Implications of complete fertilization failure after intracytoplasmic sperm injection for subsequent fertilization and reproductive outcome

With the introduction of intracytoplasmic sperm injection (ICSI), couples with severe male factor infertility have achieved fertilization and clinical pregnancy rates comparable to other in-vitro fertilization (IVF) patients. However, failure of fertilization still occurs in some patients despite the utilization of microsurgical sperm injection techniques. How such fertilization failure after ICSI might impact later ICSI treatment(s) is unknown. In this investigation, couples with complete fertilization failure after ICSI treated from August 1993 to August 1996 were identified (index cycle, n = 21). Additionally, fertilization data from any previous or subsequent infertility treatments were evaluated. Seven patients (33%) had at least one IVF treatment before the index cycle, although no deliveries occurred. Of patients with complete fertilization failure in the index cycle, 48% (n = 10) underwent at least one subsequent ICSI cycle which proceeded to oocyte retrieval. The remainder (n = 11) elected to discontinue treatment. Although six subsequent cycles were cancelled due to poor follicular response (< or = 2 mature oocytes), all patients electing to continue treatment eventually achieved a subsequent embryo transfer. The clinical pregnancy rate per transfer was 45.4% for this group; the delivery and ongoing pregnancy rate per transfer was 36.3%. Review of semen parameters, superovulation characteristics or other clinical parameters during the three study cycles (pre-index, index, and post-index) was not prognostic of fertilization success or reproductive outcomes in later treatments. Fertilization failure with ICSI therefore could not be predicted by prior cycle performance, although total immotility of spermatozoa at time of oocyte retrieval, total teratozoospermia, and low oocyte yield were common characteristics of couples experiencing complete fertilization failure with ICSI. These findings suggest that fertilization failure in one ICSI cycle does not preclude successful fertilization and delivery in a later ICSI treatment.     

Relationship between human in-vitro fertilization and intracytoplasmic sperm injection and the zona-free hamster egg penetration test

The zona-free hamster egg penetration test (HEPT) is widely used for evaluating the fertilizing ability of human spermatozoa. However, the relationship between the HEPT and microassisted fertilization has yet to be determined. To evaluate the efficiency of HEPT in selecting the most appropriate method of in-vitro fertilization (IVF), including intracytoplasmic sperm injection (ICSI) in couples with male factor infertility, clinical laboratory data was analysed retrospectively. The patients were divided into groups according to the sperm penetration index as determined by the HEPT: group A (sperm penetration index = 0), group B (sperm penetration index < 15) and group C (sperm penetration index > or = 15). A total of 405 oocytes were collected and inseminated by conventional methods in 69 couples with male factor infertility. In all, 31 out of 148 (20.9%) oocytes fertilized in group A; 35 out of 117 (29.9%) in group B; and 73 of 140 (52.1%) in group C. The clinical pregnancy rates per transfer in groups A, B and C were 0% (0/13), 0% (0/14) and 25.9% (7/27) respectively. Both the fertilization rate and pregnancy rate in group C was significantly higher than in groups A and B. ICSI was carried out in a total of 57 couples and 334 oocytes in metaphase II stage were manipulated. The normal fertilization (2 pronuclear) rate per oocyte was 65.6 +/- 26.0% (mean +/- SD). Out of 127 oocytes, 76 (59.8%) fertilized in group A, 57 out of 87 oocytes (65.5%) in group B and 86 out of 120 oocytes (71.7%) in group C. Of the 56 transfers, 17 clinical pregnancies were obtained, giving an average pregnancy rate of 30.4% per transfer. The clinical pregnancy rates per transfer in groups A, B and C were 17.4% (4/23), 40.0% (4/10) and 39.1% (9/23) respectively. No significant differences were observed in the fertilization rates or in the pregnancy rates between the three groups. In addition, there were no differences in the fertilization and pregnancy rates between the ICSI and IVF patients in group C. These findings suggest that the results of the HEPT are well correlated with the fertilizing ability of human spermatozoa in the patients treated by conventional IVF. Couples suffering from male factor infertility with a sperm penetration index of < 15 (as determined by HEPT) should consider treatment with ICSI, while those with a sperm penetration index of > or = 15 should attempt conventional IVF.     

A new method for freezing testicular biopsy sperm: three pregnancies with sperm extracted from cryopreserved sections of seminiferous tubule

OBJECTIVE: To determine whether spermatozoa, located in the seminiferous tubules obtained by needle puncture testicular biopsy, could be cryopreserved successfully within the tubules and subsequently be used for in oocyte fertilization via intracytoplasmic sperm injection (ICSI) after the spermatozoa were removed from the thawed tubules. DESIGN: Clinical case series. SETTING: Private IVF unit. PATIENT(S): Six azoospermic patients (four obstructive, two maturation arrest). MAIN OUTCOME MEASURE(S): Survival rate of thawed spermatozoa, fertilization rate of oocytes after ICSI with spermatozoa extracted from thawed tubules and pregnancies. RESULT(S): All six patients had adequate motile spermatozoa extracted from the thawed tubule sections, and all patients achieved fertilization via ICSI with their partner's eggs. The fertilization rate was 46%, compared with 56% obtained in other previous patient cycles using fresh testicular spermatozoa. Three pregnancies resulted from five ETs. CONCLUSION(S): Cryopreservation and subsequent thawing of seminiferous tubules proved to be a simple and successful method for storage of testicular spermatozoa, reducing the need for repetitive testicular biopsies and increasing the likelihood of sperm availability on the day of oocyte retrieval.     

Intracytoplasmic sperm injection as a routine indication in low responder patients

The aim of this study was to determine if a low response to gonadotrophin stimulation could be considered as an indication for intracytoplasmic sperm injection (ICSI). This prospective study included a total of 96 non-male infertile couples with six or fewer retrieved oocytes, who underwent 104 in-vitro fertilization (IVF) cycles between January 1996 and April 1997. They were randomly divided into two groups for fertilization, one by IVF and the other by ICSI. Groups were compared in terms of fertilization rates, fertilization failure, embryo quality, embryos transferred and reproductive outcome. ICSI provided similar fertilization rates per inseminated oocyte (77.7 versus 70.2%) and per obtained oocyte (56.5 versus 58.8%) as IVF. Furthermore, equal numbers (2.2 versus 2.5) and quality of embryos were obtained and comparable pregnancy (21.1 versus 17.3%) and implantation (14.0 versus 11.1%) rates. Neither the number of retrieved oocytes, nor patient age was relevant for the fertilization rates obtained with both techniques. The number of cases with complete fertilization failure was similar in both procedures. We conclude that the technique of fertilization is not related to the reproductive outcome of low responders, and the routine use of ICSI is not indicated.     

Influence of oocyte preincubation time on fertilization after intracytoplasmic sperm injection

During the intracytoplasmic sperm injection (ICSI) procedure, the collected oocytes are incubated until just before ICSI. The ideal preincubation time of oocytes was investigated in 544 treatment cycles. Oocyte retrieval was carried out 35 h after human chorionic gonadotrophin administration. Oocytes were cultured for between 1 and 11 h before ICSI. Embryo transfer was performed 48 h after oocyte collection. The survival, fertilization and cleavage rates of injected oocytes indicated no statistically significant differences between oocytes preincubated for different lengths of time. The proportion of good-quality embryos (grades 1 and 2) was lower at 9-11 h of preincubation time than for all the other preincubation times (P < 0.001). No statistically significant differences were detected in the pregnancy rate between each group (mean: 15.9%), although the pregnancy rate at 9-11 h of preincubation time appeared to be low (7.7%). These results suggest that the oocyte retained sufficient potential for fertilization between 1 and 9 h after oocyte collection in ICSI. For the researchers who practise more complex ICSI procedures than IVF, it would be convenient to be able to perform ICSI at any time between 1 and 9 h after oocyte collection.     

In vitro fertilization in women age 40 and older: the impact of assisted hatching

PURPOSE: To assess the impact of assisted hatching on in vitro fertilization (IVF) outcome in women age 40 and older. METHODS: A retrospective analysis was performed to compare 28 cycles of IVF without assisted hatching to 38 cycles of IVF with assisted hatching. All patients in both groups were age 40 or older and the mean age was similar. RESULTS: The delivery rate per oocyte retrieval was significantly higher in the assisted hatching group (18/38; 48%) compared to the nonhatched controls (3/28; 11%, P = 0.0003). The implantation rate of hatched embryos (40/175; 22%) was clearly enhanced, compared to the nonhatched embryos (7/126; 6%, P < 0.001). The fertilization rate, number of oocytes and the number of embryos per patient were comparable in the two groups. CONCLUSIONS: Assisted hatching dramatically improves embryonic implantation and term pregnancy rates in women age 40 and older undergoing IVF.     

Outcome of pregnancy in IVF-ET cycle at Ramathibodi Hospital

As assisted reproductive technology is being developed, in vitro fertilization and embryo transfer (IVF-ET) are the treatments of choice for many infertility problems. The outcome of pregnancies achieved by IVF-ET is different from that of spontaneous pregnancies. In this retrospective study, the outcome of pregnancies from 400 IVF treatment cycles performed from October 1991 to October 1994 were reported. There were 80 pregnancies (20% per oocyte retrieval, 21.9% per embryo transfer) with an increased rate of abortion (30%), multiple pregnancy (20%), ectopic pregnancy (6.25%), heterotopic pregnancy (1.25%), preterm delivery (11.8%), low birth weight (35.8%) and cesarean section (62.7%). This study shows that the complication rate of pregnancies from IVF-ET cycles was higher than that found in spontaneous pregnancies. Some complications such as multiple pregnancies may be prevented by limiting the number of transferred embryos. From this study, all IVF-ET pregnancy should be considered as high risk pregnancies.     

An interview with Sue Hall Esleck. Interview by Connie R. Curran

The present report covers the results of a 38-month period in which 2853 consecutive intracytoplasmic sperm injection (ICSI) cycles were performed in 1953 couples. These couples were afflicted with male factor infertility and had at least one previous failed conventional in vitro fertilization (IVF) treatment cycle. In other couples, the husband had semen parameters incompatible with conventional IVF or suffered from excretory or secretory azoospermia where it was possible to recover spermatozoa by microsurgical epididymal sperm aspiration (mesa) or by testicular sperm extraction (tese) procedure. Overall, the 2-PN fertilization rate was 62% per retrieved metaphase II oocyte and 70% per successfully injected metaphase II oocyte. Embryo transfer was performed in 91% of started cycles. The cumulative pregnancy rate (positive HCG) was 34% per started ICSI treatment and 37% per embryo transfer.     

Excimer laser phototherapeutic keratectomy

OBJECTIVE: To test the effect in an assisted pregnancy program of an agent known to enhance sperm motility and oocyte penetration ability. DESIGN: Prospective with internal control. SETTING: Hospital clinic. PATIENTS AND INTERVENTIONS: Forty-two oocytes obtained from women undergoing IVF were inseminated with their husband's sperm washed, incubated, and capacitated in Earle's medium supplemented with 1 mM, 2.5 mM, or 5 mM 2-deoxyadenosine (2-DXA). The outcome of insemination was compared with those of 234 control oocytes from the same women that were inseminated with husband's sperm washed in 2-DXA-free medium. 15, 14, and 13 oocytes were inseminated with sperm washed in 1 mM, 2.5 mM, and 5 mM 2-DXA, respectively. RESULTS: Fertilization rates in the respective groups were 93%, 85.7%, and 85.5%. These were higher than the 70.1% fertilization rate in the control group, but only statistically higher (P < .002) in the 1 mM 2-DXA group. Embryonic development in all three 2-DXA groups was comparable to the controls. CONCLUSION: It is suggested that the value of sperm motility enhancing agents requires further evaluation in assisted pregnancy programs.     

Human menopausal gonadotropin during in vitro maturation of human oocytes retrieved from small follicles enhances in vitro fertilization and cleavage rates

OBJECTIVES: To compare the IVF rates of oocytes retrieved from small follicles (< 2 mL in volume) with those of oocytes retrieved from large follicles and to test the effect of adding gonadotropins to the IVF medium on the fertilization rates of oocytes from small follicles. DESIGN: Oocytes were retrieved with endovaginal ultrasound (US) guidance from patients undergoing infertility treatment in our IVF program. Oocytes were grouped according to the volume of the originating follicle and subjected to our routine procedure for IVF. HMG was added to the IVF medium for some of the oocytes from small follicles. SETTING: Toronto Fertility and Sterility Institute is affiliated with the University of Western Ontario and University of Toronto and is equipped for RIA, endovaginal US monitoring and oocyte retrieval, and for processing and culturing gametes and embryos. PATIENTS: Infertile patients admitted to our IVF program. INTERVENTIONS: Patients underwent ovarian stimulation with hMG before oocyte retrieval. No other interventions were introduced to the processing and culturing the gametes and embryos except the addition of hMG to the medium of some of the small follicle-originated oocytes with the informed consent from the patients. MAIN OUTCOME MEASURES: Rates of fertilization, cleavage of the fertilized embryos before replacement, and meiotic status of some of the oocytes from small follicles. RESULTS: Most of the oocytes from small follicles did not complete the first meiotic division; they had low rates of fertilization and cleavage compared with oocytes from large follicles, and these rates were improved by the addition of hMG to the IVF medium. CONCLUSIONS: Oocytes from small follicles are probably less mature and require a more physiological environment to achieve normal rates of fertilization and cleavage.     

Fertilization and in vitro development of cryopreserved human prophase I oocytes

OBJECTIVE: To determine the potential for in vitro maturation, fertilization, and cleavage after cryopreservation of immature, prophase I human oocytes. DESIGN: Immature oocytes obtained in excess of the number required by the patient were randomized and cryopreserved at the prophase I stage or cultured as control. After thawing and maturation in vitro, test and control oocytes were inseminated with husband's sperm and evaluated for fertilization and cleavage in vitro. SETTING: In vitro fertilization program. PATIENTS: Consenting patients undergoing controlled ovarian hyperstimulation for the purposes of IVF. MAIN OUTCOME MEASURES: Rates of maturation to metaphase II, fertilization, and cleavage were compared between control and cryopreserved oocytes. RESULTS: Upon thaw, 58.5% (72/123) of prophase I oocytes were viable. Control oocytes demonstrated a 74.8% (98/131) maturation rate to metaphase II, a 56.5% (52/92) fertilization rate, and an 11.5% (6/52) blastocyst rate. Cryopreserved oocytes showed a 83.3% (60/72) rate of maturation, a 57.7% (30/52) fertilization rate, and a 3.3% (1/30) blastocyst rate. No significant differences were noted between any of these parameters. CONCLUSIONS: These results demonstrate that prophase I oocytes from stimulated IVF cycles are able to survive cryopreservation and resume meiosis to achieve full nuclear maturation post-thaw. In addition, cryopreserved oocytes retain the same capacity for fertilization and development as control oocytes.     

Extracts from various mite species contain cross-reactive and noncross-reactive IgE epitopes. A RAST inhibition study

PURPOSE: A low pregnancy rate in in vitro fertilization (IVF) patients of advanced maternal age may be caused by aneuploidies originating from non disjunction in the first or second meiotic divisions. We introduced genetic testing of oocytes by sampling and fluorescent in situ hybridization (FISH) analysis of the first and second polar bodies, to avoid fertilization and transfer of aneuploid oocytes in IVF patients of advanced maternal age. METHODS: Three hundred and sixty-three IVF patients 34 years and older participated in the study. Using micromanipulation procedures, the first and second polar bodies were removed following their extrusion from the oocytes and studied by FISH, using probes specific for chromosomes 13, 18, and 21 to detect oocytes with common aneuploidies. RESULTS: Of a total of 538 IVF cycles, 3250 oocytes were available for FISH analysis, with conclusive FISH results in 2742 oocytes (84.3%). As many as 1102 (40%) of oocytes were predicted to be aneuploid and not transferred. Of 1640 embryos predicted to be normal, 1145 were transferred in 467 treatment cycles, resulting in 107 pregnancies (23%), from which 67 healthy children have been born, 32 pregnancies spontaneously aborted, and 15 pregnancies are ongoing after being confirmed normal by prenatal diagnosis. CONCLUSIONS: Preimplantation diagnosis by first- and second-polar body FISH analysis allows us to avoid the age-related risk of common aneuploidies in IVF patients of advanced maternal age.     

An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer

To assess if the waist:hip ratio (WHR) is associated with the pregnancy rate (PR) in in-vitro fertilization (IVF) and embryo transfer, waist and hip girths, in addition to height, weight, body mass index (BMI), indications for IVF, PR and other related variables, were measured in 220 women undergoing IVF-embryo transfer. Three variables were significantly negatively associated with PR; high age, smoking and WHR >0.80. Women with WHR between 0.70-0.79 had a PR of 29.9% as compared to 15.9% in women with WHR >0.80 [odds ratio 0.42, 95% confidence interval (CI) 0.2-0.9, P = 0.03]. There were no correlations between BMI and PR, nor were there any significant differences for the indications for IVF-embryo transfer, number of oocytes or oocyte fertilization rate, cleavage rate and number of embryos transferred. The association between a low PR and WHR >0.80 remained unchanged after adjustment for age, BMI, smoking, indication for IVF, parity and number of embryos transferred. In IVF-embryo transfer, fertilization is a laboratory and clinically controlled process, until the embryo is transferred to the uterus. Possible reasons for our finding of a decreased PR in women with an android body fat distribution include a different endocrinological and biochemical milieu for the oocyte in the growing follicle, oocytes of poor quality, or endometrial changes due to hormonal dysfunction.     

The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization--a randomized study

A group of 78 infertile women, diagnosed as having tubal factor infertility only, was enrolled in a prospective, randomized study conducted to determine whether the addition of different doses of glucocorticoids to the protocol of ovulation induction for in-vitro fertilization (IVF) would be beneficial. Oocyte numbers, percentage of fertilization, oestradiol, luteinizing hormone and follicle stimulating hormone serum concentrations, number of embryo transfers and pregnancy rate were evaluated. Compared to control cycles (group A; n = 24), the addition of 0.5 mg (group B; n = 27) of 1 mg dexamethasone (group C; n = 27), combined with the protocol of programmed oocyte retrieval for IVF patients in the study, demonstrated equivalent results. The mean numbers of oocytes retrieved were 10.8 +/- 3.9 in the control group, compared to 11.2 +/- 4.0 in group B and 10.5 +/- 3.6 in group C. The fertilization rates were 69 +/- 21, 66 +/- 18 and 70 +/- 15% respectively. The pregnancy rates were 20, 16 and 20.8% respectively. The addition of up to 1 mg dexamethasone daily to the protocol of ovulation induction for oocyte retrieval did not improve the overall IVF-embryo transfer outcome in patients with tubal factor infertility.     

An oocyte donation program with goserelin down-regulation of voluntary donors

BACKGROUND: In ovum donation programs oocytes can be requested from infertile women going through an in vitro fertilization cycle. Currently, when embryos can be cryopreserved, these donors have virtually disappeared. Instead, most donors have been healthy fertile volunteers willing to go through an IVF attempt solely for the purpose of donating all oocytes. METHODS: Sixty-four patients had 93 started cycles of oocyte donation from 59 donors. Twenty recipients had primary ovarian failure, 24 had secondary ovarian failure, 15 had had repeated failures in earlier IVF attempts and five were carriers of genetic diseases. The donors were 51 healthy volunteers recruited through the press. Eight patients from an IVF program donated excess oocytes. Donors were not paid and their mean age was 30 years. To minimize discomfort of the treatment, a long-acting GnRH-agonist, goserelin, was used for down-regulation. RESULTS: The pregnancy rate per transfer with fresh embryos was 28.4% (23/81) and with frozen-thawed embryos, 17% (3/18). Twenty-one healthy infants have been born including one set of triplets and three sets of twins. Nine pregnancies ended in abortion and one in intrauterine fetal death. The most common complications of pregnancy were pre-eclampsia and pregnancy-induced hypertension (41.2%, 7/17). Ten of 17 patients delivered by cesarean section (58.8%). CONCLUSION: It was possible, through the press, to obtain highly motivated oocyte donors, who go through IVF treatment solely for altruistic reasons. Oocyte recipients appear to have many complications in their pregnancies. Until more data are available, these patients need a high standard of obstetric care.     

Pregnancy and birth after high serum progesterone concentrations during the follicular phase in an in-vitro fertilization cycle with gonadotrophin-releasing hormone agonist suppression

This case illustrates the possibility of achieving a pregnancy and birth when elevated progesterone concentrations (> 4 ng/ml) are present during the follicular phase (from 6 days before human chorionic gonadotrophin injection) of a gonadotrophin-releasing hormone agonist/menotrophin cycle for in-vitro fertilization (IVF). The present patient underwent three IVF/embryo transfer cycles in which progesterone concentrations were repeatedly increased from the midfollicular phase onwards. A pregnancy was achieved after the first IVF attempt but ended in a miscarriage in the 19th week of gestation. During the second IVF attempt an endometrial biopsy taken on the day of oocyte retrieval revealed an endometrial advancement of 2 days. A successful pregnancy and birth was again achieved after the third IVF attempt although progesterone concentrations were considerably increased from 6 days before the ovulatory stimulus.     

One thousand initiated cycles of in vitro fertilization in women > or = 40 years of age

OBJECTIVE: To evaluate the results of IVF in women > or = 40 years of age using their own oocytes. DESIGN: Retrospective study. SETTING: Wolfson and Royal Masonic in vitro fertilization units, London, United Kingdom. PATIENT(S): A total of 1,087 IVF cycles were started in women > or = 40 years of age. INTERVENTION(S): Medical records of patient outcomes were reviewed. MAIN OUTCOME MEASURE(S): Clinical pregnancy, miscarriage, and delivery rates. RESULT(S): Of the 1,087 cycles started in 471 women > or = 40 years of age, 842 reached oocyte retrieval (77.5%) and 702 had embryos transferred (64.6%). The pregnancy rate (PR) was significantly lower in women > or = 40 years of age than in a control group of women <40 years of age (11.3% versus 28.2%). It decreased sharply in women >42 years of age, and no women >45 years of age had a child. Women > or = 40 years of age were more likely to miscarry (27% versus 12.7%). When only one embryo was available for transfer, the PR was 3.3%. When >2 embryos were available for transfer, the PR was similar whether 2 or 3 embryos were replaced. No triplet pregnancy occurred. Women > or = 40 years of age achieved a cumulative PR of 30% after three cycles with a cumulative "take home baby" rate of 21%. CONCLUSION(S): In vitro fertilization is a reasonable treatment for women <45 years of age using their own gametes. Those with a "good response" in their first attempt may be encouraged to complete three cycles with an acceptable chance of conception.     

Dizygotic twin pregnancy after intracytoplasmic sperm injection of 1 day old unfertilized oocytes

We report on a case where late intracytoplasmic sperm injection (ICSI) on unfertilized oocytes after standard in-vitro fertilization (IVF) cycles resulted in a dizygotic twin pregnancy. Fifteen oocytes were harvested from a patient with a history of salpingotomy. After a single cycle of IVF, only one oocyte showed two pronuclei. Subsequently ICSI was performed on six unfertilized metaphase II oocytes, and three of these oocytes showed two pronuclei. Three fertilized embryos were transferred (two derived from ICSI and one from IVF). A normal twin pregnancy resulted, and after delivery of two healthy boys the twins were confirmed to be dizygotic by DNA analysis of several loci. We conclude that at least one of the embryos was derived from the reinsemination by 'second day ICSI'.     

Clinical outcome of cryopreserved human pronuclear stage embryos resulting from intracytoplasmic sperm injection

OBJECTIVE: To compare the survival rate and pregnancy rate (PR) of embryos from intracytoplasmic sperm injection (ICSI) or conventional IVF, which were cryopreserved at the pronuclear stage in cycles where fresh transfer was deferred. DESIGN: Comparative observational study. SETTING: University-associated IVF center. PATIENT(S): Ninety-nine patients who deferred ET and had all their embryos cryopreserved at the pronuclear stage after 153 oocyte retrievals. Thirty-nine patients had their oocytes inseminated by ICSI and 60 patients had conventional IVF insemination. INTERVENTION(S): All embryos were frozen-thawed at the two pronuclear stage and allowed to cleave for 2 days before transfer. MAIN OUTCOME MEASURE(S): Survival rate (morphologically intact after thaw), cleavage rate (cleaved by time of transfer), and the clinical PR after frozen ET. RESULT(S): In the ICSI group, 205 embryos were thawed for use in 57 frozen ETs; in the IVF group, there were 527 embryos thawed for use in 149 frozen ETs. There was no significant difference in any of the outcome measures by insemination method: survival rates (ICSI, 93.2%; IVF, 94.8%); cleavage rates (ICSI, 95.2%; IVF, 94.7%), and clinical PR (ICSI, 14.0%; IVF, 17.4%). CONCLUSION(S): Pronuclear embryos resulting from ICSI can be cryopreserved successfully, thawed, and the survival rate and PR are comparable to conventional IVF.     

Continuing the debate on empty follicle syndrome: can it be associated with normal bioavailability of beta-human chorionic gonadotrophin on the day of oocyte recovery?

This paper describes our experience with four ovarian stimulation in-vitro fertilization (IVF) cycles in which we failed to retrieve oocytes despite normal bioavailability of beta-human chorionic gonadotrophin (beta-HCG) in patients' blood 35 h after HCG administration. In three cases, the oocyte recovery procedure was interrupted, a second dose of HCG was administered and 24 h later mature oocytes were collected from two of the patients. In the first case, the three metaphase II oocytes collected fertilized after intracytoplasmic sperm injection (ICSI) and two cleaved grade three embryos were transferred but pregnancy did not ensue. In the second case, six out of eight metaphase II oocytes fertilized and cleaved following ICSI, leading to transfer of one grade two and two grade three embryos. This resulted in a clinical pregnancy which at the time of this report is ongoing. A similar rescue protocol was used for the third case who had empty follicle syndrome (EFS) in her previous treatment cycle but only cumulus-corona complexes were aspirated. Five additional patients who had EFS before instituting pregnancy diagnostic test screening have had further treatment cycles in which oocytes were collected but pregnancy did not ensue. We conclude that normal bioavailability of beta-HCG on the day of oocyte recovery does not exclude the diagnosis of EFS. EFS does not predict a reduced fertility potential in future cycles, although it may recur due to a biological abnormality in the availability of mature oocytes that are retrievable. In such patients, oocyte donation may offer the chance of achieving a pregnancy.