Prospective, randomized trial of metformin and vitamins for the reduction of plasma homocysteine in insulin-resistant polycystic ovary syndrome

One hundred and two women with insulin-resistant polycystic ovary syndrome were randomized to treatment with a vitamin B preparation, metformin, or both, in conjunction with standard infertility treatment. Plasma homocysteine levels were significantly reduced by both B vitamins and metformin, but to a greater degree by B vitamins, and higher pregnancy rates were associated with vitamin B treatment.     

The effect of two distinct levels of oxygen concentration on embryo development in a sibling oocyte study

Purpose

This prospective randomized study used sibling oocytes of 258 women with ≥8 oocytes to compare the effect of 5 % O₂ versus 20 % O₂ concentrations on embryo development and clinical outcome.

Methods

Oocytes of each case were divided between incubators with either 5 % or 20 % O₂ concentration. Outcome measures were fertilization, cleavage, embryo quality, blastocyst formation, and implantation, pregnancy and live birth rates.

Results

Fertilization and cleavage rates were similar in both groups. The 5 % O₂ group had significantly more blastomeres (P < 0.05) and more top-quality embryos on day 3 (P < 0.02), as well as significantly more available embryos for transfer (31.6 % vs. 23.1 % for the 20 % O₂ group; P < 0.0001). There were significantly more cycles with good embryos in the 5 % group (76/258) than in the 20 % group (38/258) (P < 0.0001). Implantation and pregnancy rates were significantly higher for 5 % O₂ embryos (P < 0.03 and P < 0.05, respectively). Live birth rates per embryo transfer were 34.2 % and 15.8 %, respectively, P < 0.05.

Conclusions

Implantation, pregnancy and live birth rates are higher, and more good quality embryos are available for transfer and freezing with reduced rather than with atmospheric oxygen concentrations during embryo incubation.     

Computerized cell-scanning system for evaluating human spermatogenesis in non-obstructive azoospermic patients

There may be incompatibility between testicular histopathological evaluation and testicular sperm extraction (TESE) outcome. Assessment for sperm presence and different pathological disturbances of non-obstructive azoospermia (NOA) remains challenging. An assay for maximal sampling and accurate identification of testicular cells from NOA patients undergoing TESE and autopsied fertile controls was developed. Testicular cells stained and scanned automatically for morphology underwent fluorescence in-situ hybridization using centromeric probes for chromosomes X, Y and 18 after destaining. Cells were automatically classified according to ploidy, and ratios of haploid cells and autosomal (18) and sex-chromosome bivalent rates were calculated. Identification of testicular cells in suspension enabled prediction of spermatogenesis in seven of eight Sertoli-cell-only syndrome patients. Haploid/diploid cell ratios were 67.6:32.2 for controls and 9.6:90.4 for patients. Both autosomal (18) and sex-chromosome bivalents were present in patients (4.1 ± 5.82%) and controls (19.7 ± 8.95%). Few tetraploid pachytene spermatocytes were observed. More secondary spermatocytes with NOA showed two distinct signals for chromosome 18 (27.9 ± 32.69%) compared with controls (0.4 ± 0.35%). The computerized cell-scanning system enables simultaneous application of morphology and chromosome analysis of testicular cells, which enhance assessing different pathological disturbances and estimating the likelihood of a successful second TESE procedure.     

Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization

OBJECTIVE: To find the type and frequency of chromosomal abnormalities in a selected group of high-order implantation failure (> or =6 IVF trials and > or =15 transferred embryos) and to evaluate its impact on pregnancy outcome.DESIGN: A retrospective study.SETTING: In vitro fertilization (IVF) unit in a university affiliated hospital.PATIENT(S): Sixty-five couples with high-order implantation failure in IVF and embryo transfer.INTERVENTION(S): In vitro fertilization/embryo transfer (ET), work-up for implantation failure, cytogenetic analysis of the couple.MAIN OUTCOME MEASURE(S): We studied the type and frequency of chromosomal changes, quality of embryos, cumulative pregnancy rates, and pregnancy outcome.RESULT(S): The mean number of treatment cycles per patient, before karyotyping was 7.8 +/- 2.4 (range: 6 to 16 cycles). The mean cumulative number of all transferred embryos per patient was 25.7 +/- 10.3 (range: 9 to 65 embryos). Chromosomal abnormalities were found in 10 of 65 (15.4%) cases: translocations in six, mosaicism in two, and inversion or deletion in another two. The morphologic characteristics of the transferred embryos and the cumulative pregnancy rates were similar in patients with implantation failure with and without chromosomal changes. Three of the 16 patients with abnormal karyotype delivered and three miscarried within a follow-up period of 1 year.CONCLUSION(S): A high frequency of chromosomal aberrations was found in a selected group of high-order implantation failures, a similar frequency to recurrent miscarriages. Karyotyping is recommended as part of the work-up for repeated implantation failure in assisted reproduction. Treatment options include further IVF trials, preimplantation genetic diagnosis, or oocyte donation, tailored according to the type of chromosomal change. An international registry should be considered to assist in counseling these patients.     

Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone.

OBJECTIVE: To compare the in vitro fertilization and embryo transfer (IVF-ET) outcome of a 3-day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. DESIGN: Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. SETTING: The IVF-ET program. MAIN OUTCOME MEASURES: Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. RESULTS: The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. CONCLUSION: The ultrashort protocol, although being convenient and having some advantages found in the long GnRH-a protocol, is inferior in its outcome compared with the two other protocols.     

Ovarian pregnancy-a 12-year experience of 19 cases in one institution

OBJECTIVES: To report the prevalence, presentation, diagnostic modalities, and treatment of ovarian pregnancy in one institution. STUDY DESIGN: Retrospective case control study of 19 cases of ovarian pregnancy treated between 1990 and 2001 at Assaf Harofeh Medical Center, Zerifin, Israel. MAIN OUTCOME MEASURES: Prevalence, presentation, diagnostic modalities, surgical treatment, and relation to intrauterine device (IUD) use. RESULTS: Nineteen ovarian pregnancies, diagnosed between 1990 and 2001, comprised (19/694) 2.7% of all ectopic pregnancies, 1:3000 of all live births leading to a mean ovarian pregnancy per year of 1.6. Presenting symptoms were similar to those of tubal pregnancies including circulatory collapse which was present in 4/19 (21%) of patients. Culdocentesis for diagnostic purposes, has become an unnecessary procedure. Wedge resection by laparotomy was the treatment of choice in the past, and from 1994, it was performed exclusively by laparoscopy. When an ovarian pregnancy was diagnosed, intrauterine device was present in 68% of the patients and in 76% of the fertile women. CONCLUSIONS: The absolute number of ovarian pregnancies between 1900 and 2001 increased but the prevalence rate per delivery was stable. Despite modern diagnostic modalities patients still present in circulatory collapse-conservative approach may underestimate the potential risk of bleeding. Culdocentesis has no clinical diagnostic benefits. Laparoscopy is invaluable, as diagnosis and treatment can be carried out as a single treatment. Laparoscopic wedge resection is the treatment of choice. The relation between IUD use and ovarian pregnancies is still strong.     

Outcome of assisted reproductive technology in women over the age of 41

OBJECTIVE: To analyze the results of ongoing pregnancies and deliveries after assisted reproductive technology (ART) in women aged >/=41 years, stratified by year of age. DESIGN: Retrospective study. SETTING: University hospital, IVF unit. PATIENT(S): A total of 431 IVF and intracytoplasmic sperm injection (ICSI) cycles were initiated in women >/=41 years of age. INTERVENTION(S): Medical files of ART patients and pregnancy outcomes were reviewed. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed, and clinical pregnancy and delivery rates. RESULT(S): Of the 431 started cycles, 376 (87%) reached the oocyte retrieval stage. The mean number of oocytes aspirated per patient was 5.4 +/- 0.9 and 6.7 +/- 1.2 in the IVF and ICSI cycles, respectively, and the number of embryos obtained was 2.3 +/- 1.3 and 2.8 +/- 1.6 in the IVF and ICSI cycles, respectively. The number of transferable embryos was 2.0 +/- 1.2 and 2.5 +/- 0.8. The pregnancy rate per oocyte pickup (OPU) was 12.4%; however, the delivery rate per OPU was 4.5%. The mean delivery rate per OPU among women aged 41-43 years was 2%-7%. There were no deliveries aged >/=44 years and no pregnancies at the age of 45 years. The pregnancy and delivery rates of the ICSI and IVF patients were similar after stratification by age. CONCLUSION(S): In our studies, ART performed with homologous oocytes, whether by IVF or ICSI, yielded no clinical pregnancies among women aged >/=45 years and no deliveries aged >/=44 years. The mean delivery rate per oocyte retrieval among women aged 41-43 years varied between 2% and 7%.     

Successful pregnancy after 24 consecutive fetal losses: lessons learned from surrogacy

OBJECTIVE: To offer surrogacy as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 36-year-old woman with 24 consecutive abortions over 11 years. INTERVENTION(S): A regular IVF procedure in the aborting woman and transfer of two good-quality embryos to the surrogate mother, who had previously received hormones. MAIN OUTCOME MEASURE(S): Ovarian response, oocytes, fertilization, and embryo quality in the aborting patient. Endometrial thickness, implantation, pregnancy, and delivery in the surrogate mother. RESULT(S): Transfer of two embryos to the surrogate mother led to a clinical pregnancy, which was uneventful until term. Cesarean section was performed for breech presentation, with delivery of a healthy male. CONCLUSION(S): Surrogacy can be offered as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions.     

Results of in vitro fertilization and embryo transfer by combined long-acting gonadotropin-releasing hormone analog D-Trp-6-luteinizing hormone-releasing hormone and gonadotropins

To avoid cancellation of in vitro fertilization (IVF) because of early luteinization, pituitary suppression by gonadotropin-releasing hormone (GnRH) was carried out in 111 cycles. D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) microcapsules were administered intramuscularly at menstruation and menotropin (hMG) stimulation was started 19 days (mean) later. In 3 cycles (2.7%), only early luteinization occurred. The mean number of oocytes per cycle was 6.7, with a fertilization and cleavage rate of 50 and 95%, respectively. A mean of 3.4 embryos were transferred per cycle. The 111 cycles resulted in 34 clinical pregnancies, 41% per cycle with embryo transfer. The early abortion, multiple pregnancy, and ovarian hyperstimulation rates were 24, 18, and 11%, respectively. It is concluded that D-Trp-6-LH-RH/hMG cycles are associated with a very low occurrence of early luteinization, high number of oocytes and embryos, and a substantial incidence of ovarian hyperstimulation syndrome.     

The comparison of early follicular and midluteal administration of long-acting gonadotropin-releasing hormone agonist

Long-acting GnRH-a (D-Trp6 microcapsules, 3.2 mg) was intramuscularly injected, either in early follicular phase (group A) or midluteal phase (group B). Two hundred sixteen cycles were randomly allocated. Ovarian suppression was significantly more prompt in group B. Follicle cysts were diagnosed in 19% and 16% of groups A and B, respectively; their appearance and regression were significantly more rapid in group B cycles. More ampules of human menopausal gonadotropin were needed in group B. The number of oocytes retrieved was not significantly different between the groups. However, in group A more mature oocytes and more embryos with good morphology were achieved in the patients. Cancellation rate was 2.8% in groups A and B. Pregnancy rate and outcome were similar in both groups.