Successful non-surgical management of a heterotopic abdominal pregnancy following embryo transfer with cryopreserved-thawed embryos.

Heterotopic pregnancy is an increasingly common complication of assisted reproductive technology. Abdominal pregnancy is a rare and life-threatening form of ectopic pregnancy that can present as the extrauterine portion of a heterotopic pregnancy. We present the case of a cryopreserved-thawed embryo transfer that resulted in a simultaneous intrauterine and abdominal pregnancy first recognized at 10 weeks gestation. Ultrasound-guided transvaginal injection of potassium chloride into the abdominal pregnancy resulted in asystole and spontaneous resorption of the ectopic fetus, while the intrauterine pregnancy continued and resulted in a liveborn vaginal delivery at full term. Selective embryo reduction using a non-surgical approach in a haemodynamically stable patient can therefore be considered in the management of heterotopic abdominal pregnancy if diagnosed relatively early.     

Multiple pregnancy after in-vitro fertilization and embryo transfer: report of a quadruplet pregnancy and delivery

The first baby from in-vitro fertilization (IVF) was born in England in 1978 as a result of retrieval of a single preovulatory oocyte in the course of a natural cycle (Steptoe and Edwards, 1978). At present most programmes of IVF throughout the world do not use natural cycles producing only one oocyte, but rather multiple oocyte cycles produced by clomiphene citrate (CC), human menopausal gonadotrophin (HMG), or pure follicle stimulating hormone (FSH), either separately or in combination, sequentially or concomitantly, for the induction of multiple follicular maturation.     

Pregnancy: Heterotopic abdominal pregnancy following in-vitro fertilization/embryo transfer presenting as massive lower gastrointestinal bleeding

We present a case that, as far as we know, is the first reportof lower gastrointestinal haemorrhage as a complication of heterotopicpregnancy induced by artificial reproductive technology. Theheterotopic abdominal pregnancy caused erosion of the intestinalwall and massive rectal bleeding, 8 weeks after in-vitro fertilization/embryotransfer. The source of the bleeding could not be identifieddespite comprehensive investigation including gastroscopy, ultra-sonography,sigmoidoscopy, ⁹⁹Tc (technetium) scanning and angiography. Tagged-erythrocyteisotope scanning revealed an abnormal concentration in the leftlower quadrant, compatible with active bleeding in the areaof the terminal ileum. Laparotomy disclosed a heterotopic abdominalpregnancy, causing erosion of the intestinal wall at this site.As assisted reproductive technologies become more and more commonthis rare complication of intestinal erosion should be keptin mind in cases of lower gastrointestinal bleeding.     

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.     

Prospective evaluation of simple morphological criteria for embryo selection in double embryo transfer cycles

Preventing the occurrence of high-rank multiple pregnancieswithout reducing the pregnancy rate remains a high priorityof in-vitro fertilization and embryo transfer programmes. Ourprevious study demonstrated that, if there is at least one embryowith a good morphological grade, then the transfer of two (adouble embryo transfer) instead of three embryos does not resultin a lower pregnancy rate, and that the influence of the numberof embryos transferred becomes significant only when poor-qualityembryos are transferred. This result allowed us to employ thesimple policy of systematically selecting double embryo transfercycles without affecting the pregnancy rate. Since January 1994,when patients <37 years of age had more than two embryosavailable for transfer, only two instead of three embryos weretransferred if at least one of the embryos demonstrated a goodmorphological grade. After a 1 year application of this policy,of the 147 cycles (group A) that fulfilled the above criteria,two embryos were transferred in 92 cycles, while three embryoswere transferred in the other 55 cycles. The results of thesecycles were compared to those of the control 144 cycles (groupB) in which three embryos were transferred, prior to the applicationof this policy. The on-going pregnancy rates and the incidenceof multiple and triplet pregnancies were 24% and 28%, 22% and23%, and 2% and 9% in groups A and B respectively. The rateswere not significantly different. In conclusion, although ourprospective trial demonstrated a tendency of decreasing pregnancyrate and an invariable incidence of multiple pregnancies, thevery low occurrence of triplets during this period indicatedthat this policy provided a practical compromise between achievinga high pregnancy rate and an acceptable incidence of tripletpregnancies.     

Broad ligament twin pregnancy following in-vitro fertilization

We report the first case of an ectopic twin pregnancy in the broad ligament following in-vitro fertilization and embryo transfer in a patient with a previous ipsilateral (left) salpingo-oophorectomy. The previous surgery was for endometriosis. We discuss the possible contribution of the embryo transfer technique, limitations of preventive measures and importance of transvaginal ultrasound in establishing the diagnosis.     

Do patients need to remain in bed following embryo transfer? The Birmingham experience of 103 in-vitro fertilization cycles with no bed rest following embryo transfer

Since the early days of human in-vitro fertilization and embryotransfer, rest in bed for hours immediately following the transferhas been advocated and widely practised. However, there is noscientific validation for this practice which is both time-consumingfor the patient and increases space occupancy in the hospitalor clinic. We report here on a study of 103 in-vitro fertilizationcycles with no bed rest in hospital following the embryo transfer.The mean number of embryos transferred was 2.7 (range 1–3)and the clinical pregnancy rate per embryo transfer procedurewas 40%. These results suggest that bed rest is not necessaryfollowing embryo transfer.     

Infertility: Assessments of embryo transfer after in-vitro fertilization: effects of glyceryl trinitrate

The role of embryo transfer and its associated difficultieson the outcome of human in-vitro fertilization (IVF) were examinedusing a standardized procedure and a scoring system (embryotransfer scores 1–5). This system was used to assess anyeffects of the smooth muscle relaxant glyceryl trinitrate (GTN)on embryo transfer. Patients (n = 120) were randomized in adouble-blind manner at their first embryo transfer to receivesublingual GTN or placebo before the transfer. Retrospectiveanalysis showed that higher pregnancy rates were associatedwith uncomplicated transfers (score 1; P < 0.01). The outcomemeasures included pregnancy rate, total time of cervical manipulation(embryo transfer time) and embryo transfer score. All pregnancieshad a transfer score of 1 or 2, but no recorded parameter differentiatedbetween pregnant or non-pregnant cycles, and GTN had no significanteffect on any parameter.     

Elective single embryo transfer: the value of cryopreservation

In-vitro fertilization is associated with a high rate of multiple pregnancies, a consequence of the number of embryos transferred. There is a challenge in avoiding even twin pregnancies in assisted reproduction, and this can be accomplished with elective single embryo transfer and a good cryopreservation programme. In our follow-up study, we analysed all our elective single embryo transfers during 1998-1999. In all these cycles at least one embryo was frozen. A total of 127 elective single embryo transfers were performed with a clinical pregnancy rate of 38.6%. The highest implantation rate was obtained with four-cell embryos with <10% fragmentation (39.8%). Thirty-four patients have delivered (26.8%), one of these being a monozygotic pregnancy. In total 129 frozen-thawed cycles have been achieved in 83 patients. One frozen-thawed embryo has been transferred in 46 cycles with a clinical pregnancy rate of 17.4%, and two embryos have been transferred in 83 cycles, with a clinical pregnancy rate of 37.3%. Up until now, 66 of 125 patients in our single embryo transfer programme have delivered or have on-going pregnancies, and 77 still have embryos frozen. The cumulative delivery rate per oocyte retrieval is 52.8% and the twin rate 7.6%. We conclude that elective single embryo transfer with a good cryopreservation programme results in very acceptable pregnancy rates with a low risk of twins. This is a cost-effective practice that substantially reduces all risks associated with multiple pregnancies and lowers the cost per delivery.     

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.     

Fertilization and early embryology: The applicability of the cumulative embryo score system for embryo selection and quality control in an in-vitro fertilization/embryo transfer programme

The cumulative embryo score system involves three aspects ofrelevance in pregnancy achievement during in-vitro fertilization(IVF) and embryo transfer: cleavage rates, morphological qualitiesand the number of embryos transferred. The scores of 602 IVF/embryotransfer trials were calculated and analysed to determine thesystem's relationship to pregnancy rate, pregnancy outcome andthe incidence of twin and triplet pregnancies. The system wasalso applied to cycles where endotoxins were either presentin or absent from culture medium, in order to evaluate its validityin quality control analyses. Pregnancy rates were found to increasefrom 4%, with scores between 1 and 10, to 35% in the 41–50group. The score of 20 was the criterion for separating patientsinto poor and good pregnancy prognosis groups (P = 0.00001).Biochemical abortions occurred more frequently with scores <20(P = 0.00978), but a similar relationship was not found in clinicalabortion rates (P = 0.62206). Birth rates below and above ascore of 20 (2.8 and 19.2%, respectively) differed significantly(P = 0.0005). The scores of twins overlapped extensively withthose of singleton births, but those of all triplets were >40. The system did not reflect a correlation between embryoquality and the presence of endotoxins in culture medium.     

Immunology: Mock embryo transfer with a full bladder immediately before the real transfer for in-vitro fertilization treatment: the Birmingham experience of 113 cases

The technique of embryo transfer can have a great impact onthe outcome of in-vitro fertilization (IVF) treatment. Transcervicalembryo transfer is a blind procedure and difficulty can unexpectedlyarise. Many IVF programmes therefore perform a ‘mock’embryo transfer prior to the treatment cycle to determine themost suitable catheter and technique for transfer. This, however,adds an extra separate procedure with time and cost implications.Moreover, as the uterus is mobile, its direction may vary onthe day of the embryo transfer from what it was during the mockembryo transfer. Performing mock embryo transfer immediatelybefore the real transfer would circumvent these problems. Wereport here on 113 embryo transfer procedures where a ‘step-wise’mock embryo transfer protocol was performed with a full bladderimmediately before the embryo transfer. The number of embryostransferred (mean ± SD) was 2.6 ± 0.67, the pregnancyrate per embryo transfer was 45.1%, and the intrauterine implantationrate per embryo transferred was 20.6%.     

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.     

Comparison of two elective transfer policies of two embryos to reduce multiple pregnancies without impairing pregnancy rates.

A first elective transfer policy of two embryos based solely on embryo morphology was compared to a more restrictive policy transferring two embryos to all patients aged < 35 years with less than three previous cycles to reduce the incidence of multiple pregnancies. With a significant reduction in the number of triple transfers from 72.4 to 44.3%, the delivery rates were similar for both policies, 31 and 32.1%. However, the multiple pregnancy rates per transfer significantly decreased from 12.5 to 7.8% (P < 0.05). Of 99 pregnancies, only 24.2% were multiple including 1% of triplets compared to 40.7% multiple pregnancies including 6.7% of triplets for the first policy. Forty-eight transfers of two average embryos with the new policy were compared to 264 transfers of three average embryos with the old policy. Multiple pregnancy rates per transfer were significantly reduced by a third from 23 to 8% (P < 0.05) without a reduction of the pregnancy rates (42 and 48%). This study demonstrated that elective transfer of two embryos reduced the number of multiple pregnancies without impairing the pregnancy rates even with the transfer of average embryos.     

Colour Doppler indices of follicular blood flow as predictors of pregnancy after in-vitro fertilization and embryo transfer.

Peak systolic velocity (PSV) of individual follicles has been correlated with oocyte recovery, fertilization rate and embryo quality [in women undergoing in-vitro fertilization (IVF) and embryo transfer]. The present study assessed the role of quantitative and qualitative indices of follicular vascularity in predicting pregnancy after IVF and embryo transfer. A total of 106 women undergoing IVF treatment for infertility who were considered to be at risk of failure (>37 years of age, history of low response to gonadotrophin stimulation, or multiple failed IVF cycles) constituted the study group. PSV was measured from the three largest follicles on both the right and left ovaries on the day of human chorionic gonadotrophin (HCG) administration using an Acuson Sequoia with a 4-8 MHz transvaginal probe. The quality of follicular flow was graded from 1 to 4 according to the amount of visible colour flow around the follicle (grade 1 when one-quarter of the follicle, grade 2 when one-half, grade 3 when three-quarters, and grade 4 when the entire follicle was surrounded by colour). Clinical pregnancies resulted in 11 (10%) of the 106 high-risk women. Women who had PSV >/= 10 cm/s in at least one follicle on the day of HCG administration more often became pregnant than those with PSV <10 cm/s (P = 0.05). All pregnancies occurred in women with grade 3 or 4 follicular blood flow. Qualitative as well as quantitative measurements of follicular flow predict pregnancy after IVF and embryo transfer.     

Pregnancy: The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome

To assess the incidence of miscarriage, multiple pregnancy andoutcome of pregnancy in relation to the number of embryos transferredduring in-vitro fertilization (IVF), an analysis was performedof 1060 pregnancies conceived in a tertiary-referral IVF clinic.There was no difference in the miscarriage rate after transferof one or two embryos (37.7% and 34.6%), or after three or fourembryos (22.5% and 25.2%). The miscarriage rate was, however,higher when one or two embryos were transferred compared withthree (P < 0.01) or four embryos (P < 0.02). Of the 724ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%)twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean(±SD) ages of women with singleton, twin, triplet andquadruplet pregnancies were 32.5 (±3.8), 32.0 (±3.5),29.76 (±4.3) and 29.67 (±2.5) years respectively.The mean age of women with singleton and twin pregnancies wassimilar and both were greater than that of triplet pregnancies(P < 0.007). The overall perinatal mortality rate (PNMR)was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins80.0/1000 and for triplets 30.6/1000. All of the babies fromthe three quadruplet pregnancies survived. There were more babieslost in the twin pregnancies than any other group, althoughthis only reached significance for singletons versus twins (P< 0.00005). We conclude that the incidence of miscarriageis increased in women in whom one or two embryos are transferred.Multiple pregnancies are more likely to occur in younger womenand are associated with a significantly higher rate of perinatalmortality.     

CASE REPORT: Monozygotic triplet pregnancy following transfer of frozen-thawed embryos

We report a case of monozygotic triplet pregnancy after thetransfer of three frozen-thawed embryos. The outcome of thepregnancy was the birth of three healthy normal boys. The pregnancywas a monochorionic triamniotic triplet pregnancy. This is thefirst such case of triplets, although it seems that zygote splittingis significantly more common than normal in patients undergoingin-vitro fertilization.     

Transvaginal intratubal embryo transfer: a new treatment of male infertility

Intratubal embryo transfer is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in-vitro fertilization (IVF) is performed and embryos are transferred into the Fallopian tube transvaginally. In comparison with gamete intra-Fallopian transfer (GIFT), fertilization under in vitro conditions offers the advantage that the success of the fertilization process can be examined. Therefore, this method can give important diagnostic information, especially in cases of poor sperm quality or unexplained infertility. After fertilization in vitro and transfer into the tube, embryonic development occurs in the physiological milieu of the oviduct. Transvaginal intratubal embryo transfer was performed in 95 patients with male factor infertility. In 29 cases (31%), a pregnancy was achieved. One abortion, but no ectopic pregnancy was observed. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility.     

Ovarian hyperstimulation syndrome and benign intracranial hypertension in pregnancy after in-vitro fertilization and embryo transfer: case report.

Ovarian hyperstimulation syndrome (OHSS) is a dangerous and sometimes life-threatening complication of ovulation induction with exogenous gonadotrophins. While many complications of severe OHSS are recognized we have only identified one review detailing neurological problems. This report concerns a 32-year-old patient with bilateral tubal blockage who achieved her first pregnancy following in-vitro fertilization (IVF) and embryo transfer. Shortly after embryo transfer she developed clinical signs of moderate OHSS with symptoms which were later diagnosed as benign intracranial hypertension (BIH). The BIH was treated effectively using repeated lumbar puncture and diuretics. Spontaneous labour and delivery occurred at 40 weeks' gestation. There was no neurological sequel and no recurrence of the BIH 2 years after the pregnancy. The possible link between OHSS and BIH is discussed as well as the risks of further pregnancy.     

Implantation: Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers

The purpose of this study was to devise an embryo score to predictthe likelihood of successful implantation after in-vitro fertilization(IVF). Unlike most studies dealing with the influence of embryostage and morphology on pregnancy, our study was based on singlerather than multiple embryo transfers. A total of 957 singleembryo transfers were carried out. No delivery was obtainedafter any of the 99 transfers using 1-cell embryos or embryosobtained after delayed fertilization. In the remaining 858 transfers,the embryos had cleaved. Higher pregnancy rates were obtainedwith embryos displaying no irregular cells (11.7 versus 6.9%;P < 0.01) and embryos displaying no fragmentation (11.5 versus8.1%; P < 0.05). The 4-cell embryos implanted 2-fold moreoften than embryos with more or less cells (15.6 versus 7.4%;P < 0.01). Based on these observations, we devised a 4-pointembryo score in which embryos are assigned 1 point each if they(i) are cleaved, (ii) present no fragmentation, (iii) displayno irregularities, and (iv) have four cells. Both pregnancyrate and take home baby rate were significantly correlated withembryo score. Each point of this score corresponds to a 4% increasein pregnancy rate. Interestingly, pregnancy rate was significantlylower in women aged >38 years (8.2 versus 11.4%; P < 0.05),even though embryo quality was similar regardless of age. Singleembryo transfer allowed us to define a simple and useful embryoscore to choose the best embryo for transfer to optimize IVFand embryo transfer outcome. The use of this embryo score coulddecrease multiple pregnancies after multiple embryo transfers.