Characterization of a top quality embryo, a step towards single-embryo transfer.

In most in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programmes approximately one ongoing pregnancy in three is multiple. The need to characterize embryos with optimal implantation potential is obvious. We retrospectively examined all of 23 double transfers resulting in ongoing twins, occurring between January 1, 1996 and May 19, 1997. Characteristics of these top quality embryos were absence of multinucleated blastomeres, four or five blastomeres on day 2, seven or more cells on day 3, and 2 embryos, 11/31 (35%) were multiple. We applied our top quality criteria to the 221 double transfers: 106 transfers with two top embryos resulted in 65 (63%) ongoing pregnancies with 37 (57%) twins, 65 transfers with one top embryo in 38 (58%) ongoing pregnancies with eight (21%) twins. In the group without top embryos, 12/52 (23%) ongoing singletons occurred, with no twins. The corresponding ongoing implantation rates were 49, 35 and 12%. This analysis suggests that single embryo transfer with an acceptable pregnancy rate might be considered if a top quality embryo is available.     

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.     

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.     

Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles

BACKGROUND: Single embryo transfer (SET) after IVF/ICSI has been shown to result in an acceptable pregnancy rate in selected subjects. In our unit, SET is routinely carried out among women under the age of 36 in the first or second treatment cycle when a top-quality embryo is available. In order to define further the selection criteria for SET, we have analysed the outcome of elective SET (eSET), including the cumulative pregnancy rate after frozen embryo transfers, performed in the years 2000-2002 in the Oulu Fertility Center. METHODS: During the study period, a total of 1271 transfers were performed, and in 468 cycles SET (39% of all transfers) was carried out. Of the SET cycles, in 308 cases a top-quality embryo was transferred on day 2 and extra embryos were frozen. Of these eSET cycles, ICSI was carried out in 87 cycles (28%). RESULTS: The overall clinical pregnancy rate per transfer was 34.7% in the eSET cycles. In the eSET ICSI cycles, the clinical pregnancy rate was significantly higher than in the corresponding IVF cycles (50.6 versus 28.5%, P < 0.001). The cumulative pregnancy rate per patient after fresh and frozen embryo transfers was also significantly higher after ICSI (71.2 versus 53.4%, P < 0.01). CONCLUSIONS: A high cumulative pregnancy rate per oocyte retrieval can be achieved after eSET in daily clinical practice. The implantation rate of fresh top-quality embryos in the ICSI cycles was significantly higher than in the IVF cycles, possibly due to more successful selection of the embryo for embryo transfer on day 2 after ICSI. In addition, our data suggest that embryo quality is a more important determinant of outcome than the age of the woman.     

Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme

BACKGROUND: Data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. METHODS AND RESULTS: A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. CONCLUSIONS: Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.     

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.     

Elective single embryo transfer in women aged 36-39 years

BACKGROUND: The elective single embryo transfer policy is the only effective strategy known to minimize the risk of multiple pregnancy. However, little is known about its applicability to women older than 35 years. METHODS: Analysis was carried out on 1224 fresh IVF/ICSI cycles with embryo transfer and 828 frozen embryo transfer (FET) cycles of women aged 36-39 years. In the fresh cycles, 335 elective single top quality embryo (eSET), 110 elective single non top quality embryo (nt-eSET), 194 compulsory single embryo (cSET) and 585 double embryo transfers (DET) were carried out. RESULTS: Pregnancy rate/embryo transfer (33.1 versus 29.9%) and live birth rate (26.0 versus 21.9%) in fresh cycles did not differ significantly between the eSET and the DET groups. However, women in the eSET group had a higher cumulative pregnancy rate (54.0% versus 35.0%) and a higher cumulative live birth rate (41.8% versus 26.7%, P < 0.0001) compared with those in the DET group. The cumulative multiple birth rate in the eSET group was 1.7%, whereas in the DET group it was 16.6% (P < 0.0001). CONCLUSIONS: The eSET policy can be applied also to patients aged 36-39 years, reducing the risk of multiple birth and increasing the safety of assisted reproduction technique (ART) in this age group.     

Elective single embryo transfer (eSET) policy in the first three IVF/ICSI treatment cycles

BACKGROUND: Elective single embryo transfer (eSET), applied in the first or second IVF cycle in young patients with good quality embryos, has been demonstrated to lower the twin pregnancy rate, while the overall pregnancy rate is not compromised. It is as yet unclear whether eSET could be the preferred transfer policy in all treatment cycles, or that it should be restricted to the first or first two cycles. METHODS: eSET policy (when two or more embryos were available, at least one of them being of good quality) was offered to patients younger than 38 years in the first three treatment cycles. Retrospectively, treatment cycle outcome was studied. RESULTS: In 326 patients, 586 treatment cycles were performed (326 first, 168 second and 92 third treatment cycles). In 65 cycles (11%), eSET could not be applied because there was either no fertilization, or only one embryo available. In the remaining 521 cycles, eSET was performed in 111 cycles (19%), while in 410 cycles, no good quality embryo was available resulting in the transfer of two embryos (double embryo transfer, DET). No significant differences in ongoing pregnancy rates after transfer of fresh embryos were observed between eSET and DET in the first (both 33%), second (36 and 23%, respectively) and third treatment cycles (20 and 24%, respectively). In significantly more eSET cycles compared to DET cycles, could embryos be frozen. This resulted in a significantly higher cumulative pregnancy rate after eSET compared to DET. CONCLUSIONS: In patients younger than 38 years with at least one top quality embryo, eSET can be the transfer policy of choice in at least the first three treatment cycles, since the pregnancy rates obtained in each treatment cycle are comparable to those after DET.     

Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome

BACKGROUND: Frozen embryo transfers are characterized by impaired pregnancy outcome and increased incidence of pregnancy loss as compared with fresh IVF/ICSI embryo transfers. In this study, we performed a retrospective analysis of clinical and embryological factors that potentially influence the outcome of frozen embryo transfer. METHODS: We reviewed the outcome of 1242 frozen embryo transfers with respect to the age of the woman, the method of fertilization, embryo quality before and after freezing and the number of embryos transferred. RESULTS AND CONCLUSIONS: The pregnancy (positive hCG) and clinical pregnancy rates were 25.8 and 21.1%, respectively. A total of 107 (33.3%) of the 321 pregnancies identified by a positive hCG test miscarried either before (18.4%) or after (15%) the clinical recognition of gestational sac(s). The delivery rate for the frozen embryo transfers analysed was 17.2%. Our data revealed that the delivery rate after frozen embryo transfer was dependent on both the woman's age and the quality of embryos transferred, at the same time being unaffected by IVF/ICSI treatment. In addition, the increased woman's age at IVF/ICSI treatment was identified as the only parameter elevating the biochemical pregnancy rate, whereas the clinical abortion rate was found to be unrelated to the clinical or embryological parameters studied.     

Predictors of ongoing implantation in IVF in a good prognosis group of patients

BACKGROUND: The aim of this study was to investigate whether, in a large randomized trial, it is possible to identify specific maternal and/or embryo variables that could independently correlate with ongoing implantation in IVF/ICSI. METHODS: In a Scandinavian study, 661 women were randomized to elective single embryo transfer or double embryo transfer. Women aged <36 years undergoing their first or second IVF cycle and with at least two good quality embryos were eligible. Only one cycle per subject was included. In the present study, cycles with 0 or 100% ongoing implantation (n = 520) were analysed regarding maternal and embryo variables. RESULTS: In this selected study group, the ongoing implantation rate was 195/734 (26.6%). In the univariate analysis, first IVF cycle, conventional IVF as fertilization method and 4-cell embryos showed a statistically higher ongoing implantation rate than did second IVF cycle, ICSI and non-4-cell embryos. In the multivariate analysis the same variables correlated independently to ongoing implantation. In addition, ovarian sensitivity correlated independently to ongoing implantation. CONCLUSION: This information should be used when selecting the number of embryos for transfer with the overall aim to reduce the rate of multiple births while maintaining a satisfactory birth rate.     

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer

Controversy exists as to whether the serum concentration ofprogesterone on the day of human chorionic gonadotrophin (HCG)administration following ovarian stimulation for in-vitro fertilization(IVF) and embryo transfer can be used to predict the likelihoodof success. This retrospective study was undertaken to answerthis question by analysing a large population of IVF and embryotransfer cycles (n = 756). In addition to the concentrationof progesterone on the day of HCG administration, all variablesknown to impact on IVF and embryo transfer success (such aspatient age), indication for IVF and embryo transfer, numberof oocytes retrieved and the number of embryos generated andtransferred were examined. There was a significant increasein the number of oocytes retrieved with increasing progesteroneconcentration at the time of HCG administration. However, therewas no correlation of progesterone concentration at HCG administrationwith pregnancy and implantation rates. It is concluded thatprevious reports associating a slight elevation of progesteronein gonadotrophin- releasing hormone agonist ovarian stimulationcycles for IVF and embryo transfer may be misleading becauseof a small sample size or the presence of confounding variablesthat affect IVF and embryo transfer success.     

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.     

Serum HCG 12 days after embryo transfer in predicting pregnancy outcome

BACKGROUND: Assisted reproduction treatment (ART) entails a risk of ectopic pregnancy and early pregnancy loss. Serum HCG has been found to be predictive of pregnancy outcome. Our aim was to assess the clinical value of a single early HCG assay in ART pregnancies taking into account the aetiology and treatment of infertility. METHODS: During 1994-1999, we studied 774 embryo transfer cycles resulting in pregnancy defined as a serum HCG concentration of > or =5 IU/l on day 12 following embryo transfer. The treatment included IVF in 518, ICSI in 119, and frozen embryo transfer in 137 cycles. Serum HCG concentrations were measured by fluoroimmunometric assay. Pregnancies were classified as viable (live fetus at > or =22 weeks gestation) or non-viable (biochemical pregnancy, miscarriage, ectopic pregnancy and molar pregnancy). Data on the outcomes were retrospectively retrieved from the records. RESULTS: The median HCG concentration was 126 IU/l in viable pregnancies and 31 IU/l in non-viable pregnancies (P < 0.0001). The median HCG concentration was 115 IU/l in singleton pregnancies and 201 IU/l in multiple pregnancies (P < 0.0001). Male factor infertility was associated with viable pregnancies (P = 0.004) and tubal factor with non-viable pregnancies (P = 0.003); the lowest HCG level (88 IU/l) was observed in subjects with both male factor infertility and ICSI treatment (P = 0.001). An HCG value of 76 IU/l emerged as the most suitable cut-off point to predict viable pregnancy. Probabilities of each type of outcome related to the HCG level are given. CONCLUSIONS: A single HCG reading on day 12 after embryo transfer helps to plan the subsequent follow-up. Male factor infertility and ICSI are associated with relatively low HCG values in viable pregnancies.     

One year's experience with elective transfer of two good quality embryos in the human in-vitro fertilization and intracytoplasmic sperm injection programmes

High incidences of multiple pregnancies, after transferringa maximum of three embryos, were observed after in-vitro fertilization(IVF) treatment. In a randomized study, it was demonstratedthat, after taking into account embryo quality and other positivelyinterfering parameters, an elective transfer of two good qualityembryos does not significantly influence the pregnancy rate.The intracytoplasmic sperm injection (ICSI) technique was successfullydeveloped in the meantime and high incidences of multiple pregnancieswere also obtained after ICSI. The question arose whether afterICSI there was also room for elective double embryo transferin a well-defined patient group. This report covers 1 year of IVF and ICSI treatment and theresults are presented in relation to the number of embryos transferred.The embryo development is similar for zygotes obtained afterIVF and ICSI; for both techniques 63% of the zygotes developto type A-B embryos and 13% to type C embryos. There is alsono difference in the pregnancy rate after ICSI or IVF. Globally,after IVF, 307 out of the 766 double and triple transfers (40.1%)and 317 out of 774 double and triple transfers (40.9%) afterICSI resulted in a positive HCG. After IVF, 73.9% (227) andafter ICSI 76.3% (242) of the pregnancies were evolutive. Neitherwas there any difference between the two techniques as regardsthe implantation rate per transferred embryo. After IVF, 22.8%of the transferred embryos implanted compared with 21.8% afterICSI. When the elective double embryo transfers were compared,no difference was found between IVF and ICSI. After IVF, 102of the 211 elective double transfers (48.1%) resulted in a pregnancyversus 93 out of 225 (41.3%) after ICSI [not significant (NS)].A high implantation rate per transferred embryo (IVF: 33.2%;ICSI: 26.9%, NS) was obtained in this elective double transfercategory, as was also reported in the randomized study. Thesedata confirm the results obtained in our randomized study andthe effectiveness of the elective double embryo transfer forIVF as well as for ICSI.     

A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles

BACKGROUND: We analysed the difference in maternal, neonatal and total costs after single (SET) versus double day 3 embryo transfer (DET). METHODS: We performed a two-centre prospective study of women in their first IVF/ICSI cycle choosing between SET or DET. Infertility treatment data were gathered from a database; maternal and neonatal outcome data from a case report form (CRF); health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills. SET was performed in 206/367 (56.1%) and DET in 161/367 (43.9%) women. RESULTS: In all, 367 transfers yielded 186 positive pregnancy tests, 148 ongoing pregnancies and 136 live deliveries (50.7, 40.3 and 37.1% per embryo transfer) of which 15 (11.0%) were twins. Live birth rate was 37.4% for SET, 36.6% for DET. Intention-to-treat analysis showed differences for: duration of pregnancy (SET: 39.0 +/- 1.4 versus DET: 38.3 +/- 2.2 weeks; P = 0.055), percentage prematurity (8.5 versus 23.8%; P = 0.033), percentage of neonates hospitalized (5.7 versus 17.9%; P = 0.121) and duration of neonatal hospitalization (6.3 +/- 2.2 versus 10.3 +/- 10.1 days; P = 0.01). Total cost after DET was higher (SET: 4700 +/- 3239 versus DET: 8613 +/- 10 105; P = 0.105), due to significantly higher neonatal costs (451 +/- 957 versus 3453 +/- 8154; P < 0.001) and not to differences in maternal costs (4250 +/- 2882 versus 5160 +/- 4106; P = 0.152). CONCLUSIONS: This prospective health economic study shows that transfer of a single top quality embryo is equally effective as, but substantially cheaper than, double embryo transfer in women <38 years of age in their first IVF/ICSI cycle.     

Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.     

Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles

BACKGROUND: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET). MATERIALS AND METHODS: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate. RESULTS: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ. CONCLUSION: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.     

Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. ESHRE Campus Course Report

Twin pregnancies constitute the most serious complication for both mother and children after IVF/ICSI treatment, but transfer of at least two 'best looking' embryos remains the standard policy. This is due to our inability and reluctance to identify both the 'twin prone' patient and the top quality embryo. Some centres now electively transfer a single embryo (eSET) when particular embryo quality and patient criteria are met. Results from several centres were presented during an ESHRE Campus Course, held on May 6(th) 2000. Sound clinical trials are needed to clarify several points of discussion. What is the clinical profile of patients in whom eSET should be considered? Will the overall (ongoing) pregnancy rate of the IVF/ICSI programme decrease if eSET is performed in these patients? What is the twinning rate when eSET is a routine policy? Will the financial gain by avoiding perinatal hospitalization costs of prevented twins be balanced by the likely need to perform a number of extra IVF/ICSI cycles? What will be gained by freezing the extra number of high quality embryos? Should eSET be performed at the 2 pronuclear stage, the early cleaving embryo or the blastocyst stage? Common sense dictates that eSET as a concept should be applied from now onwards.     

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.     

Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study

BACKGROUND: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. METHODS: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. RESULTS: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. CONCLUSIONS: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.