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Objective: To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM., Design: Meta-analysis., Methods: This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously., Results: The overall odds ratio for MM in our original meta-analysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23)., Conclusions: Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

Direct transcervical transfer of spermatozoa and oocytes to the uterine cavity has been carried out in the past. This procedure could be a more appropriate approach than IVF for some anovulatory patients who require gonadotrophin stimulation, since the number of oocytes could be limited, thus reducing the occurrence of multiple gestations. However, most of the clinical pregnancy rates reported in the literature for gamete intrauterine transfer appear to be inferior to IVF pregnancy rates. This study attempted to improve the outcome of gamete intrauterine transfer by modifying some aspects of the procedure. This procedure is referred to as uterine sperm-egg transfer (U-SET) to imply that U (you the patient) set (determine) the number of oocytes to be transferred to the uterus. In this study's series of 16 anovulatory patients under the age of 36 years, the clinical pregnancy rate was 69% and the live birth rate was 50%., (2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Blastocyst culture has reduced the number of embryos transferred per cycle, whilst simultaneously creating new quandaries regarding supernumerary blastocyst cryopreservation. This retrospective study was undertaken to compare a slow freezing protocol to a vitrification protocol for cryopreservation of day 5 and day 6 human blastocysts. To demonstrate this, the survival, implantation rate and pregnancy rates were compared after thawing, assessment and embryo transfer of 86 consecutive day 5 and day 6 thawed blastocyst transfer cycles from January 1, 2002 to December 31, 2003. Seventy-one day 5 slow-frozen (SF) blastocysts were thawed and 59 embryos survived the thawing (83.1%). An average of 2.5 SF blastocysts was replaced per embryo transfer, resulting in a pregnancy rate of 16.7% (4/24). Concurrently, 41 vitrified (VIT) blastocysts were thawed and all 41 survived the thawing process (100%). An average of 2.0 VIT blastocysts was replaced per embryo transfer, resulting in a pregnancy rate of 50% (10/20). Survival, pregnancy and implantation rates of day 5 VIT blastocysts have significantly increased (P < 0.01, P < 0.02 and P < 0.01 respectively) over day 5 SF blastocysts. A similar trend was observed with day 6 blastocysts.

Purpose: To estimate the risk of major malformations in IVF and ICSI infants., Methods: Forty-four studies published in English since 1990 where the major malformation rate for IVF or ICSI cases was compared to an appropriate control group were reviewed. Nineteen studies met all selection criteria. In addition, a quality score was developed to assess each study based on sample size, timing of diagnosis, appropriateness of control group and other factors., Results: In 19 studies, the major malformation rates ranged from 0-9.5% for IVF; 1.1-9.7 for ICSI; and 0-6.9% in the control groups. When ICSI was compared to IVF, and multiple births compared to singleton, there were no statistically significant differences. When data from 16 studies involving 28,524 IVF infants and 2,520,988 spontaneously conceived controls and 7 studies involving 7234 ICSI infants and 978,078 controls were pooled, we found an overall odds ratio for the 19 studies of 1.29 (95% CI 1.01-1.67)., Conclusions: The overall odds ratio of 1.29 was statistically significant at the 5% level. These results may be useful for counseling ART patients and properly designing the consent forms used for ART procedures. It is not clear whether this risk is due to the procedures used in ART. We found that some of these studies have design flaws. All of them lacked an appropriate control group, i.e. infertile patients conceiving spontaneously. These flaws may create biases that would in almost all instances increase the risk of major malformations in the study group. Further research with better designed studies will likely result in a better estimate of the risk of major malformations associated with IVF and ICSI.

Purpose: Our purpose was to select the proper chromosomes for preimplantation diagnosis based on aneuploidy distribution in abortuses and to carry out a feasibility study of preimplantation diagnosis for embryos using multiple-probe fluorescence in situ hybridization (FISH) on the selected chromosomes of biopsied blastomeres., Methods: After determining the frequency distribution of aneuploidy found in abortuses, seven chromosomes were selected for FISH probes. Blastomeres were obtained from 33 abnormal or excess embryos. The chromosome complements of both the biopsied blastomeres and the remaining sibling blastomeres in each embryo were determined by FISH and compared to evaluate their preimplantation diagnostic potential., Results: Chromosomes (16, 22, X, Y) and (13, 18, 21) were selected on the basis of the high aneuploid prevalence in abortuses for the former group and the presence of trisomy in the newborn for the latter. Thirty-six (72%) of 50 blastomeres gave signals to permit a diagnosis. Diagnoses made from biopsied blastomeres were consistent with the diagnoses made from the remaining sibling blastomeres in 18 embryos. In only 2 of 20 cases did the biopsied blastomere diagnosis and the embryo diagnosis not match., Conclusions: If FISH of biopsied blastomere was successful, a preimplantation diagnosis could be made with 10% error. When a combination of chromosome-13, -16, -18, -21, -22, -X, and -Y probes was used, up to 65% of the embryos destined to be aborted could be detected.

Objective: To describe an investigation of the feasibility of carrying out polymerase chain reaction (PCR) and fluorescent in situ hybridization on the same single human cell for sex determination., Design: To develop protocol for a clinical diagnostic test in preclinical trials., Setting: Infertile human volunteers in a clinical environment., Patients: Polyploid embryos were obtained from patients treated by IVF at the Advanced Institute of Fertility., Interventions: Seventeen blastomeres biopsied from human polyploid embryos were analyzed for sex determination by simultaneous application of PCR and fluorescent in situ hybridization., Main Outcome Measure: Presence of an X- or X and Y-chromosome band after agarose gel electrophoresis of PCR products and presence of an X- or X and Y-chromosome fluorescent probe signal after fluorescent in situ hybridization following PCR analysis., Results: By PCR, all 17 blastomeres were amplified and, by fluorescent in situ hybridization, 12 (70.6%) blastomeres produced signals that were consistent with PCR results. Two blastomeres showed only X signals, although by PCR they had both X and Y-chromosome bands., Conclusions: The sequential use of PCR and fluorescent in situ hybridization on the same blastomere can be applied to improve the accuracy of sex determination before fresh ET.

Objective: To document the absence of oocytes in follicular aspirates in women who, during controlled ovarian stimulation with gonadotropin-releasing hormone agonist (GnRH-a) and menotropins, fail to receive human chorionic gonadotropin (hCG) administration., Design: Retrospective analysis of clinical laboratory data., Setting: Multicentric., Patients: Five women undergoing controlled ovarian hyperstimulation with GnRH-a and menotropins for programs of assisted reproductive technologies., Results: The documented absence of an hCG injection produced "empty follicles" at transvaginal guided aspiration, despite numerous follicular lavages and aspiration of peritoneal fluid. The lack of oocytes and granulosa-cumulus complex in the follicular fluid was reverted in other cycles in the same patients when hCG was properly administered., Conclusions: (1) This study emphasizes the importance of proper patients' and nurses' instructions for preparation of hCG injections and proper mixture of vehicle and powder before follicular aspiration. (2) In the absence of cumulus-corona-oocyte complex at aspiration, measure serum beta-hCG to ascertain whether hCG injection was administered or not. (3) Routine preoperative beta-hCG levels may be helpful to avoid unnecessary surgeries.

In order to improve the pregnancy rate per oocyte retrieval while reducing the chance of multiple-gestations, a technique of cryopreservation of human embryos was used for our initial study consisting of 100 infertile patients undergoing in vitro fertilization (IVF) procedure. These patients combined a "fresh" embryo transfer with cryopreservation. The embryos were cryopreserved with 1,2-propanediol. Twenty-nine (29%) patients achieved ongoing pregnancies from the fresh embryo transfer. Thirty patients received a transfer of thawed embryos in a natural cycle. Nine of these patients achieved ongoing pregnancies. Combining these 2 transfers results in a 38% ongoing pregnancy rate. Forty-one patients have yet to receive their frozen embryos. The current success rate in this study indicates that over 50% of the patients in this group can expect to become pregnant by the time all the cryopreserved embryos have been transferred.

Forty-two cases of pre-invasive and invasive cancer of the cervix diagnosed by histology were studied cytologically and cytogenetically. Preinvasive lesions showed a good correlation between cytologic impression and the histologic diagnosis. However, among 17 patients with invasive cancer, there were 2 completely negative cytologic impressions. These were in cases having modal chromosome counts of 47 and 48, respectively. This study demonstrates that some invasive cancers of the cervix are resistant to cytologic diagnosis because of their peridiploid chromosome counts and lack of anisokaryosis.

The administration of estrogens for gonadal dysgenesis is sometimes associated with the development of endometrial neoplasms. An approach which minimizes the inadvertent side effects while still providing the desired therapeutic effects may be to imitate the hormonal milieu of the normal menstruating woman. Oral administration of estradiol will not necessarily accomplish this, because of the intestinal conversion of estradiol to estrone. That problem can be overcome by the vaginal administration of estrogens.

Although gonadoblastoma is known to be associated with the presence of a Y chromosome, this case report of a 15-year-old patient with gonadal dysgenesis, gonadoblastoma, and an idic(Xq-) chromosome provides evidence for the occurrence of gonadoblastoma even in the absence of a Y chromosome. A review of previous cases reported to have gonadoblastoma in the absence of a Y chromosome revealed that the presence of some breast development was the common denominator among those patients. Therefore, a patient who presents with gonadal dysgenesis with some breast development, but lacks a Y chromosome may observe as close scrutiny as the patient with gonadal dysgenesis in the presence of a Y chromosome.

The present study reviews the pregnancy outcome of 99 patients treated with salpingostomy techniques for distal fimbrial obstruction. Eighty-seven patients were treated with terminal salpingostomy, 10 with medioampullary salpingostomy, and 2 with isthmic salpingostomy. The pregnancy rates were 28%, 20%, and 0%, respectively. Within the terminal salpingostomy group, 5 of 18 patients treated with a prosthesis conceived, for a pregnancy rate of 28%. Nineteen of the 69 patients treated with an eversion technique conceived, for a pregnancy rate of 28%. No advantage with the use of a terminal prosthesis could be demonstrated. Tubal disease treated with techniques of salpingostomy was categorized according to a classification incorporating the several prognostic factors thought to influence subsequent conception. The pregnancy rate was found to be in direct relationship to the extent of tubal disease and pelvic adhesion formation. The tubal patency rate decreased in direct relationship to the extent of disease. The use of postoperative hydrotubation did not appear to improve the conception rate after salpingostomy for distal fimbrial obstruction.

A common problem encountered by in vitro fertilization (IVF) programs is the premature occurrence of the spontaneous luteinizing hormone (LH) surge during ovarian stimulation cycles. Administration of gonadotropin-releasing hormone agonists (GnRH-a) for 2 to 3 weeks produces a state of hypogonadotropic hypogonadism, thus allowing ovarian stimulation to proceed uncomplicated by a spontaneous LH surge. We have elected to treat seven patients with GnRH-a in a "short-term" protocol, with GnRH-a initiated on cycle day 3 along with exogenous gonadotropins. In this series, we found that the spontaneous LH surge was abolished, while ovarian responsiveness seemed to be improved. These results suggest that the initial surge of gonadotropins elicited by GnRH-a administration may enhance ovarian stimulation and that spontaneous LH surge is blocked when GnRH-a and exogenous gonadotropins are initiated concomitantly.

Pregnancies achieved by IVF and resulting in blighted ovum were karyotyped. The rate of aneuploidy was found to be 38% (5/13). In vitro fertilization does not appear to be a risk factor for chromosome anomaly in live births or miscarriages, and the data reported so far may suggest that aneuploid rates are actually lower for pregnancies achieved by IVF.

In at least 4 of 7 cases, fertilization of intact human oocytes was more successful when spermatozoa were pretreated with TEST yolk medium at 5 degrees C for 2 hours as compared with the standard treatment with Ham's F-10 only. Both pregnancies that were obtained after the transfer of the fertilized oocytes resulted from oocytes fertilized by TEST yolk-treated spermatozoa. No decrease in fertilization occurred in any of the cases after TEST yolk treatment. If these results hold true for a larger series of patients, it may be worthwhile for the standard IVF incubation system of spermatozoa to include TEST yolk.

Since the rate of pregnancy is a function of time, conventional pregnancy rates (number of patients achieving pregnancy per number of patients treated) are inadequate for counseling unless the follow-up period is specified. To overcome this problem, the expectancy of pregnancy for 636 cases of primary infertility was calculated with the assumption that the patients were followed up indefinitely. The overall "conventional" pregnancy rate was 38%, whereas the overall expectancy of pregnancy was 64%. Endometriosis was found to be the most common factor, comprising 25% of the cases, with a pregnancy rate of 31% and an expectancy of 52%. The expectancy of future pregnancy in a patient who has not achieved pregnancy by a given time is presented for each etiologic factor. This paper also presents a comparison of expectancies of pregnancy by different treatments, which may be helpful in selecting appropriate therapy.

Sixty-four patients who had infertility associated only with endometriosis were treated with methyltestosterone, 5 mg/day, continuously for a period of 6 months. The patients continued to ovulate while receiving medication and 12 patients became pregnant, on an average, 6 months after the initiation of therapy. A computer analysis indicated that approximately 30% of the patients could expect pregnancy within 2 years after the testosterone treatment was begun. The side effects of the low-dose methyltestosterone therapy were acne in 6% of the patients, mild hirsutism in 3%, and an occasional delay in ovulation.

In search of a simpler and less traumatic method of oocyte retrieval for in vitro fertilization (IVF), 37 infertile patients underwent ultrasound-guided transvaginal needle aspiration of the follicles instead of the conventional laparoscopic aspiration. Although only intravenous analgesics and sedatives were used, patients experienced little discomfort. There were no infections or bleeding complications after the procedure. Eleven patients (30%) achieved ongoing pregnancies; this rate of success is comparable to that with our laparoscopic method. Considering this reasonable pregnancy rate, lack of substantial morbidity, and good patient acceptance, laparoscopic oocyte retrieval for IVF can be largely replaced by the ultrasound-guided transvaginal needle aspiration technique.

Historical data from 26 638 20-to 40-year women were used to study the association between obesity and menstrual abnormalities including evidence of infertility. It was found that women with evidence of anovulatory cycles, ie, irregular cycles greater than 36 days, and hirsutism, were more than 30 lb (13.6 kg) heavier than women with no menstrual abnormalities after adjusting for height and age. The percentage of women with evidence of anovulatory cycles was 2.6 per cent for women less than 20 per cent overweight, 4.0 per cent for women 20-49 per cent overweight, 5.8 per cent for women 50-74 per cent overweight., and 8.4 per cent for women more than 74 per cent overweight Women with a single menstrual abnormality including cycles greater than 36 days, irregular cycles, virile hair growth with facial hair, or heavy flow were also significantly heavier than women with normal values for these factors. A longer duration of obesity was associated with facial hair. Another analysis found that teenage obesity was greater for never-pregnant married women than for previously pregnant married women and for women having ovarian surgery for polycystic ovaries than for women having ovarian surgery for other reasons. This also supports an association of obesity with anovulatory cycles. These findings showing evidence of abnormal ovulation, menstrual abnormalities and excess hair growth in obese women may be explained by the recent studies of others demonstrating an association between obesity and hormonal imbalances.

A rare but typical case of trisomy 9 mosaicism is reported. The infant showed the characteristic phenotype of this syndrome: low-set malformed ears, micrognathia, broad nose with bulbous tip, abnormal brain, congenital heart disease, abnormal hands and feet, cryptorchidism, micropenis, and early death. This infant, however, did not have dislocation of joints or microcephaly; the head was larger than normal and had almost a cloverleaf shape.

Five hundred amniocenteses were carried out at midtrimester for prenatal diagnosis. A 22-gauge spinal needle with a stylet was used. The needle was guided by a real-time sector ultrasonograph. A transducer was placed adjacent to the puncture site and the needle tip was observed entering the amniotic cavity. By this technique, a bloody tap was avoided. There were only three (0.6%) spontaneous abortions in this group of 496 patients. Amniocentesis guided by ultrasound is a safe method for the mother and the fetus.