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In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure.

OBJECTIVE: To determine whether the performance of intracytoplasmic sperm injection (ICSI) in cases of unexplained infertility and of borderline semen parameters can prevent fertilization failure. DESIGN: Prospective cohort study. SETTING: Hospital-based assisted reproductive technology program. PATIENT(S): Sixty couples with unexplained infertility (group 1) and 50 couples with borderline semen (group 2). INTERVENTION(S): Conventional IVF and ICSI were performed on sibling oocyte cumulus complexes. MAIN OUTCOME MEASURE(S): Rate of fertilization according to patient diagnosis. RESULT(S): The fertilization rate per oocyte cumulus complex in couples with unexplained infertility (group 1) was significantly higher with ICSI (65.3%) compared with IVF insemination (48.1%). Fertilization rates per OCC in couples with borderline semen (group 2) were not significantly different between ICSI (58.1%) and IVF (56.7%). In group 1, failure of fertilization after IVF insemination occurred in 10 of the 60 couples (16.7%) and in none with ICSI. In group 2, 2 of 50 couples (4.0%) failed fertilization by IVF, and 1 (2.0%) failed with ICSI. No couple in group 2 failed both IVF insemination and ICSI. CONCLUSION(S): In couples with unexplained infertility, a higher fertilization rate was achieved through ICSI compared with conventional IVF. No such benefit could be demonstrated for couples with borderline semen parameters. The use of ICSI rescued 12 of 110 cycles (10.9%) where IVF failed. Adoption of the ICSI-IVF insemination split in cases of unexplained infertility may help eliminate fertilization failures.

Cohort Studies↗

Previous fertilization failure with conventional in vitro fertilization is associated with poor outcome of intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the outcome of intracytoplasmic sperm injection (ICSI) in patients with a history of fertilization failure with conventional IVF. DESIGN: Retrospective analysis of 2 years of clinical experience with ICSI. SETTING: Clinical IVF-ET program in a tertiary care referral center. PATIENT(S): The results of ICSI performed between January 1995 and December 1996 were compared between patients with normal semen parameters and a history of fertilization failure (< 20% of oocytes) with conventional IVF and patients with male factor infertility. INTERVENTION(S): In vitro fertilization with ICSI. MAIN OUTCOME MEASURE(S): Parameters examined included oocyte survival, fertilization, embryo cleavage, implantation rates, and clinical pregnancy rates. RESULT(S): Fertilization was achieved with ICSI for all patients during the study period. Although oocyte survival and fertilization did not differ between groups, the pregnancy and implantation rates for patients with a history of idiopathic fertilization failure (20% and 6%, respectively) were significantly lower than those for other patients undergoing ICSI (47% and 22%, respectively). CONCLUSION(S): The outcome of ICSI varied depending on the indication for treatment. Patients who had a history of failed or poor fertilization in vitro with apparently normal semen parameters had significantly lower pregnancy and implantation rates than did patients with either obstructive azoospermia or impaired semen quality.

Adult↗

Numerical dose-compensated in vitro fertilization inseminations yield high fertilization and pregnancy rates.

OBJECTIVE: To evaluate in cases with morphologically abnormal sperm whether fertilization and pregnancy rates are increased by normalizing the number of sperm inseminated and whether biomarkers can identify cases of reduced or failed fertilization. DESIGN: Prospective studies of sperm morphology and function. SETTING: University hospital assisted human reproduction program. PATIENT(S): Partners of 308 women undergoing IVF. INTERVENTION(S): Motile sperm populations were assessed for sperm head morphology, for surface receptors for mannose and progesterone binding, and the ability to undergo a free mannose-induced acrosome reaction. Zinc in seminal plasma was determined by atomic absorption spectroscopy. MAIN OUTCOME MEASURE(S): Sperm morphology was associated with fertilization and clinical pregnancy rates. Biomarker analyses were correlated with fertilization rates using Kruskal-Wallis tests, chi2 tests, and Spearman rank order correlations. RESULT(S): Fertilization and pregnancy rates after numerical dose compensation inseminations were indistinguishable between men with differing percentages of normal sperm. Biomarker deficits were identified irrespective of sperm head morphology in 96% of cases of reduced or failed fertilization. CONCLUSION(S): Fertilization and pregnancy rates in cases of abnormal morphology are optimized by inseminating at least 25,000 sperm/mL with normal acrosomes. Reduced or failed fertilization can be predicted by testing for molecular deficits in mannose receptor expression and mannose-stimulated acrosome loss.

Biomarkers↗

Follicle-stimulating hormone treatment for men with idiopathic oligoteratoasthenozoospermia before in vitro fertilization: the impact on sperm microstructure and fertilization potential.

OBJECTIVE: To assess the effect of FSH on sperm fertilization potential and sperm intracellular structure in men with oligoteratoasthenozoospermia and a proven low fertilization rate in IVF. DESIGN: Prospective, randomized, partial crossover study. SETTING: IVF Unit, Golda Campus, Rabin Medical Center, Petah Tikva, Israel. PATIENT(S): Forty normogonadotropic, normogonadal men with oligoteratoasthenozoospermia and at least one previous IVF attempt in which fertilization failed or the fertilization rate was <30%. INTERVENTION(S): The men were randomly assigned to treatment with daily injections of 75 IU of FSH or 150 IU of FSH for at least 60 days before IVF treatment. A control group of men underwent an IVF cycle without treatment and then were randomly assigned tojoin group 1A or 1B for an additional IVF cycle with treatment. MAIN OUTCOME MEASURE(S): LH, FSH, and testosterone levels during FSH treatment, evaluation of ultramorphologic changes in sperm by electron microscopy, and comparison of fertilization rates in the control and study groups. RESULT(S): After treatment with 75 IU or 150 IU of FSH, the mean fertilization rates were 19.7% and 20.5%, respectively, compared with a 5.8% fertilization rate in the study control cycles. CONCLUSION(S): Prolonged treatment with FSH results in a significant increase in fertilization rates. This effect may be related to improvements in subcellular components of the sperm.

Acrosome↗

In vitro maturation and fertilization of immature oocytes: a comparative study of fertilization techniques.

PURPOSE: Our purpose was to investigate the factors influencing maturation and fertilization of immature oocytes. METHODS: Immature oocytes were obtained from women undergoing cesarean section. They were cultured in the maturation medium either with or without cumulus cells. After maturation to metaphase II, they were randomly fertilized by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). RESULTS: After incubation for 48 hr, 441 oocytes (42.8%) reached metaphase II. Among them, 56.6% of cumulus-enclosed oocytes, but only 29.2% of denuded oocytes, reached metaphase II. Of the 289 cumulus-enclosed oocytes, the fertilization rates by IVF and ICSI were 56.3 and 84.1%, respectively (P < 0.01). Of the 152 denuded oocytes, the fertilization rates by IVF and ICSI were 39.5 and 84.5%, respectively (P < 0.01). The cleavage rates, however, were similar. CONCLUSIONS: Cumulus cells are beneficial in the maturation of human oocytes in vitro and that ICSI increases the fertilization rate for the in vitro matured oocytes. The developmental potential of the fertilized oocytes, however, is similar irrespective of the fertilization method or the presence or absence of cumulus cells.

Adult↗

Functional capacity and fertilizing longevity of frozen-thawed scimitar-horned oryx (Oryx dammah) spermatozoa in a heterologous in vitro fertilization system.

This study was conducted to determine if cryopreservation and thawing reduces the quality of scimitar-horned oryx spermatozoa and thus might be responsible for sub-optimal artificial insemination (Al) efficiency. Functional capacity of frozen thawed oryx spermatozoa was compared in a heterologous bovine in vitro fertilization (IVF) system after being prepared by four methods. Fertilizing longevity was also assessed after thawing and pre-incubating spermatozoa for 12 or 24 h before IVF. Sperm characteristics (viability, morphology, acrosomal and capacitation status) were superior for samples prepared by Percoll centrifugation and standard swim-up compared with microdrop swim-up and wash methods. Regardless of variation in sperm characteristics over time, fertilization success and embryo development were high and did not differ among treatments. Fertilization and cleavage success for spermatozoa pre-incubated for 12 h before IVF were comparable with that achieved with non-incubated spermatozoa. Even 24 h after thawing, spermatozoa were capable of fertilizing oocytes, but percentage fertilization and embryo cleavage were significantly lower than for spermatozoa pre-incubated for 12 h. Overall, functional capacity of oryx spermatozoa after thawing appears comparable with that of domestic bull spermatozoa. When used for Al, frozen-thawed oryx spermatozoa should be capable of fertilizing oocytes in females ovulating 12 or even 24 h after insemination, providing sperm transport mechanisms are adequate. The functional capacity and fertilizing longevity of oryx sperm after thawing is high, and therefore unlikely to be responsible for decreased Al efficiency in the scimitar-horned oryx.

Animals↗

Polyploidy and failed fertilization in in-vitro fertilization are related to patient's age and gamete quality.

A review of 392 cycles of in-vitro fertilization (IVF) was carried out in order to identify whether any factors such as sperm concentration at insemination, sperm motility or morphology, oocyte grading, number of oocytes retrieved, patient age, follicular stimulation protocols or duration of follicular growth, could be associated with the incidence of polyploidy or completely failed fertilization. The majority of polypronuclear fertilizations occurred in mature oocytes and in patients < 37 years of age and the incidence of polyploidy was strongly associated with fertilization and pregnancy rates. Fertilization rates were highest with mature oocytes. A significant linear trend was observed with failed fertilization and sperm concentration, morphology and motility. High rates of failed fertilization were found in patients > 37 years of age and with one to five oocytes retrieved. No significant difference was seen in stimulation protocols and oocyte grading between oocytes that fertilized and those that did not. Cycles with good sperm morphology and motility, the presence of mature oocytes, the retrieval of a large number of oocytes and younger maternal age seem to provide the best chance for IVF success.

Adult↗

The indirect immunobead test for seminal antisperm antibodies and fertilization rates at in-vitro fertilization.

A series of 183 patients with positive indirect immunobead tests on semen was studied to determine the correlation in semen between specific antibody types, binding sites, antibody concentration, and fertilizing ability. IgM was present in only 44 ejaculates and was present in sufficient quantity to cause significant binding to immunobeads (i.e. >20% of motile donor spermatozoa) in only three of them. There was no correlation between the percentages of motile donor spermatozoa that bound IgA and IgG immunobeads but the two classes of beads generally bound to the same region of the spermatozoa. A total of 63 couples went on to attempt in-vitro fertilization (IVF) treatment, all with mature eggs recovered. Of these mature eggs, 44% were fertilized and cleaved normally in comparison to 68% in a group of patients with tubal disease. Fertilization rates in individuals followed a bimodal distribution with a substantial number of couples experiencing zero or very poor rates (0-20%), the mode for the remainder lying between 60 and 80%. The fertilization rate tended to decrease as the amount of antibody increased. The percentage of donor spermatozoa that bound to immunobeads, taken as the greater of IgA and IgG, was selected by logistic regression as a significant predictor of poor fertilization (rate <=25%). The predictive power of the equation was improved by including the motile normal sperm concentration but the equation could only account for a small proportion of the total variation in fertilization rate. The presence of antibodies to the sperm head was highly correlated with the antibody concentration but was not selected as a predictor of fertilization. We conclude that the nature of the antigen against which the seminal antisperm antibody is directed may be as important as the antibody concentration in affecting sperm function. There seems to be little practical value in measuring IgM in seminal plasma.

Adult↗

Prediction of fertility by centrifugal countercurrent distribution (CCCD) analysis: correlation between viability and heterogeneity of ram semen and field fertility.

The prediction of the fertilizing ability of a sire or a given insemination dose is a primary aim in the field of artificial insemination. Centrifugal countercurrent distribution analysis (CCCD) was used to determine the relationship between some sperm parameters and the in vivo fertility rate obtained with the same sample after cervical artificial insemination. A total of 522 ewes from 26 different farms was inseminated with 53 ejaculates obtained from 25 mature Rasa aragonesa rams. Semen was diluted to 1.6 x 10(9) cells ml-1 and doses of 0.25 ml were prepared and kept at 15 degrees C until used for insemination. The same ejaculates were used for analysis of standard semen parameters and CCCD analysis. Sperm motility, concentration and viability were determined before and after CCCD. Post-CCCD parameters were derived from the analysis of the profile obtained after CCCD. The recovered viability showed the highest correlation with fertility, especially in the central chambers (V2), r = 0.415, P < 0.005). The ejaculate heterogeneity also showed a positive correlation with field fertility (r = 0.23), with a tendency towards significance (P < 0.1). The mean fertility value of all ejaculates used in this study was 46.75%, ranging from 12.5% to 75.0%. Ejaculates were classified into two categories according to their fertility: higher and lower than the mean value. Only the viability recovered in the central chambers (V2) was a parameter with a predictive capacity to discriminate between the two groups (P < 0.05). A predictive equation for field fertility with a correlation coefficient r = 0.488 and a very high level of significance (P < 0.005) was deduced by multiple analysis: PF = 6.02 + 0.069V2 + 0.315H (where PF is predictive fertility, V2 is the recovered viability in the CCCD profile central chambers and H is heterogeneity).

Animals↗

Heifer fertility and its relationship with cow fertility and production traits in Holstein dairy cattle.

Breeding receipts from three AI units were merged with Ontario Dairy Herd Improvement Corporation and Record of Performance production records. Data comprised 53,705 heifer, 41,253 lactation 1, 14,688 lactation 2, and 3054 lactation 3 records by daughters of 2150 sires represented in 15,877 herd-year-seasons of birth. Three measures of heifer fertility, three measures of cow fertility, and three measures of production were investigated. Measures of heifer fertility were ages at first and last breeding and number of inseminations per conception. Cow fertility traits were days from calving to first breeding, days open, and number of inseminations per conception. Production traits were breed class average milk, breed class average fat, and fat percentage. Relationships among these nine traits for the first three lactations were estimated using a maximum likelihood multiple-trait procedure. The linear mixed model for each trait included fixed effects of herd-year-season of birth and genetic groups of sire and the random effect of sire. Transformations of the data for nonnormality had no influence on the estimates of genetic and phenotypic parameters. The heritability of .12 for age at first insemination, which was higher than other heifer fertility traits, indicated that selection would result in genetic response. Genetic and phenotypic correlations between heifer fertility and cow fertility and production traits in all three lactations were not different from zero. There was no genetic antagonism between fertility and subsequent production traits.

Animals↗

[Comparative study of the morpho-functional features of the sperm of fertile and infertile men and their relation to fertilizing ability].

The recent advances in assisted reproduction procedures have helped to the better understanding of the female reproductive physiology and pathology, however, male infertility remains as a poor explained medical problem, nevertheless it occurs in almost 50% of infertile couples. Oligoasthenozoospermia is one of the more common causes of male infertility, therefore we measured in 10 patients with this diagnosis and in 10 fertile euspermic men, besides the parameters included in the standard semen analysis, the quantitative motility (photography method), capacitation-acrosome reaction and the sperm ability to fertilize zona-free hamster oocytes, with the aim to correlate the morphofunctional characteristics of the male gametes with their fertilizing capacity. The results showed significant differences in every parameter studied, including the correlation analysis. In relation with the in vitro induction of the acrosome reaction in both groups, we found significant correlations of the sperm fertilizing ability and the progressive sperm motility with this parameter (fertile group: RS = 0.834, P less than 0.005 & RS = 0.612, P less than 0.05; infertile group: RS = 0.986, P less than 0.001 & RS = 0.536, P less than 0.05 respectively), nevertheless the sperm rate which completed this process was low in relation to the total sperm population even in the fertile men (9.4 +/- 2.0% & 4.4 +/- 2.5% acrosome reacted cells after 18 h of incubation, in the fertile and infertile males respectively). The results also showed the presence of fully capacitated spermatozoa in both groups, since they penetrated the zona-free hamster eggs and decondensed their chromatin (73.9 +/- 13.4% & 10.4 +/- 7.7% penetrated eggs in the euspermic and oligoasthenozoospermic individuals respectively), however, the spermatozoa from the oligoasthenozoospermic men showed low polyspermy indexes too (0.1 penetrated spermatozoa/inseminated oocyte). In this last group we found, in addition, that the mean sperm velocity and the abnormal sperm morphology rate showed significant correlations with the fertilizing ability of the male gametes too (RS = 0.986, P less than 0.005 & RS = -0.942, P less than 0.005. respectively). These data allow us to suggest that before an infertile man is involved in any assisted reproduction program, the presence of possible morphofunctional alterations in the spermatozoa be analyzed, with the aim to be able to make a better prognosis about the success with these patients.

Acrosome↗

The fertility-inhibiting effects of the intermediate fertility variables.

Based on the application of an aggregate reproductive model, this study demonstrates that a small number of intermediate fertility variables are responsible for most of the variation in fertility levels of populations. Four variables--proportion married, contraception, induced abortion, and postpartum infecundability--are generally the most important determinants of fertility; the other intermediate factors are of less interest except in unusual circumstances. These four factors explain 96 percent of the variance in the total fertility rate in a sample of 41 populations that include developing and developed countries as well as historical populations. In the last section, the average fertility effect of the principal intermediate fertility variables is estimated for groups of contemporary populations with different total fertility rates.

Abortion, Induced↗

Completing the fertility transition in the developing world: The role of educational differences and fertility preferences.

This study summarizes patterns of educational differentials in wanted and unwanted fertility at different stages of the fertility transition. The data are from Demographic and Health Surveys in 57 less developed countries. As the transition proceeds, educational differentials in wanted fertility tend to decline and differentials in unwanted fertility tend to rise. An assessment of fertility patterns in developed and less developed countries with low fertility concludes that these differentials are likely to remain substantial when less developed countries reach the end of their transitions. This conclusion implies that the educational composition of the population remains a key predictor of overall fertility in late transitional countries and that low levels of schooling can be a cause of stalling fertility.

Birth Rate↗

Regeneration of Fertile Barley Plants from Mechanically Isolated Protoplasts of the Fertilized Egg Cell.

A simple procedure is described for the mechanical isolation of protoplasts of unfertilized and fertilized barley egg cells from dissected ovules. Viable protoplasts were isolated from ~75% of the dissected ovules. Unfertilized protoplasts did not divide, whereas almost all fertilized protoplasts developed into microcalli. These degenerated when grown in medium only. When cocultivated with barley microspores undergoing microspore embryogenesis, the protoplasts of the fertilized egg cells developed into embryo-like structures that gave rise to fully fertile plants. On average, 75% of cocultivated protoplasts of fertilized egg cells developed into embryo-like structures. Fully fertile plants were regenerated from ~50% of the embryo-like structures. The isolation-regeneration techniques may be largely genotype independent, because similar frequencies were obtained in two different barley varieties with very different performance in anther and microspore culture. Protoplasts of unfertilized and fertilized eggs of wheat were isolated by the same procedure, and a fully fertile wheat plant was regenerated by cocultivation with barley microspores.

Journal Article↗

Complete failure of fertilization in couples with mechanical infertility: implications for subsequent in vitro fertilization cycles.

OBJECTIVE: To determine whether complete failure of fertilization of oocytes in couples with mechanical infertility during the first IVF cycle indicates a poor prognosis for subsequent IVF cycles. DESIGN: A retrospective study of 172 cycles of IVF in 50 couples with mechanical infertility and complete failure of fertilization during their first IVF trial. SETTING: In vitro fertilization unit of the Sheba Medical Center. PATIENTS: Fifty couples undergoing one to eight cycles of IVF for mechanical infertility. MAIN OUTCOME MEASURE(S): Fertilization rate of retrieved oocytes and pregnancy rate. RESULTS: Of the initial 50 couples, 44 underwent additional IVF cycles, and 43 (97.7%) achieved fertilization during the second or third cycle. Twenty-four patients conceived during the study period as a result of IVF. CONCLUSIONS: Complete failure of fertilization in couples with mechanical infertility does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. Complete failure of fertilization during the first cycle of IVF in couples with mechanical infertility is accompanied by a good prognosis for subsequent cycles.

Female↗

Late fertilization of unfertilized human oocytes in in vitro fertilization and intracytoplasmic sperm injection cycles: conventional insemination versus ICSI.

PURPOSE: The aim of this study was to evaluate the efficacy of intracytoplasmic sperm injection (ICSI) in comparison with conventional reinsemination using fertilization failed oocytes by conventional in vitro fertilization (IVF). METHODS: Oocytes were collected from patients of IVF or ICSI cycles. Patients were grouped by fertilization techniques: group 1: conventional IVF; group 2: reinsemination after conventional IVF failure; group 3: regular ICSI; group 4: 1-day-old ICSI after conventional IVF failure; group 5: 2-day-old ICSI after conventional IVF failure; group 6: re-ICSI after regular ICSI failure. RESULTS: In different insemination groups, normal fertilization rate was higher (P < 0.001) in 1-day-old ICSI (47.1%) and 2-day-old ICSI groups (40.0%) than in reinsemination (14.7%). Abnormal fertilization rate was higher (P < 0.05) in re-ICSI group (21.7%) than any other groups (range: 0-8%). Cleavage rate was higher in 1-day-old (36.7%) and 2-day-old ICSI groups (36.0%) than in reinsemination (5.3%, P < 0.001) or re-ICSI groups (17.4%, P < 0.05). Pregnancy rate was 27.6% and 20.0% in conventional IVF and regular ICSI groups, respectively. However, 1-day-old ICSI (group 4) and 2-day-old ICSI (group 5) were attempted once embryo transfer (ET) but failed pregnancy occurred in each group. CONCLUSIONS: In fertilization failure cycles, late ICSI increases the rate of fertilization and embryonic development and may rescue the completely failed attempt of pregnancy.

Adult↗

Evaluation of bull semen fertility by homologous in vitro fertilization tests.

In vitro fertilization assays were performed to investigate their validity in evaluating artificial insemination (AI) bull fertility. A total of 1,532 oocytes, collected from ovaries at the abattoir, were subsequently used in a 4 x 6 x 2 factorial design: 4 doses of heparin added into the capacitation and fertilization medium (0; 0.05; 0.1 and 0.2 micrograms/ml), 6 different bulls with known on-field non-return (NR) rates (range: 64.6-75.3%) and 2 different ejaculates for each bull, collected within a approximately 1-month interval. Oocytes were considered fertilized when 2 pronuclei (or more) were seen in the ooplasm. Both the heparin dose and bull exerted a highly significant effect on the in vitro fertilization (IVF) rates which ranged, per oocyte group, from 30-80%; bull x dose of heparin interaction was significant (P less than 0.001). The 0.05 micrograms/ml dose of heparin was optimal for discriminating individual bulls. At that dose, the correlation coefficients between the bulls, NR rates and the IVF rates from each ejaculate (within-bull or the mean of two ejaculates), were highly significant (r = 0.83). The rates of polyspermy were also significantly influenced by bull and heparin dose, but there was no interaction. In conclusion, capacitation and fertilization in a modified Tyrode medium containing 0.05 micrograms/ml of heparin may be a valuable tool for evaluating AI bull fertility.

Animals↗

A bridge to intracytoplasmic sperm injection--high insemination concentrations benefit patients who have a reduced chance of fertilization with standard in-vitro fertilization.

This study was carried out to determine whether high insemination concentrations (HIC) could improve fertilization and pregnancy rates in patients who had either previously demonstrated poor fertilization rates in vitro using standard protocols (Group 1) or in whom a reduced chance of fertilization was indicated at semen assessment prior to in-vitro fertilization (IVF) (Groups 2 and 3). Forty nine patients were recruited for the study. Standard IVF was carried out in 1 ml volumes using 10(5) spermatozoa/ml. HIC treatment involved co-culture of spermatozoa and oocytes in microdroplets with insemination concentrations increased 10-50 fold higher than standard IVF. Fertilization and pregnancy rates were compared between standard IVF and HIC in individual patients either in consecutive cycles (Group 1) or using sibling oocytes in the same cycle (Group 2). Group 3 patients were treated with HIC for their first treatment cycle. HIC significantly improved the fertilization rate compared with standard IVF for Groups 1 (59.7 +/- 10.7 versus 19.6 +/- 5.4% respectively) and 2 (54.9 +/- 8.5 versus 34.0 +/- 8.5% respectively). HIC increased the pregnancy rate from 0% with standard IVF to 20% per embryo transfer in Group 1 patients. A single pregnancy derived from the transfer of HIC and IVF embryos occurred in Group 2. The fertilization rate (47.2 +/- 7.6%) and pregnancy rate (31.3% per embryo transfer) for Group 3 patients was higher than predicted. There was no increase in the rate of polyploidy with HIC. Provided there are sufficient numbers of motile spermatozoa, HIC may be offered as an initial form of treatment, thus permitting referral of only the poorest responders for intracytoplasmic sperm injection (ICSI).

Adult↗