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The efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques.

OBJECTIVE: To evaluate the efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques (ARTs). DESIGN: Retrospective review of medical records and health care costs. SETTING: Tertiary care academic medical school ART program. PATIENTS: For determination of the efficacy of cryopreserved ET, we analyzed 610 patients undergoing the first 1,000 oocyte retrievals in our program. For determination of cost effectiveness, we analyzed the costs associated with 334 initiated ART cycles in 1992. MAIN OUTCOME MEASURES: The ongoing pregnancy rate (PR) per initiated cycle and per oocyte retrieval. The medical costs associated with each procedure. RESULTS: The transfer of cryopreserved embryos increased the ongoing PR per oocyte retrieval by 6.6%. Transfer of cryopreserved embryos was cost effective compared with other ARTs. The cost per delivery for cryopreserved ETs was between 25% and 45% that of a fresh cycle. CONCLUSIONS: Including embryo cryopreservation in an ART program can improve PRs and lower the ultimate cost per delivery.

Cost-Benefit Analysis↗

Serological testing for celiac disease in women undergoing assisted reproduction techniques.

BACKGROUND: The assertion of a causal relationship between celiac disease and infertility is suggested by several lines of research. Nevertheless, robust evidence has not yet been provided. The present study evaluated, for the first time, the prevalence of celiac disease in women undergoing assisted reproduction techniques (ART). METHODS: Serum samples from 200 Italian women undergoing ART were evaluated for celiac disease by endomisium antibody (EMA) and transglutaminase antibody (t-TGA)-two highly sensitive and specific serological markers. Two hundred women not reporting reproductive problems and having delivered at least one child served as controls. In cases of positive serology, the diagnosis was confirmed by jejunal biopsy. RESULTS: Five (2.5%) women from the study group and two (1.0%) from the control group were found to have celiac disease (P = 0.44). The main indications for ART in women found to have celiac disease were tubal factor in two cases and male infertility in three cases. None of these women reported major gastrointestinal complaints. Extra intestinal signs linked to celiac disease were noted in four out of five patients. CONCLUSION: This study raises the issue of celiac disease screening in ART programmes. Given the available evidence in the literature combined with our observations from this study, the value of serological testing for celiac disease in infertile women remains uncertain. Further studies to address this issue are required.

Adult↗

[Genetic engineering and assisted reproduction techniques in man: a framework for sociologic analysis].

The possibilities opened up by genetic engineering and assisted reproduction techniques require reflection by sociologists and extensive public debate. In view of their potential as factors of social change, evaluation and control are warranted. They can be viable only if transparent and through public co-responsibility, for which an exchange of views is needed between all those who play a part in the development of said techniques. This dialogue must be wholly interdisciplinary and democratic.

Forecasting↗

Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique.

BACKGROUND: Standard sperm characteristics are poor predictors of the outcome of IVF treatments. On the contrary, sperm genome quality has been emphasized for several years as playing a major role in early embryogenesis, thus in the success of IVF attempt. METHODS: Sperm DNA fragmentation from a selected group of 104 couples undergoing assisted reproductive techniques (ART) (IVF: n = 50; and ICSI: n = 54) was measured by TUNEL assay and correlated with semen and ART outcomes. RESULTS: A negative correlation was found between sperm characteristics and the proportion of sperm showing DNA fragmentation. For fragmentation >10%, a significant decrease of the fertilization rate was observed. No correlation was found between sperm DNA fragmentation and embryo quality. A high proportion of sperm with fragmented DNA was a pejorative factor to obtain pregnancies when ICSI was performed, but there was no relationship when conventional IVF was performed. CONCLUSIONS: The proportion of sperm with DNA fragmentation appears to be potentially useful as a predictor of ICSI outcome, whereas embryo quality based on morphological criteria, appeared unaffected by DNA fragmentation.

DNA Fragmentation↗

Intra-follicular leptin concentration as a predictive factor for in vitro oocyte fertilization in assisted reproductive techniques.

BACKGROUND: Granulosa-cells are able to produce and store leptin, suggesting that this hormone is locally involved in the regulation of follicular growth. In this study, the role of follicular fluid (FF) leptin concentration in predicting oocyte fertilization and embryo quality was evaluated in 35 normogonadotrophic women undergoing controlled ovarian stimulation (COS) for assisted reproductive techniques. MATERIALS AND METHODS: Leptin concentration was measured in 47 consecutively collected FF in which a mature oocyte had been found during the ovum pick-up. Embryos deriving from fertilized oocytes were submitted to quality scoring systems. RESULTS: Mean leptin concentration was significantly higher in FF whose oocytes showed 2 pronuclei (no. 25) when compared with those with no evidence of fertilization (no. 22) at the 16-18 h check (26.0+/-6.1 vs 15.3+/-10.6 ng/ml, respectively, p<0.01). Follicular mean diameters were similar in the two groups (21.4+/-3.4 and 21.0+/-5.1 mm, respectively). Logistic regression analysis identified FF leptin levels as the best predictive parameter for oocyte fertilization (p<0.001). When receiving operating characteristics curve was employed, a FF leptin concentration of 20.25 ng/ml was the most reliable cut-off in predicting fertilization of oocytes. FF with leptin concentrations higher than this value (no. 27) had an oocyte fertilization rate of 85.7%. In contrast, FF levels < or =20.25 ng/ml (no. 20) were associated with a rate of 16.7% (p<0.05). No correlation emerged between FF leptin and the score attributed to 15 valuable embryos at the zygote stage (r=-0.01) and at 48 h after insemination (r=0.1). CONCLUSIONS: FF leptin levels are a better predictor of oocyte fertilization success rates than follicular diameter. These results underline the relevance of FF variables in developing methods for oocyte selection.

Adult↗

Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques.

BACKGROUND: This study analyses the prevalence of karyotype changes and Yq11 microdeletions among couples referred for assisted reproduction techniques. METHODS: Prior to receiving either IVF or ICSI treatment, each partner of 2078 infertile couples was screened for karyotype changes by GTG-banding technique on peripheral lymphocytes. No subject presented with obvious phenotype of chromosomal rearrangement. All the oligo/azoospermic men with normal karyotype were further investigated by PCR for Yq11 microdeletions. RESULTS: Eighty-two out of 2078 couples (3.95%) had one partner carrying a chromosomal change, and 10 out of 202 (4.95%) men showed Yq11 microdeletions. The chromosomal rearrangements were 44 (2.1%) translocations, 23 (1.1%) gonosomal mosaics, six (0.3%) 47,XXY, five (0.24%) marker chromosomes, three (0.14%) inversions and one (0.05%) duplication. Frequency of anomalies in men and women were similar: 42 and 40 cases respectively. CONCLUSIONS: Partners of infertile couples requiring IVF or ICSI treatment appear to be affected by higher frequency of chromosomal rearrangements than the general population. Categories with greater risk were represented by men with sperm cell count <20 x 10(6) sperm/ml, and women with history of pregnancy loss.

Adult↗

Course of ovarian hyperstimulation syndrome in 19 intact twin pregnancies after assisted reproduction techniques, with a case report of severe thromboembolism.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproduction techniques using in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI). Its etiology has still not yet been fully resolved. Human chorionic gonadotrophin, administered exogenously as well as produced endogenously during pregnancy, is responsible for the onset of OHSS, and high levels of estradiol appear to worsen the condition. In this case series, the course of mild to severe OHSS was evaluated in 19 intact twin pregnancies after IVF/ICSI. Another serious complication associated with OHSS is thromboembolic events. In these cases, the pregnancy can be protected through anticoagulation treatment, but there may be exceptions to this. This series includes a case of bilateral thrombosis of the internal and external jugular veins in the 7th gestational week in a twin pregnancy after OHSS and ICSI, with termination of the pregnancy in the 9th gestational week due to progressive thrombosis during anticoagulation therapy.

Adult↗

Investigation into effectiveness of counseling on assisted reproductive techniques in Turkey.

This experimental study was conducted to determine the specific problems experienced by couples participating in assisted reproductive techniques (ART) and to assess couples' counseling needs. It was also intended to determine the effects of the counseling service model, developed and implemented by the researcher, on the success rate of ART, and to assess the couples' anxiety, depression and life satisfaction levels. Thirty couples for the experimental group and 30 couples for the control group were included in the study. The couples in the control group experienced the routine procedures that the treatment currently includes. Couples in the experimental group took part in the counseling service model, and were informed and supported throughout the steps of the ART A guide developed for the couples and education material developed for the counseling service model were used during the study. Three psychological tests were given to the couples before (pretest) and after (post-test) each procedure. These tests included anxiety, depression and life satisfaction inventories. The difference means test and Student's t test were used for statistical analysis. The results of the study showed that couples in the experimental group had lower anxiety and depression scores than the couples in the control group. Life satisfaction scores and pregnancy rates were higher for couples in the experimental group than for the couples in the control group. Statistical evaluation showed that the difference between the experimental group and the control group was significant (p < 0.05). This study demonstrates the importance of the counseling role of the nurse, and the development and application of counseling services in ART centers, in lowering the anxiety and depression levels of couples and ensuring success of the treatment.

Adaptation, Psychological↗

[The Constitutional Court regarding Assisted Reproduction Techniques: a critical assessment].

Last June Spain's Constitutional Court ruled on the challenge lodged against Law 35/1988 on Assisted Reproduction Techniques (Ruling 116/1999). The ruling confirmed the provisions of the Law. However, in examining the Law in question the Court did not, in my opinion interpret correctly the Spanish Constitution. I argue that there are three main areas of disagreement: since the contents directly affect human dignity the Law should have taken the form of a higher (Organic) Law. Secondly, the Law's treatment of in vitro fertilised embryos in certain cases, falls short of the minimum required by the Constitution. Thirdly, paternity investigation is prevented contrary to the provisions of the Constitution and hence the constitutional notion of family is undermined.

Family↗

Inhibition of oocyte fertilization by assisted reproductive techniques and increased sperm DNA fragmentation in the presence of Candida albicans: a case report.

The effects of Candida albicans on sperm parameters and the outcome of infertility treatment are unclear. This report describes a lack of fertilization after assisted reproductive techniques and increased sperm DNA fragmentation in an infertile patient with male accessory gland infection due to Candida albicans. He had normal sperm parameters and, therefore, underwent conventional IVF for a female factor of infertility. No spermatozoa or only one spermatozoon per oocyte were found attached to the zona pellucida of the six mature oocytes retrieved. A new semen sample was then requested from the patient to perform intracytoplasmic sperm injection (ICSI) on the same oocytes, but again no fertilization resulted. Candida albicans was detected in the medium where spermatozoa were co-incubated with oocytes and subsequently in the urethral swabs. It did not have any detrimental effect on sperm parameters soon after ejaculation or following separation of motile spermatozoa by swim-up technique. Fertilization failure after assisted reproduction treatment was associated with an increased percentage of motile spermatozoa having chromatin packaging abnormalities, externalization of phosphatidylserine and DNA fragmentation. In conclusion, Candida albicans did not affect sperm parameters, but increased sperm chromatin packaging damage and apoptosis that might have caused fertilization failure after assisted reproduction treatment in this couple.

Adult↗

The effects of oxidative stress on outcomes of assisted reproductive techniques.

PURPOSE: To investigate the impact of oxidative stress on pregnancy success by monitoring malondialdehyde levels in follicular fluid. METHODS: Forty five couples were enrolled in this prospective study. Following long protocol of GnRH analogues and r-FSH treatment, oocyte retrieval and intracytoplasmic sperm injection were performed. Malondialdehyde levels were assayed by thiobarbutiric acid reacting substances test. Student's t-test and chi(2) test were used for statistical analysis. RESULTS: Patients were divided into two groups; group I (pregnancy positive, n = 20), group II (pregnancy negative, n = 25). There was no statistical significant difference in terms of age, infertility period, FSH levels on the third day, number of oocytes retrieved and fertilization rates between the two groups. Pregnancy rates were found to be decreasing in higher malondialdehyde levels. CONCLUSION: Malondialdehyde can be used as a marker of oxidative stress and a potential marker in predicting assisted reproductive techniques outcome.

Adult↗

Results of assisted reproductive technique in men with cystic fibrosis.

BACKGROUND: Sterility in men with cystic fibrosis (CF) raises the question of the use of assisted reproductive techniques (ART). A multidisciplinary network including adult CF centre and reproductive medicine units was set up to answer requests for ART. METHODS: This retrospective study included 25 men with CF between 1994 and 2004. Clinical status, semen analysis, CF mutations analysis and artificial insemination by donor (AID) or ICSI after surgical retrieval of sperm were monitored. RESULTS: All CF men had azoospermia. Two chose AID first (one delivery); 23 chose ICSI. Sperm were surgically retrieved in 21 cases, and ICSI was performed in 19. Pregnancies occurred in 12 of these 19 couples (63%) (two ectopic pregnancies, two spontaneous abortions, one termination of pregnancy for polymalformed twins and 11 single deliveries in nine couples). Two couples tried AID after ICSI failed; one had twins. Another adopted a child, and two had a spontaneous pregnancy. After a follow-up of 4.1+/-2.3 years, two patients died, two underwent lung transplantation and 21 remained stable. CONCLUSION: ART can help men with CF to become a father, but their health status and short survival need careful counselling and multidisciplinary medical care.

Cystic Fibrosis↗

Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review.

OBJECTIVE: To summarize the existing experience with the use and success rate of assisted reproductive techniques (ART), in particular testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI), in Klinefelter patients. DESIGN: A systematic review of the literature, including all published case reports to date. PATIENT(S): Thirty-nine reported successful pregnancies fathered by nonmosaic Klinefelter patients. MAIN OUTCOME MEASURE(S): The overall risk of transmitting a chromosomal abnormality to the offspring of Klinefelter patients. RESULT(S): In nonmosaic and mosaic Klinefelter patients, chromosomally normal sperm cells can be extracted from testicular tissue and used for ICSI. CONCLUSION(S): The application of ART to Klinefelter patients can be recommended as a method to achieve reproduction in this selected infertility patient cohort.

Chromosome Aberrations↗

[Genetic reading of the decision of the Constitutional Court on the appeal on unconstitutionality against Law 35/1988 on Assisted Reproduction Techniques].

In this article we provide a "genetic reading" of the challenge on grounds of alleged inconstitutionality made against Spain's Law on Assisted Reproduction Techniques (Law 38/1988) and of the ruling handed down by the Constitutional Court on 17 June 1999. A critical appraisal is given of some genetic and biological concepts which, in the author's view, are used incorrectly in the legal texts presented. The article also shows that at the heart of the matter lies still the latent problem of the status in law of embryos. Lastly, brief reference is made to the issue of freedom of research.

Embryo, Mammalian↗

In vitro fertilization and other assisted reproductive techniques.

Each year, thousands of pregnancies are achieved worldwide by in vitro fertilization (IVF) and its modifications, commonly grouped under the general term "assisted reproductive techniques" (ARTs). The IVF program at the University of Southern California (USC) was among the first to be established in the United States and had the distinction of achieving success, in 1981, with the first IVF infant to be born on the West Coast. This paper discusses patient selection, superovulation techniques, methods of follicle aspiration, sperm preparation, embryo transfer procedures and management of the luteal phase of ART cycles. The various ARTs are described, as are the expected success rates. Particular emphasis is placed on the techniques of oocyte donation and unstimulated IVF, both of which play prominent roles in the treatment of infertility in the USC program.

Fertilization in Vitro↗

Epididymal sperm aspiration with assisted reproductive techniques: difference between congenital and acquired obstructive azoospermia?

From July 1992 to May 1994, 31 cases of obstructive azoospermia-induced infertility underwent 35 epididymal sperm aspiration procedures and assisted reproductive techniques. These included in-vitro fertilization (IVF), zygote intra-Fallopian transfer (ZIFT), subzonal insemination (SUZI) and intracytoplasmic sperm injection (ICSI) with embryo transfer or tubal embryos transfer. The motile spermatozoa were retrieved using a gauge 24 Medicut cannula and flush medium. Total oocyte fertilization rate was 23.4% and the clinical pregnancy rate was 12.5% (four out of 32 treatment cycles). Congenital absence of the vas deferens was found in 16 cases (51.6%) and secondary genital duct obstruction was present in 15 cases (48.4%). In all, 29 aspirations were retrieved from the caput of the epididymis and six from the epididymal body or tail. The fertilization rate for the caput spermatozoa was much less than that for other areas of the epididymis (P < 0.05). Though there were no predictable differences in fertilization rates between the congenital and acquired groups, by using epididymal spermatozoa for assisted reproduction, the congenital group seemed to have a stronger tendency to achieve pregnancy (20 versus 5.9%).

Adult↗

Outcome of triplet pregnancies after assisted reproductive techniques: how frequent are the vanishing embryos?

OBJECTIVE: To assess the incidence of spontaneous embryo reduction as well as the obstetric and neonatal outcome of triplet gestations after assisted reproductive techniques (ART). METHODS: We analyzed the spontaneous outcome of 38 pregnancies in which three gestational sacs were identified with vaginal ultrasound between 21 and 28 days after ART. Weekly follow-up visits were scheduled during the first trimester until referral to a high-risk obstetrician. After delivery, each patient was interviewed individually and, if necessary, the obstetrician was contacted. RESULTS: The triplets delivery rate was 47.4%, whereas 31.6% delivered twins, 18.4% delivered singletons, and only one patient miscarried all three cases (2.6%). Finding three fetal heart beats was associated with a triplet delivery rate of 69.2%, a twin incidence of 19.2%, and a singleton birth rate of 11.6%. Embryo resorptions were observed mainly during the first 7 weeks of gestation and did not occur beyond the 14th week. The mean gestational age at delivery and neonatal birth weight were significantly lower among triplets (32.8 weeks and 1,740 g versus 35.3 weeks and 2,352 g in twins and 39.1 weeks and 3,122 g for singletons). Triplets had a 100% prematurity and cesarean section rate compared with 67% and 75% in twins and 0% and 43% in singletons, respectively. Hospitalization at the Neonatal Intensive Care Unit was required in 83% of newborn triplets, 29% of twins, and 0% of singletons, with a mean stay of 34 and 21 days for triplets and twins, respectively. One stillbirth and no neonatal deaths were reported, with an overall perinatal mortality rate of 11.9 per 1,000. CONCLUSIONS: Spontaneously, approximately 50% of triplet pregnancies will experience at least one embryo resorption. The ongoing triplets demand a complex and more expensive perinatal management, a strong argument to consider limiting the number of oocytes-embryos transferred in ART.

Birth Weight↗

Critical evaluation of human blastocysts for assisted reproduction techniques and embryonic stem cell biotechnology.

Critical examination of 30 blastocysts by transmission electron microscopy (TEM) reveals cellular features not usually evident, including abnormalities of cell structure and aberrations such as multinucleation, internal fragmentation, phagocytic or degenerating cells. Invariably, such blastocysts are inactive and delay or fail to expand and hatch in vitro. Hatching seems to be a major problem in ageing blastocysts due to inactivity of the surface epithelium of trophoblast cells that do not stretch and expand. These lack surface microvilli and contractile tonofilaments that anchor on to specialized cell junctions such as desmosomes. Trophoblast expansion and consequent thinning of the zona is a prerequisite to proper hatching aided by the hydrostatic pressure in the blastocoele and by specialized cells at hatching points. Proper assessment of the inner cell mass is required if a healthy population of cells is to be harvested for embryonic stem cell culture. An inactive blastocyst is obviously not good material and could have a defective inner cell mass (ICM). Normally approximately 3-5% of cells are mitotic in blastocysts and arrested cell division is also an indicator of inactivity. An attempt has been made to evaluate blastocyst internal structure for both assisted reproduction techniques and embryonic stem cell biotechnology.

Biotechnology↗