Cancer and male infertility: Gamete intra-Fallopian transfer or in-vitro fertilization after failed ovarian stimulation and intrauterine insemination in unexplained infertility?

A prospective randomized study was designed to compare gameteintra-Fallopian transfer (GIFT) and in-vitro fertilization (IVF)and embryo transfer in the treatment of couples who have failedto conceive after at least three cycles of ovarian stimulationand intrauterine insemination (IUI). A total of 69 couples withprimary unexplained infertility of at least 2 years' durationplus at least three failed cycles of ovarian stimulation andIUI were randomly allocated to either GIFT or IVF/embryo transfer.The clinical pregnancy rate was 34% after GIFT treatment and50% after IVF/embryo transfer. This difference was not statisticallysignificant. The twin rate in the IVF/embryo transfer groupwas higher than in the GIFT group (53 versus 17%, P = 0.005).We conclude that patients with unexplained infertility and failedovarian stimulation and IUI can still achieve encouraging pregnancyrates with IVF/embryo transfer or GIFT. Since IVF/embryo transferis the least invasive of the two procedures and may yield diagnosticinformation, we would favour this therapy; however, the numberof embryos transferred should be reduced to two to reduce therisk of twin pregnancy.     

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.     

CASE REPORT: Diethylstilbestrol-induced Mullerian abnormalities, septate uterus, genital tuberculosis and twin pregnancy with term delivery after in-vitro fertilization

We report a case of a twin pregnancy at term obtained afterfive multiple embryo transfers in a patient who presented diethylstilbestrol(DES)-associated cervical and uterine structural abnormalities,a septate uterus and bilateral tuberculous salpingitis. Thesuitability of in-vitro fertiliza tion/embryo transfer in DES-exposedwomen is discussed.     

eSET irrespective of the availability of a good-quality embryo in the first cycle only is not effective in reducing overall twin pregnancy rates

INTRODUCTION: In several clinics, elective single-embryo transfer (eSET) is applied in a selected group of patients based on age and the availability of a good-quality embryo. Whether or not eSET can be applied irrespective of the presence of a good-quality embryo in the first cycle, to further reduce the twin pregnancy rate, remains to be elucidated. METHODS: In patients <38 years two transfer strategies were compared, which differed in the first cycle only: group A (n = 141) received eSET irrespective of the availability of a good-quality embryo, and group B (n = 174) received eSET when a good-quality embryo was available while otherwise they received double embryo transfer (DET; referred to as eSET/DET transfer policy). In any subsequent cycle, in both groups the eSET/DET transfer policy was applied. RESULTS: After completion of their IVF treatment (including a maximum of three fresh cycles and the transfer of frozen-thawed embryos), comparable cumulative live birth rates (62.4% in group A and 62.6% in group B) and twin pregnancy rates (10.1 versus 13.4%) were found. However, patients in group A required significantly more fresh (2.0 versus 1.8) and frozen (0.8 versus 0.5) cycles. CONCLUSIONS: The transfer of one embryo in the first cycle, irrespective of the availability of a good-quality embryo, in all patients <38 years, is not an effective transfer policy for reducing the overall twin pregnancy rate.     

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.     

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.     

Pregnancy: Ectopic pregnancy after in-vitro fertilization is characterized by delayed implantation but a normal increase of serum human chorionic gonadotrophin and its subunits

We studied the dynamics of serum human chorionic gonadotrophin(HCG) and its free (HCG) and (HCGP) subunits in 49 early pregnanciesachieved by in-vitro fertilization (IVF) and embryo transfer.Of the 49 early pregnancies, nine were normal singleton pregnancies,11 were twin pregnancies, 11 were ectopic, eight ended in aclinical (spontaneous) abortion and 10 ended in a preclinicalabortion. The HCG, HCGa and HCGP concentrations in serum weremeasured on days 12, 19 and 26 after embryo transfer. Most ectopicpregnancies could be distinguished from singleton (and twin)pregnancies on the basis of low HCG concentrations by 12 daysafter embryo transfer, but clinical abortions could not be distinguishedfrom singleton pregnancies. In general, the measurement of HCGaand HCG and the molar ratios of the various forms provided onlymarginal additional value to that obtained from HCG, but ondays 19 and 26 after embryo transfer HCGa was the most sensitiveindicator of a normal pregnancy after IVF and embryo transfer.We conclude that in ectopic pregnancies the concentrations ofHCG, HCGa and HCGP increase as expected but 1.5 days later thanin normal pregnancies. This appears to be the result of a delayin implantation.     

In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial

BACKGROUND: Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme. However, the reduced overall multiple pregnancy rate (PR) is still unacceptably high. Therefore, a randomized controlled trial (RCT) was conducted comparing eSET and double embryo transfer (DET) in an unselected group of patients (i.e. irrespective of the woman's age or embryo quality). METHODS: Consenting unselected patients were randomized between eSET (RCT-eSET) (n = 154) or DET (RCT-DET) (n = 154). Randomization was performed just prior to the first embryo transfer, provided that at least two 2PN zygotes were available. Non-participants received our standard transfer policy [SP-eSET in a selected group of patients (n = 100), otherwise SP-DET (n = 122)]. RESULTS: The ongoing PR after RCT-eSET was significantly lower as compared with RCT-DET (21.4 versus 40.3%) and the twin PR was reduced from 21.0% after RCT-DET to 0% after RCT-eSET. The ongoing PRs after SP-eSET and SP-DET did not differ significantly (33.0 versus 30.3%), with an overall twin PR of 12.9%. CONCLUSION: To avoid twin pregnancies resulting from an IVF treatment, eSET should be applied in all patients. The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients. The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9%.     

Andrology: Epididymal sperm aspiration and use of donor spermatozoa when necessary for in-vitro fertilization, and vasoepididymostomy: an acceptable combination in the treatment of obstructive azoospermia

Infertility due to obstructive azoospermia in 24 men was treatedwith a combination of scrotal exploration, microsurgical spermaspiration and vasoepididymostomy, at the same operation. In-vitrofertilization (IVF) and embryo transfer were performed usingepididymal spermatozoa. Donor spermatozoa were used if no motileepididymal spermatozoa were obtained. With this combination,emotionally and economically acceptable pregnancy rates wereachieved: 24% per aspiration, 43% per embryo transfer, and 25%per couple. One twin pregnancy resulting in the birth of twohealthy female infants and one ongoing twin pregnancy were achievedwith epididymal spermatozoa; four pregnancies (one twin, twosingletons, one abortion) were achieved with donor spermatozoa.     

One versus two embryo transfer after IVF and ICSI: a randomized study

BACKGROUND: The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups. RESULTS: The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS: Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.     

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.     

Attitudes of German infertile couples towards multiple births and elective embryo transfer

BACKGROUND: In Germany, embryo screening programmes combined with elective embryo transfer are illegal, but there is controversial debate about their legalization. Studies about the attitudes of infertile couples towards multiples, elective embryo transfer and multifetal reduction may help to illuminate how this law shapes patient choices. METHODS: A survey of 265 German infertile couples was conducted. Different logistic regression analyses were performed to assess independent factors associated with the parity for multiple births, approval for elective embryo transfer and multifetal reduction. RESULTS: Despite prior information about the risk of multiple births, 81% of respondents saw no risk in twin pregnancies and a sizable minority saw no risk even in triplet pregnancies. Eighty-nine percent of the respondents rated a twin pregnancy as desirable, whereas 35% rated a triplet birth as desirable. When presented with a choice of having multiple births versus having no biological children, 99% of the respondents endorsed twins, 84% triplets and 58% quadruplets. Seventy-four percent of the respondents approve of legalizing embryo screening programmes to select a good-quality embryo combined with elective embryo transfer. Ninety-two percent of the respondents rejected fetal reduction of twins. CONCLUSIONS: German infertile couples might conceivably be more willing to accept elective embryo transfer if screening for viable embryos was permitted.     

What is the most relevant standard of success in assisted reproduction?: no single outcome measure is satisfactory when evaluating success in assisted reproduction; both twin births and singleton births should be counted as successes

The 2002 recommendation of the consensus meeting of the European Society of Human Reproduction and Embryology (ESHRE) that the outcome measure of assisted reproductive technology (ART) and non-ART should be 'singleton live birth rate' could profoundly effect the ability of infertility patients to become pregnant. We reviewed published reports and new data concerning elective single embryo transfer (eSET) vs. double embryo transfer (DET) and the outcome of twin pregnancies in the United States, as well as recommendations of other Societies concerning number of embryos to transfer and methods used to measure ART success. We found that no single outcome measure of ART is ideal. Mandatory eSET would result in 42%-70% fewer births compared to DET. Infertility treatments account for only 12% of all twin pregnancies and 4% of all premature births in the United States. Twin and singleton births due to ART do not occur earlier than spontaneously conceived twins and singletons unless they started as triplet and higher order pregnancies. Multiple outcome measures are necessary when evaluating ART success. Twin as well as singleton births should be counted as ART successes. The essential aim of infertility treatment should be a healthy low order (singleton or twin) birth.     

A randomized clinical trial comparing recombinant hyaluronan/recombinant albumin versus human tubal fluid for cleavage stage embryo transfer in patients with multiple IVF-embryo transfer failure

BACKGROUND: We aimed to examine the efficacy of using an embryo transfer medium enriched with hyaluronan (HA) to improve implantation in a selected group of patients aged <43 years with repeated (>4) implantation failures after IVF-embryo transfer. METHODS: About 101 patients, meeting our selection criteria, were randomly allocated to undergo embryo transfer either using our routine embryo transfer medium without HA (control group) or a HA enriched commercial embryo transfer medium (study group). The primary outcome was clinical pregnancy rate. RESULTS: After a similar treatment protocol, the ovarian hormonal response, the mean number of ova retrieved and injected per patient, fertilization and cleavage rates and mean embryo quality were comparable between the study and control groups. Although a similar number of embryos was transferred in both groups (3.1 +/- 0.7 versus 2.9 +/- 0.6, mean +/- SD), a significantly higher implantation rate (16.3% versus 4.8%, P = 0.002) and clinical pregnancy rate (35.2% versus 10.0%, P = 0.004) and delivered or ongoing pregnancy rate (31.3% versus 4.0%, P = 0.0005) were observed in the study group. When mean implantation rate per patient was calculated, the difference between the study (0.148 +/- 0.23) and control (0.04 +/- 0.13) group was significant (P = 0.003). CONCLUSIONS: In this selected group of patients after multiple IVF-embryo transfer failures, the use of HA enriched embryo transfer medium is beneficial.     

IVF/ICSI twin pregnancies: risks and prevention

Since the 1970s, the national twin birth rates have been increasing worldwide. Apart from the increasing childbearing age, the main cause is the use of assisted reproductive technologies (ART). To explore the overall consequences of dual embryo transfer (DET), the literature has been reviewed systematically regarding short- and long-term outcomes of IVF/ICSI twin pregnancies i.e. pregnancy complications, maternal risks, obstetric outcome and long-term morbidity including neurological sequelae, cognitive development and family implications. Another consequence of DET is vanishing twins, which seems to be a possible cause of adverse outcome in IVF singletons. The sparse literature on vanishing twins in IVF pregnancies and the influence on the surviving co-twin were also addressed. Finally, to determine the effects of implementing elective single embryo transfer (eSET), trials concerning eSET versus DET were analysed. In the light of the steadily increasing twin birth rates and the findings in this overview, where IVF/ICSI twins carry adverse outcome, it should be emphasized that the major obstacle in IVF remains the high twin birth rate. Furthermore vanishing twins account for another hazard of DET. These problems can be resolved by implementing eSET, diminishing the twin birth rate without affecting the overall goal of achieving a healthy infant.     

Is a prolonged bed rest following embryo transfer useful?

A total of 182 infertile patients undergoing in-vitro fertilization (IVF)-embryo transfer were randomly assigned into two groups. Eighty- seven patients (group A) underwent 97 treatment cycles and had 87 embryo transfer procedures followed by a 24 h period of bed rest. Ninety-five patients (group B) underwent 102 treatment cycles and had 93 embryo transfer followed by a 20 min period of bed rest. There were no statistically significant differences seen between the groups with respect to age, duration and causes of infertility and number of previous fertility treatments. The clinical and biological procedures were identical in both groups, the only difference being the length of bed rest. There were 21 pregnancies in group A (pregnancy rate per embryo transfer: 24.1%) while in group B there were 22 (pregnancy rate per embryo transfer: 23.6%). There were four spontaneous miscarriages (19%) and three twin pregnancies (14.2%) in group A, while in group B there were four spontaneous miscarriages (18.1%) and three twin pregnancies (13.6%). None of these values was statistically significant (P > 0.05). This study shows that a 24 h period of bed rest following embryo transfer is not associated with a better outcome of the IVF- embryo transfer when compared with a 20 min rest period. Prolonged bed rest does not appear to influence the implantation rate after IVF- embryo transfer.      

Avoiding multiple pregnancies in ART: a plea for single embryo transfer

It has been generally accepted that triplets after IVF/intracytoplasmic sperm injection (ICSI) can and should be avoided by adopting a standard strategy of replacing no more than two embryos. However, there is an increasing awareness of the risks and costs and of the epidemic size of twin pregnancies after IVF/ICSI. This has resulted in efforts to replace no more than one embryo. However, this approach has been hampered by our relative inability to identify embryos with a very high implantation potential. To identify such embryos, a number of strategies are being considered, both at the two pronuclear (2PN), early cleavage and the blastocyst stages. At the 2PN stage, the polarity characteristics of the nucleoli have been shown to be correlated with a high implantation rate. Similarly, the morphological characteristics at day 2 and 3 have been used to describe top quality embryos in approximately 75% of all IVF/ICSI cycles. Blastocyst culture has resulted in very high implantation rates in the hands of some authors. No approach has shown its superiority at present, but initial experience with single embryo transfer (SET) at the early cleavage stage by Scandinavian and Belgian groups shows that an ongoing pregnancy rate of 35% and more can be achieved. Proper identification of patients at risk of a twin pregnancy after double embryo transfer is equally important. It is clear that mainly young patients (aged <34 years) during their first, perhaps first two, IVF/ICSI cycles constitute the main population at risk (responsible for >80% of all twins) and are the main target group for twin prevention by SET of a top quality embryo at whatever stage. Therefore, in our opinion, although a further fine-tuning of both embryo and patient characteristics relating to a high risk for (twin) pregnancy is desirable, SET should be introduced carefully and progressively in each IVF/ICSI programme from now on. Correct counselling is very important and both public and private insurers will have to join in the discussion.     

Is twin pregnancy necessarily an adverse outcome of assisted reproductive technologies?

Sir, We want to thank van Wely et al. (2006) for daring to publishwhat many physicians believe privately, but are unwilling toexpress publicly, concerning twin pregnancy. Single embryo transfer,currently dominating medical journals (Gleicher, 2006),     

Hydatidiform moles associated with multiple gestations after assisted reproduction: diagnosis by analysis of DNA fingerprint

In spite of the widespread use of assisted reproductive technology, there have been, to our knowledge, only two reported cases of molar pregnancies after gamete intra-Fallopian transfer and five reported cases after in-vitro fertilization and embryo transfer. We report here a case of a complete hydatidiform mole in a twin pregnancy after gamete intra-Fallopian transfer, as well as a case of a complete hydatidiform mole in a triplet pregnancy after in-vitro fertilization and embryo transfer. The genetic constitution of each conceptus was determined by examination of the restriction fragment length polymorphism of the DNA with four different single-locus probes. This analysis revealed that both hydatidiform moles were of androgenetic origin and probably of monospermic origin. Moreover, the analysis confirmed that the pregnancies were dizygotic and trizygotic pregnancies respectively. The diagnostic utility of the analysis of DNA polymorphism is discussed in cases of a molar pregnancy with coexisting fetuses.      

Cost-effectiveness analysis of in-vitro fertilization: estimated costs per successful pregnancy after transfer of one or two embryos

Standard protocols for in-vitro fertilization (IVF) include transfer of two or three embryos. Not surprisingly, the rate of twin pregnancy after IVF is high (about 24% of all pregnancies). Routine transfer of one, rather than two, embryos would be expected to result in a much lower rate of twin pregnancies at the cost of a lower take-home baby rate. The aim of this study was to compare hypothetical costs to society incurred by pregnancies achieved with IVF protocols based on the transfer of one or two embryos. We compared actual (for two-embryo transfers) and hypothetical (for one-embryo transfers) take-home baby rates; risks of twin pregnancies; and costs of sick leave and hospitalization during pregnancy, deliveries, neonatal intensive care, and handicap care after transfer of one or two embryos. The study showed that even when more treatments might be needed to achieve similar baby take-home rates after transfer of one compared with two embryos, the lower twin pregnancy rate of the former approach caused it to be more cost-efficient than the latter. In conclusion, IVF costs are the sum of fertilization treatment costs and the costs for health care of the pregnant women and their offspring. Considering the association of the latter costs with numbers of embryos transferred, studies of one- embryo transfer protocols are urgently needed.