Successful management of a heterotopic Caesarean scar pregnancy: potassium chloride injection with preservation of the intrauterine gestation: case report

Caesarean scar pregnancy (CSP), in which the pregnancy is located in the scar of a previous Caesarean section, is a rare situation that carries a high risk of uterine rupture. Improved ultrasound imaging allows early diagnosis of this condition, but there is no standard management. We report the first case of CSP associated with a normal intrauterine pregnancy. Potassium chloride administered under transvaginal ultrasonographic guidance terminated cardiac activity in the CSP. The CSP resolved, and a healthy infant was delivered at 36 weeks. When the diagnosis is early and the patient asymptomatic, surgery can be avoided, the CSP can be terminated selectively and the intrauterine pregnancy thereby preserved.     

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.     

Single top quality embryo transfer as a model for prediction of early pregnancy outcome

BACKGROUND: Single embryo transfer (particularly of a top quality embryo) is an excellent model to correlate embryo quality in terms of morphological criteria to early pregnancy. We investigated whether this model could provide us with more information on what happens after implantation in the first trimester of pregnancy. METHODS: The outcome of 370 consecutive single top quality embryo transfers in patients younger than 38 years was analysed for pregnancy and first-trimester pregnancy loss (FTPL) before 13 weeks of gestation. Analysis was done on each cohort of embryos from which the transferred top quality embryo was selected. Serum HCG levels were measured on day 8 and day 12 after day 3 embryo transfer. The HCG index was calculated as the level of HCG on day 12/HCG on day 8. RESULTS: The pregnancy rate after single top quality embryo transfer was 51.9%. This was independent of the patients' age. FTPL, however, appeared to be age dependent: 15.4% for the whole group, 9% in patients younger than 30 years and 19% in patients above 30 years. The pregnancy rate was 50% in IVF cycles and 52% in ICSI cycles; FTPL was 19% in IVF cycles and 10% in ICSI cycles. Multiple regression analysis showed that these differences originated from age differences between both populations rather than from technique-related factors. An HCG level >or=45 IU/l on day 12 was predictive for ongoing pregnancy with 75.6% sensitivity and 100% specificity; an HCG index >or=3.5 similarly predicted ongoing pregnancy with 72.3% sensitivity and 100% specificity. CONCLUSIONS: These data show that embryo selection for transfer on day 3 can be used as an excellent tool for prediction of pregnancy but not for prediction of FTPL. The pregnancy rate of a single top quality embryo is not related to age, whereas FTPL is age dependent.     

Successful pregnancy after in-vitro fertilization and transmyometrial embryo transfer in a patient with congenital atresia of cervix: case report.

A case report of a patient with congenital cervical atresia diagnosed at the age of 24 years is given. The attempts to create a neocervix were unsuccessful. Since no signs of retrograde menstruation or haematometra were observed, in agreement with the patient hysterectomy was not performed. At the age of 32 years, a successful pregnancy was achieved after an in-vitro fertilization and transmyometrial embryo transfer. Due to rapidly progressing pre-eclampsia, an elective Caesarean section was performed at 32 weeks gestation. A 1610 g healthy male infant in breech presentation was born. The post-partum period was uneventful.     

Successful pregnancy by transmyometrial and transtubal embryo transfer after IVF in a patient with congenital cervical atresia who underwent uterovaginal canalization during Caesarean section: case report

Successful pregnancy in a patient with congenital cervical atresia is a great challenge for assisted reproductive techniques and reproductive medicine. We report a case of successful pregnancy by transmyometrial and transtubal embryo transfer simultaneously after in-vitro fertilization (IVF) in a 33 year-old patient with congenital cervical atresia diagnosed at the age of 18 years. The patient had experienced cyclic abdominal pain and amenorrhoea since she was 13 years old. She had had two unsuccessful attempts to create a new uterovaginal canal in another hospital. At the age of 32 years, she was referred to our unit and had a successful pregnancy after transmyometrial and transtubal embryo transfer. Caesarean section was performed at 36 weeks gestation due to progressive pre-eclampsia and gestational diabetes. A healthy male baby weighing 2812 g was safely delivered. Uterovaginal canalization with amniotic membrane for the covering of the neo-endocervical wall was performed during Caesarean section. Normal menstrual outflow and symptomatic relief have continued for 5 months after the operation. To the best of our knowledge, this is the first reported case of successful pregnancy by transmyometrial and transtubal embryo transfer as well as uterovaginal canalization performed during Caesarean section in a patient with congenital cervical atresia.     

Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers

BACKGROUND: To reduce the twin pregnancy rate, elective single embryo transfer (eSET) is increasingly implemented. Improvement of the results obtained with eSET can be achieved by better selection of the most viable embryo. This study investigated the predictive value of early cleavage (EC) as an additional parameter for selecting the embryo with the highest implantation potential by using data from SET's. METHODS: Data from 165 SET's were retrospectively evaluated. Cleavage to the 2-cell stage was determined 23-26 h after injection or 25-28 h after insemination. Selection of the embryo to be transferred was based on cell morphology and cell number on the day of transfer, not on the EC status. Additional information on the predictive value of EC on developmental potential was obtained by analysing 253 transfers with two embryos (double embryo transfer, DET) and blastocyst formation of 1160 surplus embryos. Logistic regression was used to determine the predictors of pregnancy or blastocyst development. RESULTS: A significantly higher pregnancy rate was observed after transfer of single EC embryos compared to single non-EC embryos (46 versus 18%). This result was confirmed by the significantly higher pregnancy rate after DET with two EC embryos as compared to DET with two non-EC embryos (45 versus 25%) and the blastocyst formation of EC embryos compared to non-EC embryos (66 versus 40%). Logistic regression showed that EC is an independent predictor for both pregnancy and blastocyst development in addition to cell morphology and cell number. CONCLUSIONS: In order to improve the selection of the embryo with the highest implantation potential, selection for transfer should not be based on cell number and morphology on the day of transfer alone, but also on early cleavage status.     

Ultrasound-guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers

BACKGROUND: Recent reports have suggested that ultrasound (US) guidance during embryo transfer might improve pregnancy rates. METHODS: A prospective randomized (computer-generated random table) trial was performed to compare embryo transfer under abdominal US guidance (n = 255 women) with clinical touch embryo transfer (n = 260). RESULTS: The clinical pregnancy rate was 26.3% (67/255) in the US-guided transfer group compared with 18.1% (47/260) in the clinical touch transfer group (P < 0.05). The implantation rate was 11.1% (100/903) in the US group compared with 7.5% (66/884) in the clinical touch group (P < 0.05). US-guided transfer was associated with a decrease in the difficulty of the transfers: 97% of transfers were easy in the US-guided group compared with 81% in the clinical touch group (P < 0.05). CONCLUSIONS: US-guided embryo transfer increased pregnancy and implantation rates in IVF cycles, as well as the frequency of easy transfers. It is suggested that the decrease in cervical and uterine trauma can play a role in the increase in pregnancy rates associated with US-guided transfer. It is recommended that embryo transfer should be performed under US guidance.     

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

In order to achieve a clinical pregnancy rate higher than that achieved following initial adoption of in-vitro fertilization embryo transfers, more than one embryo is transferred. This has led to a substantial increase in unwanted multiple pregnancy rates with IVF as compared with natural conception. What is therefore required is a simple, clinically useful embryo scoring system, to reflect embryo developmental potential, which will enable the selection of the optimal number of embryos to transfer in order to achieve the maximum pregnancy rate with a low incidence of high order multiple pregnancies. We believe that the Cumulative Embryo Score (CES) achieves these aims. On the day of embryo transfer the grade of each embryo transferred was multiplied by the number of blastomeres to produce a score for each embryo, and summation of the scores obtained for all the embryos transferred gave the CES. The grouped pregnancy rates obtained rose as the CES increased to maximum of 42. A continued increase in the CES above 42 did not result in any further rise in the pregnancy rate. However, an analysis of all our IVF pregnancies showed that the multiple pregnancy rate continued to rise above a CES of 42. By restricting the CES per embryo transfer to 42, 78% of triplet pregnancies and 100% of the quadruplet IVF pregnancies could have been predicted and potentially avoided.     

The impact of the embryo transfer catheter on the pregnancy rate in IVF

BACKGROUND: The aim was to assess whether the type of embryo transfer set used for embryo transfer affects the ongoing pregnancy rate in IVF. METHODS: The TDT set was compared with the K-soft 5000 in a large, prospective, randomized study. Patients were randomized moments before transfer by drawing a consecutively numbered, sealed, opaque envelope indicating the catheter to be used. RESULTS: 2059 embryo transfers in 1296 patients were analysed. The ongoing pregnancy rate was significantly higher in the K-soft group. If the first transfer of a patient (n = 1296) within this study period was analysed, the ongoing pregnancy rates were 27.1 versus 20.5% (P = 0.006). If the analysis is limited to patients that underwent their very first transfer ever (n = 607), the ongoing pregnancy rates were 30.3 versus 20.0% (P = 0.003) in favour of the K-soft. CONCLUSION: We conclude from these data that the type of embryo transfer set used for embryo transfer does affect the ongoing pregnancy rate and that the impact of the variable transfer catheter on the ongoing pregnancy rate increases when the a priori chance of pregnancy increases.     

Impact of elective single embryo transfer on the twin pregnancy rate

BACKGROUND: It is unclear how the implementation of elective single embryo transfer in clinical practice would affect clinical pregnancy and delivery rates and multiple birth rates. METHODS: This retrospective study analysed 1871 IVF/ICSI cycles carried out from 1997 to 2001 in the IVF programme of a single university infertility clinic. RESULTS: The number of elective single embryo transfers increased from 11 to 56%. At the same time the clinical pregnancy rate was relatively stable; mean 34.0% (range 28-42). The number of embryos per embryo transfer decreased from 1.8 to 1.3. The multiple pregnancy and delivery rates dropped markedly from 25 to 7.5% and from 25 to 5% respectively. CONCLUSIONS: An elective single embryo transfer programme can be adopted in daily practice that decreases the twinning rate to <10% and does not affect the overall pregnancy rate.     

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.     

Embryonic platelet-activating factor: an indicator of embryo viability

BACKGROUND: A definitive need exists to identify a biomarker of embryonic viability. Platelet-activating factor (PAF) production by human embryos is related to pregnancy potential. METHODS: Conditioned embryo culture media were obtained following conventional IVF on day 3, with PAF levels and pregnancy outcomes correlated. RESULTS: Overall pregnancy rate was 68% (17/25) with a mean of 84.1 (+/- 8.5) pmol/l/embryo PAF level. PAF levels ranged from a 216.4 pmol/l/embryo (pregnant) to a 3.7 pmol/l/embryo (not pregnant). There was a significant difference (P < 0.05) in PAF content between pregnant (92.1 +/- 9.5 pmol/l/embryo) and non-pregnant groups (52.5 +/- 16.6 pmol/l/embryo). Patients were categorized into three groups based upon PAF levels: low (< or= 5 pmol/l/embryo); medium (51-100 pmol/l/embryo) and high (>100 pmol/l/embryo). The low (60%) group had a significantly (P < 0.05) lower pregnancy rate than either the medium (85%) or high (89%) groups. A receiver-operator characteristic curve predicted a cut-off limit of 45 pmol/l/embryo for PAF content in human embryo conditioned culture media. CONCLUSIONS: The data demonstrate a correlation between PAF levels in human embryo conditioned culture media and pregnancy outcome. Additionally, as embryonic PAF levels increase so does the corresponding pregnancy rate. Therefore, PAF may be used as an indicator of embryo viability and for predicting pregnancy outcome.     

Impact of patients' choice for single embryo transfer of a top quality embryo versus double embryo transfer in the first IVF/ICSI cycle

BACKGROUND: The aim of this study was to evaluate the impact of transferring a single top quality embryo in the first IVF/ICSI cycle of patients <38 years old who chose to have one or two embryos transferred. METHODS: A total of 262 patients participated in the study, and 243 transfers were performed: 156 (64%) patients chose the transfer of a single top quality embryo, if available, and two non-top quality embryos if not available; 87 (36%) patients chose to have a double embryo transfer regardless of embryo quality. RESULTS: In the first group an ongoing pregnancy rate of 40% (63/156) with a twin pregnancy rate of 2% (1/63) was achieved. In the second group the ongoing pregnancy rate was 44% (38/87) with 26% (10/38) twin pregnancies. In the patient group with only one embryo transferred, irrespective of the patient's choice, the ongoing pregnancy rate was 43% (54/127) with no twin pregnancies. For the study population as a whole, the ongoing pregnancy rate was 42% (101/243) with 11% (11/101) twins. CONCLUSION: We conclude that the introduction of single embryo transfer in the first IVF/ICSI cycle is highly acceptable in women <38 years old.     

Pregnancy: Intramural pregnancy following difficult embryo transfer

We report an intramural pregnancy following a difficult embryotransfer in a 31 year-old woman, having in-vitro fertilizationand embryo transfer for tubal factor infertility. The creationof a ‘false passage’ at a previous instrumentationof the cervix may be implicated in the ectopic placement ofembryos     

Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth.

To avoid multiple pregnancies without compromising pregnancy rates (PR) is a challenge in assisted reproduction. We have compared pregnancy results among 74 elective one-embryo transfers (group 2) and 94 transfers where only one embryo was available (group 1). All the fresh embryo cycles during 1997 in two clinics in Helsinki were analysed, and cumulative PR among these couples after frozen-thawed embryo transfers up to June 1998 were counted. In group 2, where at least two embryos were available for transfer, and only one was transferred on day 2 or 3, the PR per embryo transfer was 29.7%. In group 1, the PR per embryo transfer was 20.2%. In group 2, the cumulative PR after frozen-thawed embryo transfers was 47.3% per oocyte retrieval. Over the same time, 742 two-embryo transfers were carried out. The PR per embryo transfer was 29.4% in these subjects, but 23.9% of these pregnancies were twins. The implantation rates, as well as the PR, were highest when the embryos were at the four- to five-cell stage on day 2 (35.8 versus 9.7% compared with the two- to three-cell stage, P < 0.001) or at the six- to eight-cell stage on day 3 (45.5%). The PR per embryo transfer was higher when a grade 1 or 2 embryo was transferred compared with a grade three embryo (34. 0 and 26.7% versus 8.8% respectively, P < 0.05). In women 35 years or younger, the PR per elective one-embryo transfer was 32.8%. The corresponding figure in women older than 35 years was 18.8%. On the basis of these results, elective one-embryo transfer can be highly recommended, at least in subjects who are younger than 35 years of age, and who have grade one or grade two embryos available for transfer.     

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.     

The use of intra-endometrial embryo transfer for increasing the pregnancy rate

It has been demonstrated previously that pregnancy can be achievedby the direct insertion of embryos into the endometrial stroma(intra-endometrial embryo transfer) of mice. In this study weevaluated whether intra-endometrial transfer resulted in a higherpregnancy rate than conventional embryo transfer. Mouse blastocysts(ICR strain), recovered on day 4 of pregnancy, were transferredinto pseudopregnant day 2, day 3 and day 4 mice of the samestrain; 1-, 2- and 8-cell embryos were also transferred intopseudopregnant day 4 mice. In intra-endometrial embryo transfer,a 27 gauge injection needle was inserted near the utero-tubaljunction into the endometrial stroma and then removed; one blastocystwas transferred into each uterine horn with a glass micropipette.Conventional transfers were performed simultaneously as controls.The pregnancy rates and embryonic viability rates were evaluated9 days after embryo transfer. Furthermore, the rates of livebirth for intra-endometrial and conventional embryo transferswere compared when blastocysts were transferred into pseudopregnantday 4 uteri by both methods. In the transfer to pseudopregnantday 2 recipients, the pregnancy and embryonic viability rateswere significantly higher (P < 0.01) in intra-endometrial[23.4 (11/47) versus 15.9% (15/94)] than in conventional embryotransfer [4.3 (2/46) versus 2.2% (2/92)]. In the transfer topseudopregnant day 3 recipients, both rates were also higher(P < 0.01) in intra-endometrial [90.9 (40/44) versus 87.5%(77/88)] than in conventional transfer [67.4 (31/46) versus64.1% (59/ 92)]. In synchronous transfer to pseudopregnant day4 recipients, there was no difference between methods in thepregnancy rate [conventional, 48.9% (24/49); intraendometrial,50.9% (29/57)] and the embryonic viability rate [conventional,44.9% (44/98); intra-endometrial, 43.0% (49/114)]. In the transferof 1-, 2- and 8-cell embryos into pseudopregnant day 4 mice,pregnancy and embryonic viability rates were very low in bothtransfer methods. Intra-endometrial transfer produced normalliving offspring at a similar rate to conventional transfer.These results reveal that intra-endometrial transfer increasespregnancy and embryonic viability rates in asynchronous embryotransfer in mice, especially when the duration of pseudopregnancyin the recipients was less than the age of the transferred embryos.     

Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre

BACKGROUND: Our aim was to supplement the mostly individual case reports on the rarely occurring and life-threatening condition of ectopic pregnancy developing in a Caesarean section scar. METHODS AND RESULTS: Eight of all the patients treated in our department between 1995 and 2002 had been diagnosed for ectopic pregnancy that developed in a Caesarean section scar. They comprised this case series group. Four of them underwent methotrexate treatment; one had expectant management, one transcervical aspiration of the gestational sac and two by open surgery. All the non-surgically treated women had an uneventful outcome. One underwent a term Caesarean hysterectomy and the other first trimester hysterotomy and excision of the pregnancy located in the scarred uterus. Analysis of all these women's obstetric history revealed that five of them (63%) had been previously operated because of breech presentation, one had a cervical pregnancy and one had placenta previa. Four of them (50%) had multiple (> or = 2) Caesarean sections. CONCLUSIONS: The women at risk for pregnancy in a Caesarean section scar appear to be those with a history of placental pathology, ectopic pregnancy, multiple Caesarean sections and Caesarean breech delivery. Heightened awareness of this possibility and early diagnosis by means of transvaginal sonography can improve outcome and minimize the need for emergency extended surgery.     

Single embryo transfer: a mini-review

This paper provides a concise review of single embryo transfer (SET) in cycles using fresh embryos as well as in cycles using frozen-thawed embryos. Relevant studies were identified by a computerized search in PubMed for the period 1995-2004. The pregnancy rates, delivery rates and multiple pregnancy/birth rates were evaluated after fresh or frozen embryo transfer as well as cumulative delivery rates after fresh and frozen SET. The results of four randomized controlled trials (RCT) and seven observational studies using fresh embryo transfers are analysed. No RCT with SET in freezing-thawing cycles was identified, while one observational study was identified. The effects of a change in the rules from the National Board of Health and Welfare in Sweden in 2003 regarding the implementation of SET in Sweden are summarized.     

First polar body morphology before ICSI is not related to embryo quality or pregnancy rate

BACKGROUND: The aim of this study was to analyse the relationship between the first polar body (1st PB) morphology and the fertilization rate, cleavage rate, embryo quality, pregnancy and implantation rate. METHODS: This was a retrospective study on 167 consecutive cycles undergoing assisted reproduction with ICSI. The 1st PB morphology was evaluated at the moment of ICSI in the 596 injected oocytes and it was coded as intact or fragmented. The fertilization rate, cleavage rate, embryo quality (three grades), pregnancy rate, implantation rate and the time elapsed between oocyte retrieval and ICSI were evaluated. The 1st PB morphology was checked twice (denudation and ICSI) in a random sample of 180 oocytes in order to verify the effect of the in vitro culture. RESULTS: No significant relationship was found between the 1st PB morphology and the fertilization rate (P=0.703), cleavage rate (P=0.055), embryo quality (P=0.673), pregnancy rate (P=0.201) and implantation rate (P=0.511). A significant positive relationship (P=0.006) was found between the frequency of the 1st PB fragmentation and the time elapsed between denudation and ICSI. The pregnancy rate was significantly higher (P=0.008) when oocytes were injected between 5 and 7 h after retrieval rather than earlier or later. CONCLUSIONS: Our data suggest that the embryo quality, pregnancy rate and implantation rate are not related to the 1st PB fragmentation. The time which elapses between the oocyte retrieval and ICSI should be maintained at approximately 6 h in order to obtain optimal results.