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PubMed2004

Drug intervention in early pregnancy after assisted reproductive technology.

Implantation in humans is a complex, closely regulated, highly selective and relatively poorly understood process. Humans have the highest rate of miscarriage in mammals and various pharmacological manipulations have been used to minimize pregnancy losses in both spontaneous pregnancies and pregnancies resulting from assisted reproduction technology. The widespread application of protocols using numerous drugs in assisted reproduction treatment has led to an increasing number of pregnancies exposed to these drugs. The vast majority of these protocols have been based on data from a few observational and often retrospective clinical studies. This paper reviews the recent literature on drug interventions in early pregnancy after assisted reproduction treatment. It is concluded that there are still numerous issues about the safety of most drugs for both the women and their fetus. In many cases, the benefits are theoretical and the possible long-term side-effects are untested. There is an urgent need for more epidemiological studies and randomized controlled trials to explore the use, efficacy and side-effects of both old and new drugs in early pregnancy after assisted reproduction treatment.

Abortion, Habitual↗
PubMed2003

Community attitudes to assisted reproductive technology: a 20-year trend.

OBJECTIVE: To review the results of opinion polls on community attitudes to in-vitro fertilisation (IVF) and other aspects of assisted reproductive technology over a 20-year period. DESIGN, SETTING AND PARTICIPANTS: Fourteen Australia-wide interview surveys that included questions relating to IVF were carried out between July 1981 and November 2001 as part of regular Morgan polls of community attitudes on various topics. Each survey involved about 1000 respondents drawn from randomly selected "cluster points" in urban and rural locations. MAIN OUTCOME MEASURES: The proportion of people who approved or disapproved of various aspects of IVF treatment. RESULTS: Support for IVF to help infertile married couples increased from 77% in 1981 to 86% in 2001. Approval for IVF procedures being supported by Medicare funding rose from 70% in 1981 to 79% in 2000. CONCLUSIONS: Community approval of the use of IVF to treat infertility has risen significantly in Australia over the past 20 years.

Adolescent↗
PubMed2001

Is tubal embryo transfer of any value? A meta-analysis and comparison with the Society for Assisted Reproductive Technology database.

OBJECTIVE: To analyze published randomized trials of ZIFT and ET via meta-analysis and compare the results with those of the Society for Assisted Reproductive Technology database. DESIGN: Meta-analysis and comparison to SART data sets for 1991-1996. SETTING: University medical center. PATIENT(S): Patients from the literature with infertility, randomized to either tubal or uterine embryo transfer. INTERVENTION(S): All published articles in English were identified using an electronic database spanning January 1966 to December 1998 by keyword and text word searches, supplemented with a hand search through the references of original studies, review articles, and conference abstracts to identify randomized trials comparing ZIFT and IVF-ET. Additional data was obtained through correspondence with authors. MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rates were compared. Ectopic pregnancy rate was a secondary outcome measure. RESULT(S): Six randomized controlled trials including 548 cycles, 514 retrievals, and 388 transfers were reviewed. Demographic and stimulation and transfer details were comparable between the groups. Implantation and pregnancy rates did not differ significantly, and there was a trend toward increased risk of ectopic pregnancy with ZIFT. CONCLUSION(S): Published randomized trials suggest that there is no difference in implantation and pregnancy rates between women undergoing ZIFT and IVF-ET.

Databases, Factual↗
PubMed2000

Evaluation and treatment of low responders in assisted reproductive technology: a challenge to meet.

PURPOSE: To investigate the various methods of evaluation and treatment of patients with a low response to controlled ovarian hyperstimulation in assisted reproductive technologies (ART). METHODS: Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches. RESULTS: While a universally accepted definition for low responders is still lacking, these patients are reported to represent about 10% of the ART population. Several ovarian reserve screening techniques have been proposed; however, currently the best-characterized and most sensitive screening tools available are the basal day 3 serum follicle-stimulating hormone level and the clomiphene citrate challenge test. When abnormal, these tests allow physicians to counsel patients that their prognosis for conception is poor. Although the presence of a normal result does indicate better long-term chances for conception, on age-related decline in fecundity remains and patient age should still be considered when counseling patients with normal screening results. Several stimulation protocols have been applied in the low-response group with varying success. Recent studies show that the use of a minidose gonadotropin-releasing hormone-agonist protocol may result in significantly decreased cycle cancellations as well as increased clinical and ongoing pregnancies, and thus is proposed as a first-line therapy. Studies evaluating supplementary forms of treatment to the ovulation induction regimen show improved outcome when pretreating with oral contraceptives, whereas there seems to be no benefit from cotreatment with growth hormone or glucocorticoids. Blastocyst culture and transfer and assisted hatching in low responders are still under evaluation, whereas natural cycle in vitro fertilization may be used in cases of repeated failures as a last option before resorting to oocyte donation or adoption. Future possible forms of treatment like in vitro maturation of immature human oocytes, cytoplasm, and nuclear transfer currently are experimental in nature and their efficacy has still to be proven. CONCLUSIONS: The evaluation and treatment of low responders in ART remains a challenge. Understanding of the underlying etiology and pathophysiology of this disorder may help the clinician to approach it successfully.

Adult↗
PubMed2005

The legal aspects of parental rights in assisted reproductive technology.

This paper provides an overview of the different legal approaches that are used in various jurisdictions to determine parental rights and obligations of the parties involved in third party assisted reproduction. Additionally, the paper explores the differing legal models that are used depending on the method of surrogacy being utilized. The data demonstrates that a given method of surrogacy may well result in different procedures and outcomes regarding parental rights in different jurisdictions. This suggests the need for a uniform method to resolve parental rights where assisted reproductive technology is involved.

Contracts↗
PubMed1997

A medico-legal evaluation of the use of assisted reproductive technologies in Turkey.

In Turkey, as possibly in the case of several or even many other countries, infertility is generally regarded as a negative phenomenon in women. Assisted Reproductive Technologies (ARTs), which provide certain childless couples with the possibility of having a baby, are being applied more and more frequently in this country, apparently as has been the case in the world at large. From a medicolegal point of view, the related applications in Turkey can only be realized in the case of married couples. Other forms of application in this area, on the other hand, such as sperm banks or surrogate motherhood, are not allowed legally. A text which was called "Guidelines Regarding the Centers of In Vitro Fertilization and Embryo Transfer" was prepared in 1987 by the Ministry of Health. The aim of these Guidelines is to find solutions to the medico-legal problems created by the application of ARTs in this country.

Cross-Cultural Comparison↗
PubMed2005

The role of ketoconazole in the prevention of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during assisted reproductive technology cycles.

OBJECTIVE: To assess the clinical efficacy of ketoconazole (KCZ) as an inhibitory enzyme on ovarian steroidogenesis, in prevention of ovarian hyper- stimulation syndrome (OHSS) during assisted reproductive technology (ART) in patients with polycystic ovarian syndrome (PCOS). METHODS: We included 58 PCOS patients, enrolled for in-vitro fertilization or intracytoplasmic sperm injection in a randomized clinical trial between November 2000 and October 2001 in the Royan Institute, Tehran, Iran. Twenty-eight patients received KCZ during the stimulation phase and 30 patients were controls. We compared serum E2 levels, number of lead follicles, number of retrieved oocytes, fertilization rate, occurrence of OHSS and cancellation rate using student's t-test, Chi-square and Fisher exact test. RESULTS: We found no significant differences between the 2 groups in the peak serum estradiol level, the number of lead follicles, oocytes, and fertilization rate. One patient in the control group had clinical symptoms of severe ovarian hyperstimulation, and none from the treated group. CONCLUSION: This study reveals no significant effect of KCZ on the incidence of OHSS during ART cycles; however, also no significant negative effects of KCZ on the number and maturity of oocytes or on fertilization rate.

Adult↗
PubMed2004

Assisted reproductive technology and congenital overgrowth: some speculations on a case of Pallister-Killian syndrome.

We report on a boy with Pallister-Killian syndrome (PKS) who was conceived by assisted reproductive technology (ART), specifically in vitro fertilization (IVF) with parents' gametes. A prenatal diagnosis performed elsewhere by CVS failed to detect the presence of the isochromosome 12p that was demonstrated postnatally in approximately 50% of cultured skin fibroblasts. Given that the patient did not show the congenital overgrowth typical of PKS, we speculate that ART might have restricted overgrowth in this particular case. More broadly, we hypothesize that overgrowth might protect from early demise fetuses conceived by ART, a technology known to cause low and very low birth weight.

Abnormalities, Multiple↗
PubMed1993

Gamete intrafallopian transfer: ethical considerations, historical development of the procedure, and comparison with other advanced reproductive technologies.

OBJECTIVE: To report on ethical considerations regarding GIFT as well as the developmental history of the procedure and to review the literature and compare it with other advanced reproductive technologies (ARTs). DESIGN: Indications, patient screening, recent evaluations, methods of ovarian hyperstimulation and oocyte retrieval-assessment, gamete transfer and pregnancy outcome are discussed in this review. A comparison of GIFT with other ARTs is also attempted. MAIN OUTCOME MEASURES: Gamete intrafallopian transfer pregnancy determination and outcome. CONCLUSIONS: Gamete intrafallopian transfer is an ethically acceptable procedure by different religious groups. In a selected group of patients, GIFT is an acceptable and, in some occasions, a preferable procedure to other ARTs.

Biomarkers↗
PubMed2006

Predictive factors and a corresponding treatment algorithm for controlled ovarian stimulation in patients treated with recombinant human follicle stimulating hormone (follitropin alfa) during assisted reproduction technology (ART) procedures. An analysis of 1378 patients.

BACKGROUND: Identifying parameters that can accurately predict the response to controlled ovarian stimulation (COS) would be of great benefit in assisted reproductive technology (ART) procedures. An analysis was undertaken with the objective of determining whether specific factors could optimally predict a response to stimulation in ART, and to then develop a corresponding treatment algorithm that could be used to calculate the optimal starting dose of recombinant human follicle stimulating hormone (r-hFSH; follitropin alfa) for selected patients. METHODS: The overall population consisted of 2280 normo-ovulatory ART patients from 11 randomised clinical trials. However, for the final analysis population, only patients less than 35 years of age who received r-hFSH monotherapy (N = 1378) were included. RESULTS: Backwards stepwise regression modelling indicated that predictive factors for ovarian response included basal FSH, BMI, age and number of follicles < 11 mm at baseline screening. The concordance probability index was 59.5% for this model. CONCLUSIONS: In the largest data series so far analysed to determine predictive factors of ovarian response, basal FSH, BMI, age and number of follicles < 11 mm at screening were the most important variables in ART patients less than 35 years of age who were treated with r-hFSH monotherapy. Using these four predictive factors, a follitropin alfa starting dose calculator was developed that can be used to select the FSH starting dose required for an optimal response. The relevance of this dose calculator will be evaluated in a prospective clinical trial.

Adolescent↗
PubMed1999

Do placentae of term singleton pregnancies obtained by assisted reproductive technologies differ from those of spontaneously conceived pregnancies?

The study was conducted to investigate the association of placental morphological and histopathological features with term, singleton pregnancies obtained by assisted reproductive technologies (ART). The study group comprised 45 consecutive women with a singleton pregnancy, obtained by ART, who delivered at term. For each subject in the study group, the consecutive, matched-for-age-and-parity woman, with a term singleton, spontaneously conceived pregnancy served as the controls. The placentae of both groups were subject to a detailed morphological and histopathological investigation by one pathologist, who was blinded to specimen origin. Pregnancy complications, fetal weight and perinatal outcome were similar in both groups. No differences in morphological or histopathological features of the placenta were observed between the groups. Nevertheless, the placentae of the study group showed a borderline, significantly higher placental weight and placental:fetal weight ratio, and placental thickness was significantly higher. Abnormal umbilical cord insertion was significantly more prevalent in the study group. Neither the specific ART method employed, nor the infertility factor affected the results, suggesting that multiple embryo transfers and/or ovulation induction protocols may account for these differences.

Adult↗
PubMed1986

Infertility and the new reproductive technology: a role for social work.

Infertility affects 1 in 6 couples in the United States during their childbearing years. The causes are sociological, medical and environmental. The new reproductive technology such as in-vitro fertilization and the alternatives to biological parenting such as surrogate motherhood raise legal and ethical issues as they raise the hopes of those couples previously unable to have a baby. As expectations have risen and treatment options become more complex, the social worker has become an essential member of the treatment team.

Counseling↗
PubMed2000

Intracytoplasmic sperm injection in assisted reproductive technology: an evaluation.

Since the first reports of successful pregnancies in humans after treatment with intracytoplasmic sperm injection (ICSI), intensive investigations have focused on several important aspects of this form of assisted reproductive technology. In addition to the technical development of ICSI and increasing understanding of the biochemical and biophysical processes involved during fertilization after injection of an immobilized sperm, studies have aimed to define the indications for patients for a first-line ICSI treatment. One of the major concerns is of course the safety of the technique in terms of the health and reproductive life of the babies born after ICSI. The rhesus monkey is an excellent model to investigate all aspects of this micromanipulation technique. This article provides an evaluation of ICSI.

Journal Article↗
PubMed2005

Follicular fluid levels of vascular endothelial growth factor and early corpus luteum function during assisted reproductive technology cycles.

BACKGROUND: The relation between vascular endothelial growth factor (VEGF) and early luteal function has rarely been proven in humans. The purpose of this study was to define the relation between follicular fluid concentrations of VEGF (FF VEGF) and early luteal function at the preimplantation stage during assisted reproductive technology (ART) cycles. METHODS: 71 women were divided into two groups, based on reproductive outcome: women who became pregnant after embryo transfer (ET) (n = 18, Group A) and non-pregnant women (n = 53, Group B). Serum progesterone (Se P) and inhibin A on ET day, and FF VEGF levels were measured in all women. Data were expressed as mean +/- standard deviation. Statistical analysis was performed using Excel Office 98 for Student's t-test, linear regression test and chi-square test. A p value of < 0.05 was considered statistically significant. RESULTS: The groups were comparable for age, ovarian reserve, number and quality of the oocytes retrieved and of the embryos obtained and transferred. FF VEGF levels were increased (4235 +/- 1433 vs 3432 +/- 1231 pg/ml), while Se P and inhibin A levels were significantly reduced (83.1 +/- 34.1 vs 112.0 +/- 58.8 ng/ml and 397.4 +/- 223 vs 533.5 +/- 283 pg/ml, respectively) in the non-pregnant group and were negatively correlated with FF VEGF (r = -0.482, p < 0.05; r = -0.468, p < 0.05) only in pregnant women. CONCLUSION: Much has to be learned about the regulation and role of VEGF during the early luteal phase. We advance the hypothesis that the existence of a negative correlation between FF VEGF/Se P and FF VEGF/inhibin A in pregnant women might indicate the existence of a normal VEGF-mediated paracrine response when Se P and inhibin A levels are decreased. Excess production of FF VEGF and the absence of a correlation between FF VEGF/Se P and FF VEGF/inhibin A in non-pregnant women may be a paracrine reaction to immature luteal vasculature, resulting in luteal dysfunction.

Journal Article↗
PubMed1993

A novel ovarian stimulation protocol for use with the assisted reproductive technologies.

OBJECTIVE: To determine whether a new ovarian stimulation protocol termed "minimal stimulation" provides pregnancy rates (PRs) comparable with those in a conventional full stimulation protocol for patients undergoing assisted reproductive technologies (ART). DESIGN: Prospective, nonrandomized study of patients in minimal stimulation or full stimulation, followed by standard IVF and zygote intrafallopian transfer or uterine-ET. SETTING: The ART program of the Mayo Clinic, Rochester, Minnesota. PATIENTS: Women (n = 120) 42 years of age or younger with serum day 3 FSH level < or = 15.0 mIU/mL (conversion factor to SI unit, 1.0), normal thyroid-stimulating hormone and PRL levels, normal endometrial cavity as observed on hysterosalpingogram, and partners with a normal semen analysis. INTERVENTIONS: Oral clomiphene citrate, hMG, oocyte retrieval, IVF-ET. MAIN OUTCOME MEASURES: Cancellations, implantation, pregnancy. RESULTS: The cancellation rate was not significantly higher in minimal stimulation (25.8%) than in full stimulation (14.1%). Minimal stimulation cycles yielded fewer oocytes per aspiration (3.4 +/- 1.6) than full stimulation (10.1 +/- 5.4). There was no difference in the implantation rates per ET (minimal stimulation, 16.4%; full stimulation, 13.3%) or overall clinical PRs per retrieval (minimal stimulation, 31%; full stimulation, 42%). CONCLUSIONS: Minimal stimulation for IVF is less expensive than full stimulation and minimizes monitoring and patient discomfort. In addition, it produces acceptable PRs and represents an attractive alternative to select patients undergoing ART.

Adult↗
PubMed2002

From the Centers of Disease Control and Prevention. Use of assisted reproductive technology--United States, 1996 and 1998.

Since 1983, when the first infant was conceived from in vitro fertilization (IVF) in the United States, the use of IVF and related procedures (assisted reproductive technology [ART]) has increased substantially. In 1998, an estimated 0.7% of the 3.9 million births were the result of ART. ART patients are more likely to deliver multiple infants than women who conceive without treatment, and these multiple-infant births are associated with increased risks for pregnancy complications, premature delivery, low birth-weight infants, and long-term disability among surviving infants. This report examines state-specific use of ART in 1996 and 1998 and provides data on ART live-born and multiple-infant birth rates in 1998. Findings indicate that the use of ART is increasing in most states and that more than half the infants born as a result of these procedures are multiple births. These high-risk births contribute disproportionately to health-care costs and might negatively affect maternal and child health outcomes, particularly in states where large numbers of ART procedures are performed.

Adult↗
PubMedDate not supplied

[Should we apply assisted reproduction technology to women without limitations of age?].

The decline of female fertility with increasing age is due to a physiological diminution of the ovarian reserve of follicles. Hence, a reliable evaluation of the ovarian reserve before performing assisted reproductive technology in aged women provides them and the physician with information about the actual probabilities of pregnancy. Patients aged over 38 years should be accepted in assisted reproduction programs only after confirmation of a healthy ovarian reserve. Patients aged more than 42 years, even in case of a normal ovarian reserve assessment, should be only accepted in selected cases. After 42 years until 46 of age, techniques of in vitro fertilization with oocyte donation may represent an alternative chance of pregnancy to aged women.

Adult↗
PubMed2005

Heterogeneity, the masked part of reproductive technology success rates.

BACKGROUND: Heterogeneity in women and men's fecundity is a well-established fact. The selection process of men and women treated for infertility might bias the success rates of reproductive technology. Bias may also arise from frequency and timing of intercourse with respect to the day of ovulation. METHODS: Several datasets were collected and analysed. They concern normally fertile couples who used natural family planning methods and infertile couples treated by artificial insemination with husband or donor's spermatozoa. The effects of heterogeneity on the success rates of treatment cycles are described and solutions are proposed as to data collection and statistical analysis in this specific field. RESULTS: The decrease in the success rates along successive cycles of assisted reproduction is a consequence of heterogeneity. The probability of conception varies among women and among men. After a first success, the probability of another success is higher. After a failure, the probability of success is lower. The most specialised centres treat the less fecund couples. There is a negative correlation between men and women's fertility in case of oligo/azoospermia. The fecund window cannot be correctly located by calendar calculations, but more appropriately by assessment of cervical mucus at the vulva. The variability of this location is wide. The decrease in the success rate with men and women's age results from a complex mixture of an increase in the proportion of sterile patients and a decrease in fecund patients' fecundity. CONCLUSION: Care should be taken to limit the bias due to patient selection and specific statistical methods should be used to allow for the progressive selection of patients during fertility studies and for the variability of the frequency and the timing of intercourse or insemination relative to ovulation.

Data Interpretation, Statistical↗