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Growth hormone for in vitro fertilization.

BACKGROUND: Ovulation induction protocols for in vitro fertilization (IVF) are constantly under review and revision in an attempt to decrease gonadotropin requirements while improving follicular recruitment and pregnancy rate. Most studies of the effect of Growth Hormone on ovulation induction have investigated normally ovulating infertile women. Attention has begun to turn to its effect on women who fail to produce an optimal number of follicles in response to ovulation induction. OBJECTIVES: To assess the effectiveness of growth hormone adjuvant therapy for women undergoing ovulation induction prior to IVF in two patient groups: a) those with no previous history of poor response and b) those with a history of poor response. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Subfertility Group as a whole. Relevant trials were identified in the Group's Specialised Register of Controlled Trials. See Review Group details for more information. SELECTION CRITERIA: All RCTs were included if they addressed the research question posed and provided outcome data for intervention and control subjects. Outcomes of interest included pregnancy, oocyte/embryo number and peak estradiol level. DATA COLLECTION AND ANALYSIS DATA EXTRACTION: A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention. DATA SYNTHESIS: 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. MAIN RESULTS: In women with no previous history of poor stimulation, the common odds ratio for pregnancy per cycle was 0.97 (95% CI 0.34-2. 76) Total dose of gonadotropin and number of oocytes retrieved were similar between treated and placebo groups. In previous poor responders, the common odds ratio for pregnancy per cycle instituted was 2.55 (95% CI 0.64-10.12). Again, no statistically significant difference was noted in gonadotropin dosage or oocyte number obtained, when all studies were considered. REVIEWER'S CONCLUSIONS: Data from 6 small trials suggest that in women with no previous poor response, GH augmentation does not improve the rate of pregnancy. In poor responders, a trend towards improved outcome with GH treatment deserves further study.

Female↗

Pregnancy and birth rates of live infants after in vitro fertilization in women with an without previous in vitro fertilization pregnancies: a study of eight thousand cycles at one center.

OBJECTIVE: Our aim was to compare the cumulative conception and live-birth rates after in vitro fertilization in women undergoing their first course of in vitro fertilization treatment with those in women undergoing their second course of treatment, having previously achieved an in vitro fertilization pregnancy. This study occurred in a tertiary referral-assisted conception unit. STUDY DESIGN: The cumulative conception rates obtained by life-table analysis in 4115 women having their first course of in vitro fertilization therapy (7327 treatment cycles leading to 1123 pregnancies) were compared by means of the log-rank test with those of 331 women in their second course of treatment, having previously achieved an in vitro fertilization pregnancy (561 treatment cycles leading to 138 second in vitro fertilization pregnancies). Similarly, the cumulative live birth rates of 3824 women in their first course of treatment (7136 treatment cycles leading to 732 live births) were compared with those of 105 women in their second course of treatment, having previously achieved an in vitro fertilization live birth (205 treatment cycles leading to 33 second in vitro fertilization live births). RESULTS: The cumulative conception rates and cumulative live birth rates were significantly higher in women having their second course of in vitro fertilization treatment than in those having their first course (cumulative conception rate: p = 0.0001; cumulative live birth rate, p = 0.007). After five cycles of in vitro fertilization, the cumulative conception rates and cumulative live birth rates were 49.8% (95% confidence interval, 46.3% to 53.5%) and 39.0% (95% confidence interval, 35.4% to 42.9%), respectively, in those having their first course of treatment compared with 69.9% (95% confidence interval, 57.6% to 81.3%) and 68.6% (95% confidence interval, 46.1% to 88.5%), respectively, in those having their second course. The estimated median numbers of cycles taken to achieve a pregnancy and live birth (assuming all women could potentially undergo the same number of cycles) were six and eight, respectively, in the first course of treatment compared with only three and five in the second course. CONCLUSION: Women who have achieved a previous in vitro fertilization pregnancy have significantly higher cumulative conception rate and cumulative live birth rates compared with those of women having their first course of treatment.

Adult↗

Outcomes of pregnancies achieved by donor egg in vitro fertilization--a comparison with standard in vitro fertilization pregnancies.

OBJECTIVE: Prior studies on donor egg in vitro fertilization (DE-IVF) outcomes have been limited by the lack of an appropriate control group. Here, we review the obstetric and perinatal outcomes of pregnancies achieved by DE-IVF and compare these pregnancies with those of women who also needed similar assisted reproductive techniques, of similar socioeconomic status, and cared for by a small group of 8 physicians applying consistent diagnostic and treatment approaches. STUDY DESIGN: A retrospective review of 50 consecutive pregnancies achieved by DE- IVF and 50 consecutive pregnancies achieved by standard IVF (STD-IVF) was performed. Comparisons were made for demographic and medical confounding factors and for outcome measures. RESULTS: The 2 groups were nearly identical for gravidity, parity, and multiple gestations but did vary in maternal age. Average age of patients receiving DE-IVF was 41.9(+/-5.1), whereas the STD-IVF averaged 37.7(+/-3.6) years ( P < .001). Key obstetric outcomes did not differ between the 2 groups with the exception of pregnancy-induced hypertension. In patients with DE-IVF, 26% had pregnancy-induced hypertension (PIH) develop, whereas this occurred in only 8% of the STD-IVF group ( P = .02). Examining nulliparous patients only, 37.1% of DE-IVF had PIH develop, whereas only 8% of STD-IVF group achieved that diagnosis ( P < .003). An analysis with a multiple logistic regression in nulliparous patients found odds ratios of 7.1 (95% CI, 1.4-36.7) in DE versus STD-IVF, odds ratio 4.9 (95% CI, 1.3-18.3) for multiple gestation versus singleton, and odds ratio 1.0 (95% CI, 0.9-1.1) for maternal age. CONCLUSION: Nulliparous pregnancies achieved by DE-IVF are associated with an increased risk of PIH; however, excellent outcomes can still be expected.

Adult↗

Delayed fertilization during in vitro fertilization and embryo transfer cycles: analysis of causes and impact on overall results.

This study evaluated possible causes of delayed fertilization during in vitro fertilization (IVF) cycles, its repetitiveness, and its influence on IVF results in 23 patients (27 cycles) with delayed fertilization of greater than or equal to 1 preovulatory oocyte(s). In 15 cycles, reinsemination with husband's semen was performed at 18 hours. Possible causes of delayed fertilization were oocyte defects (10 cycles, 37.0%), sperm defects (4 cycles, 14.8%), oocyte and sperm defects (4 cycles, 14.8%), and no detectable gamete defects (9 cycles, 33.3%). Overall fertilization rate was 47.9%. No pregnancies were observed in 10 patients with one embryo transferred. Recurrence rate of delayed fertilization per patient was 17.3%; overall ongoing pregnancy rate/cycle was 10.3%. Although repetitiveness of delayed fertilization is low, it seems to impact negatively on IVF results.

Embryo Transfer↗

In vitro fertilization of in vitro matured canine oocytes using frozen-thawed dog semen.

Experiments were conducted to evaluate in vitro fertilization (IVF) of in vitro matured (IVM) bitch oocytes using dog spermatozoa frozen in three different extenders. Sperm-rich fraction from eight ejaculates of five dogs was frozen in each one of three egg yolk Tris extenders with additional: (A) 1.4 g citric acid and 0.8 g glucose; (B) 0.7 g citric acid and 3.5 g glucose; or (C) 1.4 g citric acid and 0.8 g fructose (all with 5% glycerol in 100 mL milliQ water). Thawed sperm were co-incubated with IVM bitch oocytes for 6 h. Oocytes were fixed and evaluated under an epifluorescence microscope; penetrated oocytes were defined as those having sperm heads in the perivitelline space or in the oocyte cytoplasm. Higher penetration rates (P < 0.05) were obtained in oocytes cultured with spermatozoa frozen in extenders B and C than those frozen in extender A (33.1, 34.2 and 26.4%, respectively).

Animals↗

Effects of oxygen tension in the gas atmosphere during in vitro maturation, in vitro fertilization and in vitro culture on the efficiency of in vitro production of mouse embryos.

Effects of oxygen (O2) tension in the gas atmosphere during in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) on the efficiency of in vitro production of mouse embryos were examined. Mouse oocytes recovered from large antral follicles were subjected to IVM in Waymouth medium for 15, 16 and 17 hr under 5 or 20% O2 and then subjected to IVF and IVC under 5 or 20% O2 tension. Lowering the O2 tension in the gas atmosphere for IVM from 20 to 5% improved the cleavage rate after IVF when the oocytes were subjected to IVM for 15 hr; however, no improvement in the cleavage rate was observed when the culture period for IVM was extended to 16 and 17 hr. Lowering the O2 tension to 5% for IVM and IVC improved the development of the cleaved oocytes to the blastocyst stage, regardless of the culture period for IVM. However, the O2 tension for IVF had no remarkable effect on the subsequent embryonic development. These results demonstrate that 5% O2 is superior to 20% O2 for IVM and IVC, and suggest that 20% O2 for IVM may delay oocyte maturation and/or the acquisition of fertilizability and impair the developmental competence of oocytes.

Animals↗

Birth of piglets preselected for gender following in vitro fertilization of in vitro matured pig oocytes by X and Y chromosome bearing spermatozoa sorted by high speed flow cytometry.

The present study examined the ability to establish pregnancies after transfer of pig embryos derived from in vitro fertilization (IVF) of in vitro matured (IVM) oocytes by X and Y chromosome-bearing spermatozoa sorted by flow cytometry. Cumulus-oocyte complexes (COC) were cultured in BSA-free NCSU-23 medium containing porcine follicular fluid (10%), cysteine (0.1 mg/mL), epidermal growth factor (10 ng/mL), LH (0.5 microgram/mL) and FSH (0.5 microgram/mL) for 22 h, then the oocytes were cultured without hormonal supplements for an additional 22 h. Boar semen was collected and prepared by flow cytometry sorting of X and Y chromosome bearing spermatozoa. After IVM, cumulus-free oocytes were co-incubated with sorted X or Y spermatozoa (2 x 10(4)/mL) for 6 to 7 h in modified Tris-buffered medium containing 2.5 mM caffeine and 0.4% BSA. After IVF, putative embryos were transferred to NCSU-23 medium containing 0.4% BSA for culture. A portion of the oocytes was fixed 12 h after IVF, the remainder were cultured up to 96 h. At 96 h after IVF, 8-cell to morula stage embryos (n = 30 to 35) from each gender were surgically transferred to the uterus of recipient gilts. Insemination of IVM pig oocytes with X- or Y-bearing sperm cells did not influence the rate of penetration (67 vs 80%), polyspermy (40 vs 53%), male pronuclear formation (95 vs 96%), or mean number of spermatozoa per oocyte (1.6 vs 1.6), respectively. Furthermore, no difference was observed between cleavage rates at 48 h after IVF (X, 49 vs Y, 45%). Transfer of embryos derived from X-bearing spermatozoa to 18 recipients resulted in 5 pregnancies and delivery of 23 females and 1 male piglet. Similarly, transfer of embryos derived from Y-bearing sperm cells to 10 recipients resulted in 3 pregnancies, with 9 male piglets delivered. The results show that X- and Y-bearing spermatozoa sorted using USDA sperm sexing technology can be successfully used in an IVM-IVF system to obtain piglets of a predetermined sex.

Animals↗

Failure of fertilization in in vitro fertilization: the "occult" male factor.

Failure of fertilization in patients undergoing in vitro fertilization (IVF) deserves extensive analysis for better prediction of the success or failure of this therapeutic modality. Consequently, we retrospectively studied the 52 couples in whom fertilization failed during Norfolk series 18 to 25, in an effort to establish the precise causes of failure. In the initial evaluation, pure oocyte abnormalities were identified in 19.2% of the cases; 32.6% showed sperm abnormalities, and a combination of oocyte and sperm anomalies was found in 7.7%. In 40.4% of the cases, failure of fertilization could not be explained. Reassessment of sperm morphology by new, strict criteria increased the identification of sperm abnormalities to 61.5% and of combined sperm and oocyte anomalies to 13.4%, for a total of 74.9% of sperm factors involved, as opposed to 40.3% in the original evaluation. The incidence of unexplained failed fertilization was substantially reduced, to 11.5%. In a control group (tubal infertility) matched by age, date, and stimulation, in whom fertilization occurred, 83.3% had normal sperm parameters as judged by the new criteria for morphology evaluation. This paper emphasizes the need for a more accurate diagnosis of sperm abnormalities to establish the true incidence of this factor in failed fertilization and to obtain information of prognostic value to patients and clinicians.

Adult↗

Chromosome abnormalities in human embryos after in vitro fertilization.

In vitro fertilization and embryo transfer is now an established treatment for certain forms of human infertility. High success rates have been reported following oocyte recovery and fertilization in vitro, the only major remaining difficulty being the high failure rate (80%) of implantation after replacement of the embryo into the mother. One possible reason for this failure of implantation is that some embryos may carry a lethal chromosome abnormality which does not allow development beyond the preimplantation stage. The need for information on the chromosomal status of early embryos fertilized and developed in vitro is recognized but two reported attempts to examine them have met with technical problems. Here we describe a method for examining chromosomes in 8-cell human embryos. Although we have made complete chromosome analyses for only three oocytes, our findings are surprising in that two of the three embryos were chromosomally abnormal. Data on the DNA content of the nuclei in a further eight cases showed that approximately 20% overall may be haploid.

Age Factors↗

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↗

Male-factor infertility and in vitro fertilization.

In vitro fertilization (IVF) was developed primarily as a treatment for female and idiopathic infertility. However, with the discovery that relatively few sperm are required to achieve fertilization in vitro, it was proposed that IVF could be used also as an effective treatment for male-factor infertility. This review deals with the work that has been carried out by various groups in this area of male-factor infertility. As the standards of classification and the presentation of results vary from group to group, this also shows that there is a need for some standardization of how patient selection and the presentation of results are carried out in the area of male-factor infertility.

Cell Separation↗

The first dromedary (Camelus dromedarius) offspring obtained from in vitro matured, in vitro fertilized and in vitro cultured abattoir-derived oocytes.

Dromedary offspring have never been produced fully in vitro. We have previously demonstrated that embryos obtained by culture in semi-defined medium (mKSOMaa) have better in vitro development ability than those cultured with oviductal epithelial cells. The aim of the present experiment was to study the pregnancy rate after embryo transfer of in vitro-produced (IVP) dromedary embryos cultured in semi-defined modified medium (mKSOMaa). IVM/IVF procedures were conducted on six hundred and sixty four (664) cumulus oocytes complexes (COCs) aspirated from ovaries collected at a local slaughterhouse and cultured in vitro (38.5 degrees C; 5% CO2, and maximum humidity >95%). Maturation was completed by incubation in TCM-199 medium supplemented with 10% heat-treated Fetal Calf Serum (FCS), 10 ng/mL EGF, 1 microg/mL FSH, 1 microg/mL E2 and 500 microM cysteamine for 30 h. In vitro fertilization was performed using fresh semen (0.5 x 10(6) spermatozoa/mL in modified TALP-solution). Fertilized oocytes were cultured in mKSOMaa, under 38.5 degrees C, 5% CO2 and 90% N2 with maximum humidity (>95%). All IVC steps were done in seven replicates. The cleavage rate (two cells to blastocyst stage) was 64% (425/664) and the percentage of oocytes reaching the blastocyst stage was 23% (155/664). The hatching rate of blastocyst obtained after culture was 46% (71/155). Good quality hatched blastocysts (n = 66) were transferred individually to synchronized recipients. Pregnancy rates, determined by ultrasonography at 15, 60 and 90 days after embryo transfer (ET), were 38%, 32% and 27%, respectively. Out of 18 pregnant females 5 aborted between the fifth and seventh month of pregnancy and 13 females (20%) remained pregnant. After 385 days of pregnancy, the first healthy and normal male-dromedary offspring produced fully in vitro was born at a birth weight of 38 kg. More dromedary calves (n = 4) were born later on. The remaining pregnant females (n = 8) are due to calf within the next months. In conclusion, this is the first reported offspring in camelids obtained by transfer of embryos produced by IVM, IVF and IVC using abattoir-derived oocytes, fresh semen and culture in a semi-defined medium.

Animals↗

[Age and in vitro fertilization. French National Register on In Vitro Fertilization].

The mean age of IVF patients women and men is always increasing, this is probably due to the late desire for pregnancy nowadays. Pregnancy rate decreases with the age of wife and in a minor way with the age of man. The most important factor is the quality of woman answer to ovarian stimulation. Among women of 42 or over, the one with a high estradiol level on hCG day (> 4000 pg/ml) are the only older women with a correct pregnancy rate.

Adult↗

In-vitro fertilization pregnancies in Australia and New Zealand, 1979-1985. Australian In-Vitro Fertilization Collaborative Group.

We report here data on 1510 pregnancies that resulted from in-vitro fertilization in 12 in-vitro fertilization units in Australia and in one unit in New Zealand in the period 1979 to 1985. Live births occurred in 57.5% of all pregnancies (including preclinical abortions) and in 69.0% of clinical pregnancies. There was a high incidence of ectopic pregnancies (5.2% of clinical pregnancies) and spontaneous abortions (24.3% of intrauterine pregnancies). Of 902 viable pregnancies, 202 (22.4%) pregnancies resulted in multiple births. There were 700 infants who were born after singleton births and 438 infants who were born after multiple births. The over-all incidence of preterm delivery was 27.0%, with an incidence of 18.5% of singleton pregnancies. Low birth weight occurred in 34.8% of infants. The perinatal death rate was 47.5 deaths per 1000 births; still births accounted for three-quarters of these deaths. These findings can be used to counsel infertile couples about the risks of reproductive losses after treatment by in-vitro fertilization. National health surveys should include questions that relate to the prevalence of infertility to encourage studies of the prevention of infertility and to assess the requirements for clinical services.

Adult↗