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.     

Cervical dilatation has a positive impact on the outcome of IVF in randomly assigned cases having two previous difficult embryo transfers

BACKGROUND: The difficulty of embryo transfer has been reported to affect success rates in some centres, but not in others. Cervical dilatation has been proposed as a means to overcome difficult embryo transfer, but consistent criteria for patient selection are lacking. In a prospective randomized study, we examined the influence of cervical dilatation 1-3 months before embryo transfer on the outcome of IVF in cases having difficult embryo transfer in two previously failed IVF cycles. METHODS: Two alternative methods of embryo transfer preparation were evaluated in 283 randomly assigned women having difficult embryo transfers in two previously failed IVF attempts. Randomization was made using a computer-generated random number table. Cervical dilatation before starting any IVF treatment was used in 145 cases, and no dilatation was performed in 138 cases. RESULTS: The cervical dilatation group yielded a significantly higher pregnancy rate than the non-dilated group (40% versus 24%; P < 0.01). Likewise, the implantation rate (24.1% versus 14.9%; P < 0.01) and the live birth rate (34.48% versus 19.56%; P < 0.01) were significantly higher in the dilatation group than in the non-dilated group. CONCLUSIONS: In patients with prior difficult embryo transfer, cervical dilatation 1-3 months before embryo transfer lead to an improved pregnancy rate.     

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 prospective randomized study: day 2 versus day 5 embryo transfer

BACKGROUND: This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers. METHODS: Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred. RESULTS: The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%). CONCLUSION: This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.     

Comparison between day-2 embryos obtained either from ICSI or resulting from short insemination IVF: influence of maternal age

Short incubation time prevents deleterious effects of cumulus cell degeneration and excess spermatozoa in IVF embryos. We performed a short incubation (3 h) protocol in 328 IVF cycles, in order to compare the developmental potential of regular IVF embryos with those originating from 316 cycles entered our intracytoplasmic sperm injection (ICSI) programme over the same period. Embryo transfers were performed in all patients on day 2. The mean number of embryos transferred was 1.92 for the ICSI group and 1.73 for the IVF group (P < 0.007). This was related only to the wishes of patients. However, the policy of the centre is to transfer a low number of embryos in young patients in order to avoid multiple pregnancies. All spare embryos were permitted to grow to the blastocyst stage for freezing. Shortening incubation time did not decrease fertilization rates. In our overall population, no difference was observed in the implantation rates per embryo for IVF (19%) or for ICSI (20%). An age-related decrease in embryo production was observed for both groups of patients (P < 0.01 for ICSI and P < 0.001 for IVF). The age-related decrease in embryo implantation was only significant for the IVF group (P < 0.03 for patients <30 and >35 years of age). A significant overall decrease in blastocyst formation was observed for spare embryos after ICSI versus IVF (34.2 versus 43.8%; P < 0. 05). The significance of this observation is discussed.     

Andrology: Factors influencing the outcome of in-vitro fertilization with epididymal spermatozoa in irreversible obstructive azoospermia

Microsurgical epididymal sperm aspiration (MESA) and in-vitrofertilization (IVF) were found to offer limited opportunityfor fatherhood to 45 men with obstructive azoospermia, due principallyto poor embryo implantation. Adequate sperm preparations wereobtained in 46/50 treatment cycles (92%), with the best motilityfound in the caput epididymis in 89% of cases. The mean fertilizationrate was 11.2% and fertilization occurred in 23 cycles (50%),with embryo transfer arising from 12/26 men with was aplasia(CAV), 4/9 with genital tract obstruction (EV) and 7/11 withirreversible vasectomy (VV). The overall implantation rate waslow, 8.7% per embryo transfer (11.7% per 2-3 embryo transfers)and was not improved by Fallopian transfer. There were two pregnancies(4% per cycle), both in the EV group where embryo formationand implatation (2/4, 50% per cycle) were optimum even thoughsperm preparations were paradoxically inferior to the CAV andVV groups. The spermatozoa retrieved in the two successful EVcycles were appreciably blood contaminated. Analysis of the21 failed embryo transfers showed delayed fertilization in 10cycles, cystic fibrosis (CF) mutation or familial disease in7/12 CAV men and the VV men were older (P<0.001). A pregnancywhich miscarried arose from a case of Young's syndrome, a carrierof CF mutation DF508. Male factors could thus be implicatedin the high embryo wastage of MESA cycles and might also beinfluencing implantation in other IVF procedures. Where feasible,male reconstructive surgery is preferable unless fertilizationcan be improved, possibly by speedier retrieval techniques orby permitting sperm capacitation in vitro, but probably moreeffectively by micro-assisted insemination.     

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.     

The effect of intercourse on pregnancy rates during assisted human reproduction

Intercourse during an IVF cycle has the potential to improve pregnancy rates since exposure to semen is reported to promote embryo development and implantation in animals. Conversely, coitus-induced uterine contractions or introduction of infection may have a detrimental effect. A multicentre prospective randomized control trial was conducted to determine if intercourse during the peri-transfer period of an IVF cycle has any influence on pregnancy success. Participants undergoing thawed embryo transfer (Australian centre) or fresh embryo transfers (Spanish centres) were randomized either to abstain or to engage in vaginal intercourse around the time of embryo transfer. The transfer of 1343 embryos during 478 cycles of IVF resulted in 107 pregnancies (22.4%), with 125 viable embryos remaining by 6-8 weeks gestation. There was no significant difference between the intercourse and abstain groups in relation to the pregnancy rate (23.6 and 21.2% respectively), but the proportion of transferred embryos that were viable at 6-8 weeks was significantly higher in women exposed to semen compared to those who abstained (11.01 versus 7.69 viable embryos per 100 transferred embryos, P = 0.036, odds ratio 1.48, 95% confidence interval 1.01-2.19). Hence exposure to semen around the time of embryo transfer increases the likelihood of successful early embryo implantation and development.     

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.     

Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: a pilot study

BACKGROUND: The use of the natural cycle for IVF offers the advantage of a patient-friendly and low-risk protocol. Its effectiveness is limited, but may be improved by using a GnRH antagonist to prevent untimely LH surges. METHODS: In this pilot study, minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and simultaneous substitution with recombinant FSH was applied for a maximum of three cycles per patient. Main outcome measures were pregnancy rates per started cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 50 patients completed 119 cycles (2.4 per patient). Fifty-two embryo transfers resulted in 17 ongoing pregnancies [14.3% per started cycle; 32.7% per embryo transfer; 95% confidence interval (CI) 7.9-20.7% and 19.7-45.7%, respectively]. One dizygotic twin pregnancy occurred after transfer of two embryos, the other pregnancies were singletons. The cumulative ongoing pregnancy rate after three cycles was 34% (95% CI 20.6-47.4%). Live birth rate was 32% per patient (95% CI 18.8-45.2%). CONCLUSIONS: Pregnancy rates after IVF with minimal, late follicular phase stimulation are encouraging. Considering the low-risk and patient-friendly nature of this protocol, it may be a feasible alternative to IVF with ovarian hyperstimulation.     

Ratio of oestradiol concentration on the day of human chorionic gonadotrophin administration to mid-luteal oestradiol concentration is predictive of in-vitro fertilization outcome.

The role of luteal oestradiol for successful implantation in humans seems to be permissive rather than obligatory. Few studies have attempted to clarify the role of early luteal oestradiol in in-vitro fertilization (IVF) outcome, whether peri-implantation oestradiol is predictive of successful IVF outcome. We retrospectively analysed 106 women undergoing 106 IVF/embryo transfer cycles. Only the first treatment cycle per patient was analysed. Peak oestradiol denoted the concentration on the day of human chorionic gonadotrophin (HCG) administration. Mid-luteal oestradiol was obtained 3 days after embryo transfer (8 days after HCG administration). A total of 44 pregnancies were noted (41.51%). There were no differences in age, cycle day 3 follicle stimulating hormone (FSH), peak oestradiol, number of retrieved oocytes, number of embryo transfers, and mid-luteal oestradiol between pregnant and non-pregnant women. However, the ratio of day of HCG oestradiol to mid-luteal oestradiol was highly predictive of successful outcome: the ongoing pregnancy rate and implantation rate (sacs with fetal heart beat/embryo transfer) were 15.8 and 5.7% respectively if the above ratio exceeded 5.0 (n = 19), compared to 42.1 and 16.3%, and 53.3 and 26. 5% if the ratio was between 0.4 and 2.5 (n = 57), and between 2.5 and 5.0 (n = 30) respectively. Our study suggests that the magnitude of decline in oestradiol concentrations after oocyte retrieval may be important in predicting IVF success. We postulate that endometrial integrity may become compromised when a dramatic drop in oestradiol occurs by the mid-luteal period. Whether these women benefit from oestradiol supplementation after oocyte retrieval remains to be investigated.     

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.     

Assisted reproductive technology in Europe, 1999. Results generated from European registers by ESHRE

European results of assisted reproductive techniques from treatments initiated during 1999, are presented in this third report. Data were collected mainly from pre-existing national registers. From 22 countries 538 clinics reported 258 460 cycles: IVF 125 370, ICSI 95 221, frozen embryo replacement (FER) 34 002 and oocyte donations (OD) 3867. In eight countries, where all clinics reported to the register, a total of 99 629 cycles was performed in a population of nearly 106 million, corresponding to 943 cycles per million inhabitants and 3.9 cycles per 1000 women aged 15-49 years. After IVF and ICSI the distribution of transfer of 1, 2, 3 and >or=4 or more embryos was 11.9, 39.2, 39.6 and 9.3% respectively. Huge differences existed between countries. For IVF the clinical pregnancy rate per aspiration and per transfer was 24.2 and 27.7% respectively. For ICSI the corresponding rates were 26.1 and 27.9%. These figures represent relative increases by 2.2 to 5.2% compared with 1998. The distribution of singleton, twin, triplet and quadruplet deliveries for IVF and ICSI combined was 73.7, 24.0, 2.2 and 0.1%. This gives a total multiple delivery rate of 26.3%. Triplet deliveries after IVF and ICSI ranged from 0.3-7.0% between countries. Compared with 1998, the number of reported cycles increased by 11% and the clinical pregnancy rate per transfer increased from 27.0 to 27.7% after IVF and from 26.8 to 27.9% after ICSI. Multiple deliveries after IVF and ICSI remained unchanged at 26.3% in 1999.     

Is there any benefit from the culture of a single oocyte to a blastocyst-stage embryo in unstimulated cycles?

BACKGROUND: The aim of the study was to test the influence of 2- and 5-day cultivation of a single oocyte on the pregnancy rate in a non-stimulated cycle. METHODS: A retrospective chart review of 391 consecutive patients undergoing IVF and intracytoplasmic sperm injection in unstimulated cycles was performed. The embryos were kept in MediCult universal IVF medium for day 2 transfers and in BlastAssist System for day 5 transfers. RESULTS: The oocyte recovery rate in the group for 2-day cultivation and in the group for 5-day cultivation was similar, being 79.4 (162/204) and 83.6% (154/187) respectively. The same is true of the fertilization rate (73.8 versus 77.7%). The blastulation rate was 52.8%. The embryo transfer rate per cycle was higher when day 2 embryos were transferred: 64.8% (105/162) compared with 35.7% (55/154) if blastocyst-stage embryos were transferred. The pregnancy rate per transferred embryo was higher when a blastocyst was transferred (40.0%) instead of a day 2 embryo (23.8%). CONCLUSION: The expected pregnancy rate calculated per embryo available on day 2 of cultivation was similar in both groups (23.8 versus 22.2%) and it was not affected by oocyte culture to the blastocyst stage.     

Hydrosalpinx affects the implantation of previously cryopreserved embryos

The presence of hydrosalpinx has been reported to negativelyaffect the pregnancy and implantation rate after in-vitro fertilization(IVF) with embryo transfer. Hydro-salpinges are able to enlargeduring ovarian stimulation with a possible increased passageof tubal fluid into the endometrial cavity. We report the effectof hydrosalpinges during the transfer of previously cryopreserved/thawedembryos during a natural cycle. In all, 14 transfers in 10 patientswith a sonographically-documented hydrosalpinx during the studiedcycle (group I) were compared to 98 cycles in 74 patients withtubal disease but no such sonographic finding (group II). Bothpregnancy and implantation rates were significantly lower ingroup I (7.14 versus 24.49% and 5.0 versus 10.8% respectively).The presence of hydrosalpinx negatively affects pregnancy andimplantation rates during natural cycles.     

Assisted reproductive technology in Europe, 2000. Results generated from European registers by ESHRE

European results of assisted reproductive techniques from treatments initiated during 2000 are presented in this fourth annual report. Data were collected mainly from pre-existing national registers. From 22 countries, 569 clinics reported 279 267 cycles: IVF 126 961, ICSI 99 976, frozen embryo replacement (FER) 45 800 and oocyte donations (OD) 6530. In nine countries where all clinics reported to the register, a total of 142 174 cycles were performed in a population of 166 million, corresponding to 856 cycles per million inhabitants. After IVF and ICSI, the distribution of transfer of one, two, three and >or=4 embryos was 12.1, 46.7, 33.3 and 6.8%, respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per aspiration and per transfer was 24.7 and 28.4%, respectively. For ICSI, the corresponding rates were 26,6% and 28,7%. These figures represent increases of 0.7 and 0.8% compared with 1999. The distribution of singleton, twin, triplet and quadruplet deliveries for IVF and ICSI combined was 73.6, 24.4, 2.0 and 0.04%. This gives a total multiple delivery rate of 26.4%. The range of triplet deliveries after IVF and ICSI ranged from 0.3 to 7.0% between countries. Compared with 1999, the number of reported cycles was increased by 8% and the clinical pregnancy rate per transfer was increased by 0.7% after IVF and by 0.8% after ICSI. The total multiple delivery rates after IVF and ICSI remain unchanged during the last 4 years.     

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.     

A randomized study comparing IVF in the unstimulated cycle with IVF following clomiphene citrate

The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only. A total of 132 couples with no previous IVF attempts, selected by female age <35 years, indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were randomized to the two protocols. Randomization yielded two comparable groups. The clomiphene group (68 couples) performed significantly better than the unstimulated group (64 couples) in terms of number of cycles with oocyte harvest (90/111 or 81% versus 65/114 or 57%; chi(2) = 9.21, P < 0.002), embryo transfers per started cycle (59/111 or 53% versus 29/114 or 25%; chi(2) = 18.14, P < 0.0001), live intrauterine pregnancy rate per started cycle (20/111 or 18% versus 4/114 or 4%; chi(2) = 12.42, P < 0.0001), live intrauterine pregnancy rate per embryo transfer (20/59 or 34% versus 4/29 or 14%; chi(2) = 3.96, P = 0.047), but not in terms of implantation rate (22/85 or 26% versus 4/29 or 14%; chi(2) = 1.65). Only two twin pregnancies occurred. Modest side-effects were recorded following clomiphene. Accordingly, a simple clomiphene citrate protocol, but not IVF in unstimulated cycles, seems compatible with the concept of 'friendly IVF', yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients. The results do not substantiate any important negative anti-oestrogenic effects of clomiphene.     

High fertilization and implantation rates after intracytoplasmic sperm injection

Previously reported better fertilization rate after intra-cytoplasmicsingle sperm injection (ICSI) than after subzonal inseminationof several spermatozoa was confirmed in a controlled comparisonof the two procedures in 11 patients. Intracytoplasmic sperminjection was carried out in 150 consecutive treatment cyclesof 150 infertile couples, who had failed to have fertilizedoocytes after standard in-vitro fertilization (IVF) proceduresor who were not accepted for IVF because not enough motile spermatozoawere present in the ejaculate. A single spermatozoon was injectedinto the ooplasm of 1409 metaphase II oocytes. Only 117 oocytes(8.3%) were damaged by the procedure and 830 oocytes (64.2%of the successfully injected oocytes) had two distinct pronucleithe morning after the injection procedure. The fertilizationrate was not influenced by semen characteristics. After 24 hof further in-vitro culture, 71.2% of these oocytes developedinto embryos, which were transferred or cryopreserved. Only15 patients did not have embryos replaced. Three-quarters ofthe transfers were triple-embryo transfers. High pregnancy rateswere noticed since 67 pregnancies were achieved, of which 53were clinical, i.e. a total and clinical pregnancy rate of 44.7%and 35.3% per started cycle and 49.6% and 39.2% per embryo transfer.A total of 237 supernumerary embryos were cryopreserved in 71treatment cycles.     

Multiple-birth risk associated with IVF and extended embryo culture: USA, 2001

BACKGROUND: Multiple births are associated with serious adverse infant and maternal outcomes. The objective of this study was to assess the multiple-birth risk (MBR) associated with IVF and determine whether the risk is impacted by stage of embryo development at transfer. METHODS: A population-based sample of 50 819 IVF transfers utilizing day 3 or day 5 embryos performed in the USA in 2001 on women aged 20-40 years was used to assess MBR and live-birth rate (LBR), stratified by patient age, supernumerary embryo availability, and number of embryos transferred. RESULTS: Although significantly more day 5 than day 3 transfers used < or =2 embryos (69.2 versus 27.7%), the former were not associated with decreased MBR. MBR was high when >1 embryo was transferred, irrespective of embryo development stage. LBR were generally maximized with 2 embryos transferred, and for some (day 5 transfers, patients aged 35-37 years) with one embryo. Electing to transfer a single day 5 embryo appeared efficacious for some patients: women aged 20-37 years with supernumerary embryos cryopreserved had LBR of 31.6-39.5%. CONCLUSIONS: MBR is high when > or =2 embryos are transferred. Single embryo transfer is the only way to prevent many multiple births and associated adverse health outcomes.