Complete Fertilization Failure Research Articles

Split ICSI/Insemination in Mild Male Factor Infertility: a Randomized Controlled Trial

Introduction: Intracytoplasmic sperm injection (ICSI) is a widely used adjunct to in vitro fertilization (IVF) for male-factor infertility when fertilization failure is suspected. In patients with borderline semen, the decision to choose either IVF or ICSI is critical because the chance of total fertilization failure after a conventional IVF or of performing an unnecessary ICSI procedure is hard to predict. Objective: The purpose of this study was to assess the value of the allocation of some eggs to ICSI and others to conventional insemination (Split ICSI/insemination) in IVF cycles in which semen parameters are subfertile. Design: It is prospective study. Materials and methods: Between August 2007 and April 2010, 190 patients had half of their eggs inseminated with ICSI and the other half inseminated with conventional IVF. Results: In this study, 76.3% of patients were fertilized by both IVF and ICSI, 21.6% of patients were fertilized only by ICSI while 2.1% of patients were not fertilized either by IVF or ICSI. Fertilization rate was significantly higher in oocytes injected by ICSI (63.7%) compared to oocyte inseminated by IVF (44.3%). In patients fertilized by both IVF and ICSI, although ICSI fertilization rate was higher (65.9%) than IVF fertilization rate (57.3%), yet there is no significant differences were observed. High grade embryos were significantly higher in oocytes injected by ICSI (75.9%) compared to oocyte inseminated by IVF (56.4%). Also, significantly more type 1 and 2 embryos developed after ICSI compared with IVF (77.3% vs. 56.4%) in the group of patients with fertilization after both IVF and ICSI. Conclusion: According to our findings, implementation of ICSI in couples with mild male factor infertility could improve fertilization rates and decrease the risk of complete fertilization failure. Additionally, split ICSI procedure provides valuable clinical information about fertilization potential for the couple and unnecessary use of ICSI procedure can be avoided in future cycles for patients who have achieved good fertilization in both IVF and ICSI.

Split ICSI/Insemination in Mild Male Factor Infertility: a Randomized Controlled Trial

Introduction: Intracytoplasmic sperm injection (ICSI) is a widely used adjunct to in vitro fertilization (IVF) for male-factor infertility when fertilization failure is suspected. In patients with borderline semen, the decision to choose either IVF or ICSI is critical because the chance of total fertilization failure after a conventional IVF or of performing an unnecessary ICSI procedure is hard to predict. Objective: The purpose of this study was to assess the value of the allocation of some eggs to ICSI and others to conventional insemination (Split ICSI/insemination) in IVF cycles in which semen parameters are subfertile. Design: It is prospective study. Materials and methods: Between August 2007 and April 2010, 190 patients had half of their eggs inseminated with ICSI and the other half inseminated with conventional IVF. Results: In this study, 76.3% of patients were fertilized by both IVF and ICSI, 21.6% of patients were fertilized only by ICSI while 2.1% of patients were not fertilized either by IVF or ICSI. Fertilization rate was significantly higher in oocytes injected by ICSI (63.7%) compared to oocyte inseminated by IVF (44.3%). In patients fertilized by both IVF and ICSI, although ICSI fertilization rate was higher (65.9%) than IVF fertilization rate (57.3%), yet there is no significant differences were observed. High grade embryos were significantly higher in oocytes injected by ICSI (75.9%) compared to oocyte inseminated by IVF (56.4%). Also, significantly more type 1 and 2 embryos developed after ICSI compared with IVF (77.3% vs. 56.4%) in the group of patients with fertilization after both IVF and ICSI. Conclusion: According to our findings, implementation of ICSI in couples with mild male factor infertility could improve fertilization rates and decrease the risk of complete fertilization failure. Additionally, split ICSI procedure provides valuable clinical information about fertilization potential for the couple and unnecessary use of ICSI procedure can be avoided in future cycles for patients who have achieved good fertilization in both IVF and ICSI.

FIV conventionnelle versus ICSI sur une même cohorte ovocytaire : analyse de l’expérience française pour les BLEFCO

Assisted Reproductive Techniques (ART) separating oocytes in sibling oocytes treated either by conventional IVF or ICSI is called mid-IVF/ICSI. We sum up here 487 attempts of this kind from six French ART centers. The mid-IVF/ICSI technique was performed in 5.6% of cases. The fertilization rate by micro-injected oocytes was significantly higher ( P < 0.01) than oocytes inseminated conventionally, 72.6% versus 53.4%. A failure of fertilization was observed only in mid-IVF in 21.6% of cases, which prevented a complete fertilization failure when we decided to propose to the couples concerned the mid-IVF/ICSI technique. Conversely, in 75.2% of cases, fertilization was found for the two batches of oocytes. The overall pregnancy rate has improved since the use of the mid-IVF/ICSI technique (33.1% versus 28.9%, P = 0.013) and the fertilization failures decreased (10.4% versus 14.3%, P = 0. 019). The pregnancy rate in only mid-IVF/ICSI cases is very high at 39.8% but for a selected population. The indications for mid-IVF/ICSI remain to be clarified especially with regard to male and idiopathic indications.

Oocyte activation, phospholipase C zeta and human infertility

Mammalian oocytes are activated by intracellular calcium (Ca(2+)) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C zeta, PLCζ, which is introduced into the oocyte following membrane fusion, as the responsible factor. This review summarizes the current understanding of human oocyte activation failure and describes recent discoveries linking certain cases of male infertility with defects in PLCζ expression and activity. How these latest findings may influence future diagnosis and treatment options are also discussed. Systematic literature searches were performed using PubMed, ISI-Web of Knowledge and The Cochrane Library. We also scrutinized material from the United Nations and World Health Organization databases (UNWHO) and the Human Fertilization and Embryology Authority (HFEA). Although ICSI results in average fertilization rates of 70%, complete or virtually complete fertilization failure still occurs in 1-5% of ICSI cycles. While oocyte activation failure can, in some cases, be overcome by artificial oocyte activators such as calcium ionophores, a more physiological oocyte activation agent might release Ca(2+) within the oocyte in a more efficient and controlled manner. As PLCζ is now widely considered to be the physiological agent responsible for activating mammalian oocytes, it represents both a novel diagnostic biomarker of oocyte activation capability and a possible mode of treatment for certain types of male infertility.

Progesterone receptor requires a co-chaperone for signalling in uterine biology and implantation.

Embryo implantation is absolutely dependent on the preparation of the uterus to the receptive stage and attainment by the blastocyst of implantation competency. Co-ordinated effects of progesterone and oestrogen are essential for these processes and determine the window of implantation. In rodents, a generalized stromal edema occurs before blastocyst attachment followed by uterine luminal closure. This leads to apposition of the blastocyst trophectoderm against the luminal epithelium and ultimately attachment. Progesterone is essential for luminal closure, which must occur for successful implantation. More importantly, progesterone is critical for almost every stage of pregnancy, including ovulation, fertilization, implantation, decidualization and pregnancy maintenance. Progesterone exerts its effects on target tissues primarily via nuclear progesterone receptor (PR) whose optimal activity is potentiated by an immunophilin co-chaperone, FK-506 binding protein 4 (FKBP52). While mice lacking PR are infertile due to complete failure of ovulation, fertilization, and implantation, female mice with targeted deletion of the Fkbp52 gene are infertile specifically because of implantation failure resulting from compromised uterine receptivity. This review highlights the evolution of knowledge about progesterone signalling during early pregnancy. Future studies are likely to provide a better understanding of FKBP52-PR signalling in promoting uterine receptivity for implantation and may reveal new targets for improving infertility.

RETRACTED: Failed fertilization after clinical intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI) has resulted in pregnancy and birth for many couples, including those with severe male factor infertility. However, even after ICSI, complete failure of fertilization occurs in 1-3% of cycles. Most cases occur due to low number of mature oocytes, failure of oocyte activation or non-availability of appropriate spermatozoa for injection. Given the significant emotional and financial involvement in assisted reproductive cycles, failure of fertilization in all mature oocytes is a distressful event. It is not predictable. Since follow-up ICSI cycles result in fertilization in 85% of cases, repeated ICSI attempts are suggested. Physicians should counsel patients experiencing repeated failure of fertilization after ICSI cycles about available options including donated oocytes/embryos, donor sperm insemination, adoption or remaining childless if these choices are not acceptable due to religious or ethical reasons. This review discusses the causes and remedies for failed fertilization after clinical ICSI.

Infertilité masculine chez les patients normospermiques : analyse protéomique des spermes normaux non fécondants en fécondation in vitro classique

Objective Despite normal sperm parameters, 5% of in vitro fertilization (IVF) attempts result in an unpredictable failure of fertilization. In 56% of the cases, there is no obvious oocyte anomaly, but lack of sperm binding to the zona pellucida. This study aims to contribute to clarify the male molecular causes of failures in IVF, which are undetected by classical sperm analysis. Patients and methods The spermatic proteomic profiles of patients, with a complete failure of fertilization and no spermatozoa bound to the zona pellucida, is compared to controls (patients with normal fertilization and cleavage rates after a classical IVF for tubal indication). All samples are analysed by 2 Dimensional Electrophoresis-Differential In Gel Electrophoresis (2DE-DIGE) after being divided into three fractions according to their isoelectric point (acid, intermediate and basic). Results Fourteen proteins differentially expressed between all the cases and all the controls were highlighted. Twelve of these proteins were identified by mass spectrometry (six from the acid fraction and six from the basic fraction). Two of these proteins may have an interest in gametic interaction: the laminin receptor LR67 and the L-xylulose reductase. Discussion and conclusion More investigation is needed to understand the involvement of the identified proteins in the IVF fertilization failure of the infertile patients in this study.

Comparison of in vitro fertilization versus intracytoplasmic sperm injection in extremely low oocyte retrieval cycles

To compare the results of IVF and intracytoplasmic sperm injection (ICSI) in extremely low oocyte retrieval cycles. Case-control study. An IVF laboratory in a university hospital in Taiwan. Between January 2003 and December 2007, infertile couples with one, two, or three oocytes per retrieval were divided into two groups: 56 IVF cycles based on 28 demographic characteristics from the ICSI group. None. Fertilization rate, cycle cancellation rate, clinical pregnancy rate, and implantation rate per transfer. The normal fertilization rate was significantly higher after ICSI than after standard IVF (86.4% vs. 69.3%). The cycle cancellation and complete fertilization failure rates were comparable between the two groups. The clinical pregnancy rate per transfer (38.5% vs. 21.6%), implantation rate (23.5% vs. 11.1%), and live birth rate per transfer (30.8% vs. 13.7%) had a favorable trend, but no statistically significant differences, in the ICSI group compared with the IVF group. A higher normal fertilization rate can be achieved by ICSI in comparison with conventional IVF in extremely low oocyte retrieval cycles.

Analysis of complete fertilization failure following IVF treatment and comparison with subsequent ICSI outcomes

OBJECTIVE: Complete fertilization failure occurs infrequently in IVF cycles for non-male factors but is emotionally devastating for the couples involved and poses a management challenge. While ICSI is generally recommended to minimize recurrence, no studies have contrasted these failed IVF cycles with subsequent ICSI cycles in the same couples. The purpose of this study was to characterize these failed IVF cycles and to explore potential, underlying causes for complete fertilization failure.

Use and Outcomes of Intracytoplasmic Sperm Injection for Non-Male Factor Infertility

Although the use of intracytoplasmic sperm injection (ICSI) continues to increase in the United States, its effectiveness for patients without male factor infertility has never been convincingly demonstrated. In these patients, success rates are generally lower in those who use ICSI. This technique was evaluated in 486 patients without a diagnosis of male factor infertility who had 696 consecutive assisted reproductive technology (ART) cycles, 597 with IVF and 99 with ICSI. The 2 groups were similar except for higher rates of unexplained infertility and a previous ART cycle in the ICSI group and a higher rate of previous fertility in the IVF group. More oocytes were harvested in the IVF than in the ICSI group (9.0 versus 8.2), but the difference was not statistically significant. However, significantly more oocytes underwent IVF than ICSI (9.0 versus 7.4). The percentage of oocytes undergoing IVF also was significantly greater than the percentage undergoing ICSI. The difference in the mean numbers of oocytes fertilized, 6.6 for IVF and 5.1 for ICSI, was statistically significant. The fertilization rate was higher in the IVF group (74.1% versus 69.1%), but this difference was not significant. Rates of complete failure of fertilization were 3.2% for IVF and 4.0% for ICSI. In each group, 2.7 embryos on average were replaced. Approximately 95% of patients in each treatment group had at least 1 embryo replaced. There was no group difference in live birth rates. Logistic regression analysis revealed that a previous ART cycle was associated with ICSI, but choice of treatment could not be related to rates of fertilization, pregnancy, or live birth. This study failed to provide clear evidence of improved outcomes with ICSI compared with IVF in cases of nonmale factor infertility. The investigators find it difficult to justify this more expensive—and possibly less safe—procedure without clear evidence that it is beneficial.

The reproductive outcome of rescue ICSI cycles with a complete fertilization failure after in vitro fertilization insemination is conditioned by the number of oocytes reinseminated

The reproductive outcome of rescue ICSI cycles with a complete fertilization failure after in vitro fertilization insemination is conditioned by the number of oocytes reinseminated

Successful pregnancy after ICSI with strontium oocyte activation in low rates of fertilization

Fertilization failure (complete fertilization failure or low fertilization rates) after intracytoplasmic sperm injection (ICSI) can occur in rare cases. In the majority of these cases, the unfertilized oocytes are inactivated. Assisted oocyte activation was applied as a treatment option for a case of low fertilization rate as a clinical trial. A patient with a low fertilization rate (ranging from 0% to 33.3%; mean = 17.0%) after eight previous ICSI cycles at another hospital, was diagnosed with fertilization failure. The most likely cause of fertilization failure was failure of oocyte activation. Therefore, artificial oocyte activation by strontium treatment was combined with ICSI to achieve viable fertilized oocytes. Oocytes were stimulated with strontium (10 mM SrCl 2, 60 min) approximately 30 min after ICSl. Six injected oocytes were stimulated and all were then successfully fertilized. Two blastocysts were transferred into the uterus, resulting in a pregnancy and birth. A second pregnancy was achieved following implantation of two cryopreserved embryos (one blastocyst and one morula). In conclusion, strontium treatment was found to be an effective method for artificial oocyte activation in a case with a low fertilization rate after ICSI.

Progesterone receptor requires a co-chaperone for signalling in uterine biology and implantation

Embryo implantation is absolutely dependent on the preparation of the uterus to the receptive stage and attainment by the blastocyst of implantation competency. Co-ordinated effects of progesterone and oestrogen are essential for these processes and determine the window of implantation. In rodents, a generalized stromal edema occurs before blastocyst attachment followed by uterine luminal closure. This leads to apposition of the blastocyst trophectoderm against the luminal epithelium and ultimately attachment. Progesterone is essential for luminal closure, which must occur for successful implantation. More importantly, progesterone is critical for almost every stage of pregnancy, including ovulation, fertilization, implantation, decidualization and pregnancy maintenance. Progesterone exerts its effects on target tissues primarily via nuclear progesterone receptor (PR) whose optimal activity is potentiated by an immunophilin co-chaperone, FK-506 binding protein 4 (FKBP52). While mice lacking PR are infertile due to complete failure of ovulation, fertilization, and implantation, female mice with targeted deletion of the Fkbp52 gene are infertile specifically because of implantation failure resulting from compromised uterine receptivity. This review highlights the evolution of knowledge about progesterone signalling during early pregnancy. Future studies are likely to provide a better understanding of FKBP52-PR signalling in promoting uterine receptivity for implantation and may reveal new targets for improving infertility.

Investigating Unexpected Complete Fertilization Failure With ICSI

At times, an unexpected complete fertilization failure is observed and ICSI is performed on in vitro matured oocytes (D2 ICSI) the day of fertilization assessment. This fertilization failure is often observed in patients who have had a historical ICSI attempt with successful fertilization. This implies that the fertilization failure at the time of oocyte retrieval (D1) may be due to inadequate in vivo maturation. Here we analyze ovarian superovulation and their eventual effect on unexpected complete failure of fertilization in the study cycle. In a retrospective manner, we compared patients presenting a cycle with failed fertilization on day 1 (D1), and achieved fertilization on day 2. This cycle was also compared to previous, or reference, cycles with successful fertilization. Controls were age-matched and had fertilization on D1. From Jan 2001 to Jan 2004, patients with initial fertilization failure who fertilized the next day (D2 ICSI) were included. Only cycles with ejaculated spermatozoa (non-TESE) were included in the study. Patient age, BMI, proportion of urinary vs. recombinant medication, follicle size, maximum E2 level, oocyte number, in vivo/in vitro maturation time, ICSI operator, embryo quality, and pregnancy outcome were recorded. A total of 22 patients were identified during the three-year span. Twelve of these patients had a reference cycle with fertilization (D1) and were used for comparison. The age-matched controls included 22 patients with successful fertilization on D1. The semen parameters for the study group was an average of 50.8 x 106/ml concentration, 52.8% ± 23 motility, and 4.25 ± 3 morphology. There were no differences in age, type of protocol (agonist or antagonist), gonadotropin dose/type, ICSI operator, follicle size, E2 level, or days of stimulation between the three groups. There was, however, a shorter time lapse between HCG administration and time of ICSI in the study cycle vs. reference and age-matched control, 39h 6’ ± 1h 28’ (M ± SD) vs. 39h 53’ vs. 40h 17’ ± 58’, respectively (P < 0.01). In addition, BMI of the D2 ICSI group were also significantly higher than the age-matched patients (26.7 ± 6 vs. 22.0 ± 2; P < 0.01). There was an impaired pregnancy outcome in the study cycles in comparison to the other two groups. Tabled 1 This current study is the first to explore factors leading to, and resulting from, an unexpected fertilization failure with ICSI. Incubation of in vitro matured oocytes restored fertilization but resulted in extremely poor pregnancy outcome. This is an unsettling finding in a population with proven normal fertilization in historical IVF cycles. A shorter time interval between HCG administration and oocyte injection confirmed that inadequate in vivo maturation was responsible for the oocyte activation failure. Moreover, the presence of a higher BMI identified in the study group may represent an additional challenge in tailoring ovarian superovulation in this category of patients.

IVF versus ICSI in sibling oocytes from patients with polycystic ovarian syndrome: a randomized controlled trial

This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with polycystic ovarian syndrome (PCOS) and normozoospermic semen during IVF cycles. Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Fertilization rate (two pronuclei/COC), day 2 embryonic morphology and rate of development were assessed. A total of 1089 cumulus-oocyte complexes (COC) were collected in 60 cycles (mean+/-SD, 18.2 +/- 7.2). Totals of 541 and 548 COC were inseminated by IVF and ICSI respectively, with a significantly higher fertilization rate in the ICSI group (ICSI versus IVF, 72.3 +/- 15.5 versus 44.8 +/- 25.1%). No fertilization failure occurred in the group of oocytes inseminated by ICSI, whereas the COC in nine patients (15%) inseminated by IVF had complete fertilization failure. The day 2 embryonic morphology and rate of development were not different regardless of the insemination method. Our results suggested that another randomized controlled study, randomizing patients instead of sibling oocytes, should be undertaken to compare the pregnancy rate per started cycle and to see whether ICSI should be performed on all, or at least on a portion of, oocytes for patients with PCOS undergoing IVF cycles.

Prediction of outcomes of assisted reproduction treatment using the calcium ionophore-induced acrosome reaction

Sperm concentration and motility are poor predictors of the outcome of intrauterine insemination (IUI), hysteroscopic intratubal insemination (HIT), or complete fertilization failure (CFF) in conventional IVF. We investigated whether the calcium ionophore-induced acrosome reaction (AR) constitutes an additional indicator of CFF and pregnancy that is independent of these semen parameters. Infertile couples with no female factor (n=388) and women with tubal obstruction (n=32) were studied: IVF (n=133), ICSI (n=72), HIT (n=245) and IUI (n=61). The percentage of acrosome-reacted sperm in relation to viable sperm was calculated. Receiver operating characteristic curve and multiple logistic regression analyses were used to determine threshold values and the best predictor for CFF and pregnancy. Threshold values of AR for predicting CFF in IVF and pregnancy in IVF and HIT + IUI were 21, 26 and 22% respectively. These values were independent of the conventional semen analysis parameters. CFF was lower (2 versus 20%; P<0.01) and the pregnancy rate was higher (46 versus 24% P<0.05) for those with AR >21% in IVF. CFF and pregnancy rate in ICSI did not differ according to AR. Pregnancy rate was higher for those with an AR >22% for HIT + IUI (23 versus 11% P<0.01). Ionophore-induced AR appears to be a useful indicator in addition to routine semen analysis for selection of patients for treatment with appropriate assisted reproduction procedure.

Prediction of outcomes of assisted reproductive technology treatment by calcium ionophore-induced acrosome reaction

Conventional semen analysis is not a good predictor of successful outcome of in vivo insemination, intrauterine insemination (IUI) or hysteroscopic intra-tubal insemination (HIT), or a predictor of complete fertilization failure (CFF) in conventional IVF (IVF). We investigated whether calcium ionophore induced acrosome reaction provides an additional indicator of pregnancy among various assisted reproduction modalities as well as an indicator of complete fertilization failure in IVF, independent of conventional semen parameters, sperm concentration and motility. prospective study Subjects included infertile couples with no female infertility factors (n=478) and women with tubal obstruction (n=32). Procedures included conventional IVF (IVF): n=148, ICSI: n=72, HIT: n=245, IUI: n=61. They all underwent a standard protocol of history-taking, physical examination and investigations including conventional semen analysis as well as a test of the sperm acrosome reaction following ionophore challenge. Every patient gave an informed consent prior to participating in this study, which was approved by the local Institutional Review Board, Faculty of Medicine. Calcium ionophore induced acrosomal reactivity was assessed in spermatozoa selected by swim-up. Spermatozoa on the slide were subjected to staining with fluorescent isothiocyanate-conjugated pisum sativum agglutinin (FITC-PSA) and with Hoescht 33258. Spermatozoa were considered viable when their heads were unstained or stained only lightly with Hoechst 33258. When the equatorial segment strongly stained with FITC-PSA, the spermatozoon was considered to have reacted. The percentage of acrosome-reacted spermatozoa to viable spermatozoa (%AR) was calculated. At least 300 spermatozoa per sample were examined to determine the %AR. We excluded abnormal or deformed spermatozoa, as well as unclassifiable fluorescence patterns. Multiple logistic regression analysis and receiver-operator characteristic (ROC) curve analysis were performed to determine the best predictive variables and cut-off values in the prediction of fertilization rate and pregnancy in each modality. χ-square analysis was used to compare the different fertilization and pregnancy rates. P<0.05 was considered significant. Cut-off value of %AR for IVF was 21% and the value was independent from the parameters of conventional semen analysis in predicting fertilization rate and pregnancy. Fertilization rate on IVF was higher for those with %AR over 21% compared to that of those with a lower percentage (63.6% vs. 35.4%; p<0.01). The pregnancy rate was also higher (43.1% vs. 18.9%; p<0.01). CFF was lower for those with %AR over 21% (24.5% vs. 4.2%,p<0.01). Fertilization rate, pregnancy rate, and CFF on ICSI did not differ for those with %AR over 21%. Pregnancy rates were higher for those with %AR over 21% than for those with a lower percentage on IUI (28.0% vs. 5.6%, p<0.05) and on HIT (23.9% vs. 6.2%, p<0.01). These data shows that %AR may be a novel parameter independent of conventional semen parameters in choosing assisted reproduction modalities. Thus, patients with acrosomal reactivity below 21% could not achieve pregnancy by IUI, HIT, or IVF with high rates. With reactivity below 21%, a low fertilization rate for initial IVF, ICSI or split fertilization is indicated.

Conventional in vitro fertilization versus intracytoplasmic sperm injection for sibling oocytes in couples with mild oligoteratoasthenozoospermia and couples with normal sperm

Use of intracytoplasmic sperm injection (ICSI) in couples with mild oligoteratoasthenozoospermia decreases the complete fertilization failure rate and may also reduce the embryo cleavage rate. ICSI does not benefit couples with normal sperm.

A strategy for treatment of couples with unexplained infertility who failed to conceive after intrauterine insemination

Couples with unexplained infertility treated unsuccessfully with intrauterine insemination often receive further treatment with IVF or intracytoplasmic sperm injection (ICSI). The aim of this study was to evaluate the frequency of fertilization and fertilization failure with respect to the method of fertilization used, when half of the sibling oocytes were fertilized by conventional IVF and insemination and the remainder by ICSI. Included was the first IVF/ICSI treatment of 248 unexplained infertile couples who had failed to conceive after three IUI cycles. An overall pregnancy rate per embryo transfer of 57% was observed. A significantly better fertilization rate was obtained after ICSI as compared with IVF (68 versus 46%) ( P < 0.005), and total fertilization failure following ICSI and IVF treatment was seen in 4.4 and 25% of the cycles respectively. The group who experienced total fertilization failure after IVF had normal semen parameters, although significantly lower sperm concentration and motility as compared with the entire study group. Transfer of their ICSI-fertilized oocytes subsequently resulted in a pregnancy rate of 49.2% per transfer. The policy of splitting the sibling oocytes can effectively minimize complete fertilization failure while maintaining high chances of achieving a pregnancy. At the same time, the optimal fertilization method for subsequent treatment cycles can be determined.

Oocyte number per livebirth in IVF: were Steptoe and Edwards less wasteful?

Objective: A historical comparison between the number of oocytes required for livebirth in IVF at Bourn Hall Clinic in 1980–1983 and in 2000. Design: Retrospective analysis. Materials and Methods: A series of 847 consecutive long down regulation GnRHa IVF cycles carried out at Bourn Hall Clinic (BHC) between January–December 2000 was reviewed. For the purpose of data analysis, nine cycles in which there was complete failure of fertilization, and 30 cycles in which all embryos were frozen due to risk of OHSS were excluded from the study; the outcome of 808 cycles resulting in fresh embryo transfer was confirmed by follow-up. Standard long down-regulation was accomplished with luteal phase intranasal Nafarelin, 400 micrograms twice daily. After confirmation of downregulation, recombinant-hFSH (Gonal-F(r), Serono) was administered at a starting dose based on age, previous IVF response, weight and baseline laboratory results. The mean patient age was 33.5, with a range of 21–47. Generally, patients aged <35 years started with 150 IU, those aged 35–39 years with 225 IU and aged 40 years or older started with 300 IU or more. HCG was administered when two or more follicles were at least 18 mm (but preferably less than 22 mm) in diameter, coinciding with at least 7mm endometrial thickness and estradiol preferably between 70 pg/ml–140 pg/ml per large follicle. HCG dosage of 10,000 IU was used unless OHSS risk justified 5,000 IU. Luteal phase support was started on the day of oocyte retrieval, in the form of vaginal or rectal Cyclogest(r) (Cox Pharmaceuticals, UK) 400 mg twice daily or Crinone(r) (Serono) 8% vaginally once daily. Two embryos (occasionally 3 in selected cases) were transferred on day 2 or 3 using the Edwards-Wallace soft embryo transfer catheter.The data was tabulated according to age and number of oocytes retrieved. Low Yield (LY) patients were defined as those in whom 1–5 oocytes retrieved, Intermediate Yield (IY) patients had 6–15 oocytes retrieved and High Yield (HY) patients had 16 or more oocytes retrieved. Results: Patients were subdivided into groups by age (< 37 yrs, 38+ yrs), and by oocyte yield (low, intermediate, high). In patients less than 38 years of age, fertilization rates and livebirth deliveries were equivalent, irrespective of the number of oocytes retrieved. Those who yielded Low numbers of oocytes (1–5) required 9.6 oocytes per livebirth, compared with 25.1 and 51.5 in those who yielded Intermediate (6–16) and High (16+) numbers of oocytes. Conclusion: Although we now have more than 20 year’s experience of superovulation for IVF treatment, our results suggest that the efficiency of oocyte utilization has not significantly improved since the early 1980’s. We raise the question of whether milder stimulation regimes will produce the oocyte destined for a livebirth: does collecting fewer oocytes provide a better clinical strategy for oocyte selection than does the harvesting of large numbers of oocytes?