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Differences in in vitro fertilization (IVF) outcome between white and black women in an inner-city, university-based IVF program.

OBJECTIVE: To compare IVF outcomes between white and black women in an inner-city, university-based IVF program. DESIGN: Retrospective study. SETTING: University-based IVF program. PATIENT(S): Ninety-five white women undergoing 121 cycles and 37 black women undergoing 47 cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate and pregnancy rate (PR). RESULT(S): Black women constituted 28. 0% of the population and underwent 28.0% of the total cycles. There were no statistically significant differences in age, basal FSH, number of ampules, duration of stimulation, endometrial thickness, P on the day of hCG, cancellation rate, number of oocytes, or embryos transferred. However, the duration of infertility, body mass index (BMI), incidence of tubal-factor infertility, and peak E(2) levels were significantly higher in black women. In addition, a larger proportion of black women required aggressive stimulation than white women (70.2% and 43.0%). Both implantation rates and clinical PRs were significantly lower in black women than in white women (9.8% and 19.2% compared with 23.4% and 42.2%, respectively). CONCLUSION(S): Black women have poorer IVF outcomes than white women. These differences can be partly explained by higher BMI, longer duration of infertility, higher incidence of tubal-factor infertility, and higher peak E(2).

Academic Medical Centers↗

Chromosome analysis of spontaneous abortions after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

OBJECTIVE: To verify the hypothesis that the incidence of chromosomal abnormalities significantly increases in the products of conception of males with sub-fertility, treated with assisted reproduction techniques (ART). STUDY DESIGN: All removed products of conception tissues were analyzed with standard cytogenetic techniques. A karyotype of the abortions was possible in 35 cases of IVF and 29 of ICSI. RESULTS: 15/35 (43%) IVF abortions and 14/29 (48%) ICSI abortions, respectively, have shown a chromosomal abnormality. The most frequent abnormality was monosomy X (45,X0). CONCLUSION: No significant difference in the incidence of embryonic anomalies was found between IVF and ICSI group. However, both IVF and ICSI allow pre-implantation diagnosis and embryo chromosomal evaluation should be considered, before transfer. Genetic counselling and consideration of prenatal diagnosis is suggested as integral part of planning of treatment strategies for 'at risk couples'.

Abortion, Spontaneous↗

Experience with intravaginal culture for in vitro fertilization (IVF).

It has been reported that intravaginal culture (IVC) yields results comparable to those obtained with classic IVF techniques; furthermore, it can simplify and reduce the costs of the procedure. In our experience with IVC however, only 8 of 78 mature oocytes inseminated (10.2%) fertilized. Possible causes of this low fertilization rate were analyzed. In our opinion this new and attractive technique needs further evaluation before being extended to common clinical practice.

Cells, Cultured↗

Does patient semen quality alter during an in vitro fertilization (IVF) program in a manner that is clinically significant when specific counseling is in operation?

PURPOSE: It has been shown that the stress of infertility may impair semen quality. Whether counseling can attenuate this affect is unproven. This study examines, in an IVF program setting, where specific counseling is in operation, whether semen collected on the day of oocyte recovery is significantly different from that obtained during the prior clinical suitability assessment of the couple. RESULTS: In the 125 consecutive couples examined, there were no significant overall differences in semen volume or sperm density. There was a significant increase in sperm motility on the day of oocyte retrieval (P < 0.001). Twenty-three patients (18.4%) showed an increase in quality, and 21 (16.8%) a decrease, on the day of oocyte recovery. The environment of production appeared to exert no influence. Fertilization failure occurred in seven couples, three (14%) of whom presented for the first time with decreased semen parameters on the day of IVF. This compares with 1 of 23 (4%) fertilization failure in those whose parameters increased. CONCLUSION: The semen quality of the vast majority of the patients studied in this highly counseled program does not appear to be significantly affected by the superstress of participation in the day of oocyte recovery.

Adult↗

Cumulative birth rates following cryopreservation of all embryos in stimulated in vitro fertilization (IVF) cycles.

OBJECTIVE: To cryopreserve all good-quality embryos available after IVF is one way to avoid an impending hyperstimulation and a more attractive alternative to a couple than cancellation of the cycle. At Sahlgrenska University Hospital this method has been practiced since 1991. The aim of this study was to assess the success rate (defined as childbirth per couple) after IVF treatment including one stimulated cycle, resulting in cryopreservation of all good-quality embryos available, followed by replacement of frozen/thawed embryos in one or more natural cycles. DESIGN: A cohort of 32 women undergoing one stimulation for IVF between January 1991 and December 1993 where all good-quality embryos were cryopreserved and transferred in a later spontaneous cycle were studied retrospectively. The cumulative childbirth rate per couple was calculated. RESULTS: A total of 28 women underwent a total of 45 transfers with frozen-thawed embryos. In 4 women no transfer has taken place so far. The clinical pregnancy rate per embryo transfer was 33% (15/45) and per patient 54% (15/28). Three spontaneous abortions occurred giving a cumulative childbirth rate per patient of 39% (11/28). In addition, 6 out of the 28 women still have embryos left in the freezer. CONCLUSION: Cryopreservation of all good-quality embryos available after IVF is a highly effective alternative to cancellation of a cycle when there is impending hyperstimulation. The use of this approach results in a cumulative childbirth rate per couple of at least 39%. Since only one stimulation was performed, it also seems to be cost effective.

Abortion, Spontaneous↗

Use of stimulated serum estradiol measurements for the prediction of hyperresponse to ovarian stimulation in in vitro fertilization (IVF).

PURPOSE: In ovarian stimulation an exaggerated ovarian response is often seen and is related to medical complications, such as ovarian hyperstimulation syndrome (OHSS), and increased patient discomfort. If it were possible to identify hyperresponders at an early stage of the stimulation phase, adaptation of the stimulation protocol would become feasible to minimize potential complications. Therefore, we studied the usefulness of measuring stimulated serum estradiol (E2) levels in predicting ovarian hyperresponse. METHODS: A total of 109 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. The E2 level was evaluated on day 3 and 5 of the stimulation phase. Two outcome measures were defined. The first was ovarian hyperresponse (collection of > or = 15 oocytes at retrieval and/or peak E2 > 10000 pmol/L, or cancellation due to > or = 30 follicles growing and/or peak E2 > 15000 pmol/L, or OHSS developed). The second outcome measure comprised a subgroup representing the more severe hyperresponders. named extreme-response (cancellation or OHSS developed). RESULTS: The data of 108 patients were analyzed. The predictive accuracy of E2 measured on stimulation day 3 towards ovarian hyperresponse was clearly lower than that of E2 measured on stimulation day 5 (area under the receiver operating characteristic curve (ROCAUC) 0.75 and 0.81, respectively). For extreme-response the predictive accuracy of E2 measured on stimulation day 3 or 5 was comparable (ROCAUC 0.81 and 0.82, respectively). For both outcome measures the stimulated E2 tests yielded only acceptable specificity with moderate sensitivity at higher cutoff levels. Prediction of extreme-response seemed slightly more effective due to a lower error rate. CONCLUSIONS: There is a significant predictive association between E2 levels measured on stimulation day 3 and 5 and both ovarian hyperresponse and extreme-response in IVF. However, the clinical value of stimulated E2 levels for the prediction of hyperresponse is low because of the modest sensitivity and the high false positive rate. For the prediction of extreme-response the clinical value of stimulated E2 levels is moderate.

Adult↗

Human amniotic fluid for fertilization and culture of human embryos: results of clinical trials in human in vitro fertilization (IVF) programs.

We report the outcome of clinical trials carried out in two IVF programs, comparing the use of human amniotic fluid (HAF) as a complete medium to Whittingham's T6 medium containing human serum (T6 + 10% HS) for egg incubation, insemination, embryo culture, and embryo transfer. There were no significant differences in the clinical trials between HAF used alone as a complete medium and T6 + 10% HS in fertilization rates of eggs, cleavage rates of embryos up to 48 hours in culture, pregnancy success rates after embryo replacement or the outcome of pregnancies. There was no advantage in using T6 + 10% HS for fertilization of eggs and HAF as a complete medium for embryo culture and transfer in any of the parameters examined. We conclude that HAF does not meet the complete requirements of human eggs and embryos in vitro and further developments of culture media are required to obtain embryo development equivalent to that in vivo.

Amniotic Fluid↗

[Pregnancy after direct oocyte-sperm transfer (DOST)--a simple alternative to in vitro fertilization (IVF)].

We report on the first pregnancies achieved at our clinic following direct oocyte-sperm-transfer (DOST). Immediately after follicular aspiration, oocytes together with spermatozoa prepared by the swim-up-technique are transferred to the uterus in a manner similar to the embryo transfer following IVF. Our study population consists of 9 patients with bilateral tubal occlusion, accompanied by a male factor in three cases. Up to now, we have achieved four pregnancies, including one twin pregnancy, all occurring, when a male factor was absent. The method described appears promising in terms of efficiency, reduction in the costs and technical procedures during treatment of human infertility.

Embryo Transfer↗

Anti-human gonadotropin antibodies generated during in vitro fertilization (IVF)-related cycles: effect on fertility of rhesus macaques.

Administration of human gonadotropins such as hFSH, hLH, and hCG to rhesus macaques can result in formation of anti-human gonadotropin antibodies. To determine whether the presence of these antibodies interferes with subsequent fertility, sixteen female rhesus macaques (Macaca mulatta) with known antibody levels were bred with male rhesus macaques. The presence of antibodies did not interfere with conception or maintenance of pregnancy. Furthermore, antibody titers did not increase during gestation or following the resolution of pregnancy.

Animals↗

Pituitary down-regulation using leuprolide for the intensive ovulation management of poor prognosis patients having in vitro fertilization (IVF)-related treatments.

A review of 118 treatment cycles in 115 women under prolonged GnRH analogue (GnRHa; leuprolide) treatment is presented. Patients were selected for treatment primarily on the grounds of poor previous response to stimulation (n = 40), advanced age (greater than 35 years; n = 29), previous premature luteinizing hormone (LH) surge (n = 30), polycystic ovarian disease (PCO; n = 12), and elevated androgens without evidence of PCO (n = 5). An overall pregnancy rate of 28.8% per treatment cycle was attained, compared with a pregnancy rate of 6.2% (6/97, of which none went to term) in the previous completed treatment cycle for the same patients. Ovarian response, as measured by oocytes recovered and maximum estradiol levels observed, was significantly improved in all groups and this was associated with a prolonged follicular phase, significantly more human menopausal gonadotropin (hMG) stimulation and a relatively high incidence of ovarian hyperstimulation, particularly in pregnant patients. Of specific techniques in the GnRHa cycle, GIFT produced a pregnancy rate per treatment of 50% (10/20); IVF-ET, 22% (8/36); PROST, 28% (13/46); and TEST, 19% (3/16). No cycles were abandoned, compared with a cancellation rate of 24% in previous cycles without GnRHa. Patients with PCO performed particularly well on GnRHa management, with a pregnancy rate per treatment of 58% (7/12). Pregnancy rates per treatment for the other groups were as follows: elevated age, 27% (9/33), high androgens, 40% (2/5); premature LH surges, 32% (9/28); and poor responders, 17.5% (7/40).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Combined treatment with gonadotrophin releasing hormone agonist and gonadotrophins in poor responders to hyperstimulation for in vitro fertilization (IVF): clinical and endocrine results.

Seventy three cycles of combined gonadotrophin releasing hormone (GnRH) agonist/gonadotrophin treatment for IVF controlled ovarian hyperstimulation in previous poor responders to standard ovarian hyperstimulation therapy are reported. Oocyte numbers obtained were better than the previous average results, but were similar to the previous best response. In general more oocytes than the previous mean could be expected but low order responders were not transformed into high order responders. Pregnancies did occur in this difficult group of patients but the rate was modest. Because of a reduction in cancelled cycles, patients might reduce their total costs in time and gonadotrophin used, however this treatment is not a panacea for the true low order responder.

Adult↗

Early first-trimester ultrasound provides a window through which the chorionicity of twins can be diagnosed in an in vitro fertilization (IVF) population.

PURPOSE: Early and accurate diagnosis of placentation alerts the obstetrician to potential clinical sequelae. The reproductive endocrinologist has a unique opportunity to sonographically evaluate the very early intrauterine pregnancy. We undertook this study to determine whether chorionicity could accurately be predicted using early first-trimester transvaginal ultrasound. RESULTS: Of 47 sets of twins conceived through our IVF-ET program, all underwent detailed transvaginal sonography. These findings were then compared with results of placental pathology examination, after birth. Transvaginal sonography was performed 41 days following embryo transfer. All 3 monochorionic placentas were correctly predicted by ultrasound, while the remaining 44 placentas were dichorionic. CONCLUSIONS: The significance of our findings lies both in our 100% accuracy in diagnosis and in the extremely early gestational age at which we were able to establish correctly the diagnosis of chorionicity. The errors in diagnosis made by previous investigators were often the result of not recognizing single placentae which were later histologically shown to be the result of placental fusion. The infertility specialist has a unique window of opportunity to evaluate placentation and should provide useful information regarding chorionicity to the obstetrical team.

Chorion↗

Chromosome 18 analysis by fluorescence in situ hybridization (FISH) in human blastomeres of abnormal embryos after in vitro fertilization (IVF) attempt.

We performed fluorescence in situ hybridization (FISH) with a chromosome 18-specific probe on human abnormal cleaved embryos, fertilized either by two spermatozoa and exhibiting three pronuclei (3 PN) or normally fertilized and exhibiting two pronuclei (2 PN) with subsequent severe fragmentation and/or blocking. The aim of the study was to evaluate the incidence of chromosome 18 anomalies among these embryos in order to evaluate the FISH efficiency on such material and to obtain more precise and complete data than those obtained with classical cytogenetic analysis. For the 3 PN cleaved embryos, FISH confirmed the frequent regulation towards diploidy (25 per cent) and the high frequency of mosaics (53 per cent). For the 2 PN blocked or damaged embryos, FISH permitted chromosome evaluation, which was otherwise impossible with classical cytogenetic techniques: we also found a high mosaic frequency (45 per cent) with these embryos. If this frequency were the same for normally developing embryos, it would be a major obstacle to the reliability of either chromosomal or genetic preimplantation diagnosis.

Blastomeres↗

Experience with GnRH agonists in an in vitro fertilization (IVF) program.

The experience using pre-treatment with GnRH-agonists in an IVF-program are reported. 55 patients having a 'poor response', premature LH surge, or follicular luteinization in previous treatment cycles were treated for a total of 68 cycles. Therapy with GnRH agonists was initiated in the midluteal phase, and given by self-administration subcutaneously. Stimulation started with exogenous gonadotropins on a fixed day (Saturday) after pituitary desensitization had first been obtained, and resulted in all follicular punctures being performed on weekdays. Five treatment cycles (7.4%) were cancelled because of 'poor response'. Where the indication for GnRH-agonist therapy was previous 'poor response', a cancellation rate of 36.4% was observed, whereas a cancellation rate of only 1.8% was found in the other indication groups (p less than 0.001). Altogether 26 clinical pregnancies were achieved, five of these ending in a spontaneous abortion. The rate of deliveries was 33% per oocyte retrieval, and 40% per pre-embryo replacement.

Buserelin↗

Use of coculture with cumulus cells in insemination medium in human in vitro fertilization (IVF).

PURPOSE: In an initial trial, 16 of 33 (48%) bipronuclear human zygotes left in culture in the insemination drop from which they had originated developed to fully expanded blastocysts. RESULTS: This method was subsequently used for all supernumerary embryos judged unsuitable for replacement or cryopreservation on Day 1, 2, or 3 of development. Over a 4-year period, embryos reaching the fully expanded blastocyst stage were cryopreserved. Of 113 such blastocysts thawed, 81 survived (72%), and upon transfer to 52 patients, 8 clinical pregnancies were established (15%), of which 6 were live births. Subsequently, following modification of some culture parameters, 60 patients had 296 supernumerary embryos cultured for 6 days; 43 of these patients (72%) had 148 embryos (50%) that cavitated and 134 (45%) of these cavitating embryos were judged to be fully expanded blastocycts; 125 (42%) of these embryos were cryopreserved. CONCLUSION: The blastocyst formation rate is similar to that reported by others using conventional culture procedures or coculture on Vero or other cell types. I conclude that cumulus cells are a ready source of feeder cells for the coculture of human embryos.

Blastocyst↗

Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development.

OBJECTIVE: To evaluate the effects of vaginally administered sildenafil on endometrial thickness and IVF outcome in a large cohort of infertile women with poor endometrial development. DESIGN: Retrospective cohort analysis. SETTING: Private practice setting. PATIENT(S): A cohort of 105 infertile women aged <40 years, with normal ovarian reserve and at least two consecutive prior IVF failures attributed to inadequate endometrial development. INTERVENTION(S): Patients underwent IVF using a long GnRH-a protocol with the addition of sildenafil vaginal suppositories (25 mg, 4 times per day) for 3-10 days. MAIN OUTCOME MEASURE(S): Peak endometrial development, pregnancy, and implantation rates. RESULT(S): Of 105 patients, 73 (70%; Group A), attained an endometrial thickness of >/=9 mm, whereas 32 (30%; Group B) did not. Implantation and ongoing pregnancy rates were significantly higher for Group A (29% and 45%) than for Group B (2% and 0). Of 11 women in Group B who had embryos transferred in that cycle, only one conception occurred, which resulted in a miscarriage. In Group B, 59% of women had a history of endometritis, compared with 44% in Group A. CONCLUSION(S): Vaginal administration of sildenafil enhanced endometrial development in 70% of patients studied. High implantation and ongoing pregnancy rates were achieved in a cohort with a poor prognosis for success. Previous endometritis may decrease the response to sildenafil.

Administration, Intravaginal↗

Sonographic evaluation of the endometrium in in vitro fertilization IVF cycles. A way to predict pregnancy?

The endometrial thickness and echogenic pattern were prospectively evaluated in 100 patients undergoing IVF-treatment. On the day before oocyte aspiration (day-1) the endometrium was significantly thicker in the group of patients achieving an ongoing pregnancy than in the group that failed to conceive. The minimal endometrial thickness on day-1 compatible with an ongoing pregnancy was 9 mm. Before oocyte aspiration two different endometrial patterns could be distinguished, a multilayered, 'triple line', hypoechogenic endometrium (A) and an isoechogenic pattern (B). Other studies have, in addition, described a hyperechogenic endometrium with a poor pregnancy rate but that pattern could in the present study only be demonstrated after follicle aspiration, 32 clinical pregnancies occurred. Among patients with endometrial pattern A, 36% conceived and among patients with pattern B 23% conceived which was not significantly different. It is concluded that the day before aspiration an endometrial thickness of at least 9 mm appears to be required for an ongoing pregnancy. In all cases a triple line (hypo-or isoechogenic) pattern was evident before aspiration.

Adult↗

Atypical response to luteinizing hormone-releasing hormone (LH-RH) agonist (suprefact nasal) in induction of ovulation in in vitro fertilization (IVF).

Animal and human research has indicated the presence of receptors to luteinizing hormone-releasing hormone (LH-RH) in the ovaries. However, the role of these receptors is not yet clear. Forty-five patients were treated with Suprefact (D-Serg-Des-Gly10-GnRGH), starting in the midluteal phase of a nonstimulatory menstrual cycle. The Suprefact (300 micrograms t.i.d.) was administered as a nasal spray until the administration of human chorionic gonadotropin (hCG). On the third to fifth day of the following menstrual cycle, the patients were treated with a high dose of human menopausal gonadotropin (hMG). hCG was administered when at least two follicles reached a mean diameter of 18 mm. Five of these patients who ovulated spontaneously and had normal menstrual cycles did not respond to the stimulation with hMG. Treatment was stopped after 12 days of hMG administration. During the following cycle of the five patients, levels of gonadotropins were found to be in the normal range, and all of them responded as expected to hMG administered for 3 days only (hMG test). These findings suggest that LH-RH agonist may interfere with ovarian steroidogenesis.

Administration, Intranasal↗