assessed the impact of bilateral salpingectomy due to uni- or bilateral hydrosalpinges on the outcome of in-vitro fertilization (IVF) in a large consecutive series of patients. The effect of bilateral salpingectomy due to hydrosalpinges on pregnancy outcome was compared in 139 patients (263 cycles) and 139 age-matched controls with tubal infertility without hydrosalpinges (296 cycles). The delivery rates per initiated cycle as well as the implantation rates were equal in the two groups (21.7 versus 21.6% and 19 versus 21%). The number of embryos, the cleavage stage, and the embryo morphology score were equal in the two groups. Among 92 patients treated with 182 IVF cycles who underwent salpingectomy between 1.5 and 5 years prior to their first IVF cycle, the delivery and the implantation rates were 22.5 and 20.5% respectively. Of the patients with salpingectomy after an average of 1.7 failed IVF cycles and who re-entered the IVF programme 3 and 6 months subsequent to surgery, 47 were treated with 83 IVF cycles. The live birth and the implantation rates after surgery in this group were 20.5 and 20% respectively. It is concluded that bilateral salpingectomy due to hydrosalpinges restores a normal delivery as well as implantation rate after IVF treatment compared to controls. A favourable outcome is also found in patients operated on after repeated IVF failures. Furthermore, a normal live birth rate as well as a high implantation rate is maintained for at least three IVF cycles subsequent to surgical treatment.     

Surgery: Microsurgery and in-vitro fertilization and embryo transfer for infertility resulting from pathological proximal tubal blockage

The aim of this study was to evaluate the prognosis for thepatients after the treatment of infertility resulting from proximaltubal blockage using microsurgical tubocornual anastomosis andin-vitro fertilization (IVF) and embryo transfer complementarity.A total of 59 microsurgical operations (1986–1992) forinfertility resulting from pathological proximal tubal lesionswere analysed. The cumulative live birth rate was 52% for tubocornualanastomosis, 58% for bilateral operations and 28% for two-siteoperations. In all, 35 singleton babies were born. Of the 32operated patients who did not deliver within 2 years of surgery,21 were treated by 66 IVF cycles; 12 babies were born. The livebirth rate was 18% per cycle and 57% per patient. Combiningboth treatment methods the cumulative live birth rate was improvedup to 69% in the group of tubocornual anastomoses, up to 75%in the group of bilateral operations, and up to 57% in the groupof two-site operations. Complementary use of microsurgery andIVF and embryo transfer improves the prognosis for selectedinfertile patients with pathological proximal tubal blockage.In the absence of pregnancy, IVF and embryo transfer shouldbe commenced 1 year after surgery.     

Severe ovarian hyperstimulation syndrome and combined intrauterine and tubal pregnancy after in-vitro fertilization and embryo transfer

Ovarian hyperstimulation syndrome (OHSS) and hetero-topic pregnancyare two well recognized entities occurring after in-vitro fertilization(TVF). This is the first reported case of a severe OHSS andcoexistent heterotopic pregnancy after FVF and embryo transfer.Diagnosis of tubal pregnancy was obscured both by stimulatedovaries which prevented accurate ultrasound definition and thecoexistence of an intrauterine pregnancy which accounted forhuman chorionic gonadotropbin (HCG) concentrations and alsofor aggravation of the OHSS. The roles of transvaginal ultrasound,diagnostic laparoscopy and early paracentesis in the managementof this rare complication of assisted reproductive technologiesare discussed.     

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.