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PubMed2026

Intermediate FMR1 cytosine‒guanine‒guanine repeats do not impair assisted reproductive technology outcomes in a large real-world cohort.

RESEARCH QUESTION: Does the presence of moderately elevated FMR1 cytosine‒guanine‒guanine (CGG) repeat numbers (40-70 repeats), identified through routine pre-pregnancy screening, adversely affect assisted reproductive technology (ART) outcomes in a real-world population? DESIGN: Retrospective cohort study including 760 first ART cycles conducted between 2010 and 2021 at a university-affiliated centre. FMR1 CGG repeat testing was conducted independently of infertility evaluation. Patients were categorized by repeat status in both alleles using two thresholds: 40 or more repeats (primary analysis) and 34 or more repeats (secondary analysis). Ovarian reserve markers, stimulation characteristics, oocyte yield, embryologic outcomes, positive beta-HCG and live birth rates were compared across groups. RESULTS: Among 760 patients, 669 (88%) had no allele of 40 or more repeats, 85 (11%) had one allele of 40 or more repeats and six (0.8%) had two alleles of 40 or more repats. The maximum observed repeat length was 71. Baseline demographics and ovarian reserve markers were similar between groups. No differences were observed in ovarian response, oocyte yield, fertilization or embryo development by FMR1 repeat category. Pregnancy and live birth rates were comparable between controls and patients with one expanded allele. Although elevated pregnancy and live birth rates were observed in patients with two expanded alleles, this subgroup was small, limiting interpretation. Analyses using the 34 or more repeat threshold yielded similar findings. CONCLUSIONS: Moderately elevated FMR1 CGG repeat numbers are not associated with impaired ART outcomes. Standard ART protocols remain appropriate, and FMR1 repeat length alone should not guide treatment modification in the absence of clinical ovarian insufficiency.

Humans↗
PubMed2006

Religion, infertility and assisted reproductive technology.

This chapter describes religion in general before discussing the centrality of its concern for family formation. In light of this, the impact of infertility on religious people is considered. Recognizing religion's cautiously positive attitude towards assisted reproductive technology (ART) as a potential ally in the project of family formation and the relief of infertility, two areas that have caused concern for the religions are discussed: perceived threats to marriage and the sanctity of the human embryo. Throughout the chapter, illustrations are drawn from particular religions, including Christianity, Judaism, Islam, Hinduism and Buddhism. There are striking similarities in their concerns and in the range of their responses to ART. Ways in which medical personnel should take into account the religious dimensions of the experience of infertility in their care for patients are suggested.

Female↗
PubMed1995

Ethical issues related to the new reproductive technologies.

Society's attitudes about the importance of genetic affiliations, both within and outside the family structure, as well as its attitudes about the appropriate limits on eugenic practices, strongly influence how physicians and researchers approach ethical problems related to reproduction technology. Scientific advances require us constantly to reassess ethical values, as well as the effect of technology on ethical values, and vice versa. Physicians' personal ethics, as well as those of their colleagues, are an integral and important part of the physician-patient relationship, which is the foundation of sound clinical ethics.

Commodification↗
PubMed1999

Assisted reproduction technology for patients with congenital bilateral absence of vas deferens.

PURPOSE: We investigate the frequency of cystic fibrosis transmembrane conductance regulator gene mutations in Japanese patients with congenital bilateral absence of the vas deferens, and assess treatment outcomes of assisted reproduction interventions. MATERIALS AND METHODS: In 10 Japanese patients with bilateral congenital absence of the vas deferens genetic analysis was performed for known frequent mutations of the cystic fibrosis transmembrane conductance regulator gene using polymerase chain reaction amplification followed by dot-blot hybridization with the allele-specific oligonucleotide probes and direct sequencing. Intracytoplasmic sperm injection using spermatozoa retrieved from the testes was performed in 7 of the couples. RESULTS: No known mutations of the gene were detected in the patients. However, analysis of the polythymidine tract polymorphism in intron 8 revealed 30% allele frequency of 5T. Pregnancy was achieved in 7 cycles of intracytoplasmic sperm injection using spermatozoa retrieved from the testes. CONCLUSION: The 5T variant in intron 8 polythymidine tract was identified with high allelic frequency in Japanese patients with congenital bilateral absence of the vas deferens, suggesting that the disease in Japan is also partially caused by this particular mutation of the cystic fibrosis transmembrane conductance regulator gene. Modern assisted reproduction technology offers an important option for patients with congenital bilateral absence of the vas deferens.

Adult↗
PubMed2005

Prospective, randomized trial comparing cetrorelix acetate and ganirelix acetate in a programmed, flexible protocol for premature luteinizing hormone surge prevention in assisted reproductive technologies.

OBJECTIVE: To compare the safety and efficacy of single-dose cetrorelix acetate (3 mg) and daily ganirelix acetate (0.25 mg) in the inhibition of premature LH surge in women undergoing cycle-programmed ovarian stimulation before Assisted Reproductive Technology (ART). DESIGN: Prospective, open-label, randomized, comparative study. SETTING: Sixteen ART centers in the United States. PATIENT(S): One hundred eighty-five infertile patients undergoing ART. INTERVENTION(S): Single injection of cetrorelix (3 mg SC) or daily dose of ganirelix (0.25 mg SC) was administered when the lead follicle was > or =14 mm. Daily cetrorelix (0.25 mg) was administered if the criteria for hCG administration were not met 4 days after receiving 3 mg of cetrorelix. MAIN OUTCOME MEASURE(S): Percentage of patients who did not have a premature LH surge, defined as LH <10 IU/L on the day of hCG administration. The IVF and embryo transfer (ET) outcomes were assessed. RESULT(S): No patient in either treatment group had a premature LH surge. There were no statistically significant differences between treatments for any IVF/intracytoplasmic sperm injection (ICSI) or ET outcomes, including pregnancy rate (PR). However, cetrorelix required significantly fewer injections than ganirelix. Similar safety profiles were observed. CONCLUSION(S): Cetrorelix and ganirelix effectively prevented LH surges in oral contraceptive (OC) pill-programmed, flexible protocols, with similar safety profiles and PRs; however, cetrorelix required significantly fewer injections, increasing patient convenience.

Adult↗
PubMed2001

Impact of a cryopreservation program on the multiple pregnancy rate associated with assisted reproductive technologies.

OBJECTIVE: To determine the impact of a cryopreservation program on pregnancy rates and multiple-pregnancy rates in ART cycles. DESIGN: Retrospective study. SETTING: University teaching hospital. PATIENT(S): Women who underwent stimulation for in vitro fertilization at the Jones Institute for Reproductive Medicine between October 1987 and June 1999. INTERVENTION(S): Analysis of pregnancy and multiple-pregnancy rates based on the number of embryos transferred. MAIN OUTCOME MEASURE(S): Implantation; pregnancy and multiple-pregnancy rates. RESULT(S): Pregnancy rates per transfer increased from 9% when one embryo was transferred to 20% with two embryos, 35% with three embryos, 40% with four embryos, and 41% with five embryos. The rate of twin pregnancies increased to 21% with two embryos, 23% with three embryos, 21% with four embryos, and 22% with five embryos. The triplet pregnancy rates were 8% with three embryos, 9% with four embryos, and 2% with five embryos. A theoretical model limiting the number of embryos transferred to two with cryopreservation and subsequent transfer yields a cumulative pregnancy rate of 77%, a twin rate of less than 20%, and no triplet or higher-order pregnancies. CONCLUSION(S): The use of a cryopreservation program can help maximize pregnancy rates while minimizing multiple-pregnancy rates. Cryopreservation should be considered in all assisted reproductive technology cycles.

Adult↗
PubMed2001

Quality of infertility care in poor-resource areas and the introduction of new reproductive technologies.

The quality of infertility care is dependent upon adequate material resources and the appropriate use of it. In addition, a mutual understanding between physicians and patients is necessary. These imperatives are more salient in the era of the new reproductive technologies. However, in poor-resource areas these imperatives are insufficiently met. Moreover, in developing countries the negative consequences of childlessness are much stronger than in Western societies. Until recently, the problem of infertility in Third World countries has received little public attention. A plea is made for a stronger policy interest in Third World infertility care. In this it is important to focus on prevention, appropriate diagnosis and treatment at primary and secondary health-care level and to take the existing cultural beliefs into account.

Developing Countries↗
PubMed2004

Do monochorionic dizygotic twins increase after pregnancy by assisted reproductive technology?

Although monochorionic (MC) dizygotic twins (DZT) are extremely rare in natural pregnancy, six pairs of such twins have successively been reported in a recent short period. All six cases of MC DZT were the products of pregnancy by assisted reproductive technology (ART). In this overview, we summarize these six cases and discuss possible mechanisms of this twinning and clinical implications of confined blood cell chimerism (CBC). The placental MC membrane was diagnosed ultrasonographically in all cases and pathologically in four. The presence of CBC was confirmed in four cases by haplotyping at polymorphic marker loci in peripheral blood leukocytes, karyotyping of lymphocytes and skin fibroblasts, and/or ABO blood group typing. As CBC is attributable to placental vessel anastomosis between DZT, it may become a risk factor for twin-twin transfusion syndrome (TTTS), mortality, and for other complications in twins. MC DZT may produce psychological trauma, especially in a girl/woman when she grows up and is known to be chimeric for a male karyotype and vice versa, although genital organs are generally normal--unlike freemartin in cattle. In addition, CBC in twins may mislead physicians when genotyping for a disease-susceptibility test is performed in medical practice in the near future. Blood group chimera may also cause confusion if a blood transfusion is necessary. Therefore, sufficient informed consent prior to ART and genetic counseling before/after birth are absolutely necessary for improved quality of life. It is most likely that all six cases are the consequence of fusion between two outer cell masses from two zygotes. The ART used in the six MC DZT included in vitro fertilization-embryonic transfer (IVF-ET) into the uterus, FSH-induced superovulation followed by intrauterine insemination, and/or intracytoplasmic sperm injection (ICSI). The use of an ovulation-inducing agent and implantation of several fertilized eggs at close sites are probably the events common among these cases. Assisted hatching, simultaneous ET, the use of eggs that have developed to the blastcyst stage, and cell culture procedures that lead to changes of the nature of cell surface, all may increase the chance of a cell fusion. This "chance hypothesis" can simply explain why MC DZT are very rare in natural pregnancy. Large-scale research on the prevalence of ART-associated MC DZT and long-term follow-up of the twins are essential.

Cell Fusion↗
PubMed1998

Optimizing pure line breeding strategies utilizing reproductive technologies.

The development of new reproductive techniques has had a great effect on schemes for dairy cattle improvement; AI resulted in progeny-testing schemes, and, more recently, multiple ovulation and embryo transfer has resulted in nucleus breeding schemes. In traditional breeding schemes, the use of multiple ovulation and embryo transfer resulted in only small increases of genetic gains because the selection intensity of bull dams was already high, but the selection intensity of cows in nucleus breeding schemes increased considerably. This increase makes nucleus schemes very competitive, especially when in vitro maturation and fertilization is used to increase female reproductive rates further. The increased genetic gain results in the selection of young females (i.e., optimal generation intervals are shortened). The combined effect of multiple ovulation and embryo transfer and shorter generation intervals increases the rate of gain by approximately 15% but also increases the rate of inbreeding and variances of the selection response (i.e., the risk of the breeding scheme) by about 80%. Recently, selection methods have been developed to reduce the rates of inbreeding or the variance of the selection response in breeding schemes. A scheme that maximized the selection differential while constraining the rate of inbreeding yielded about 30 to 60% more selection response than selection for BLUP estimated breeding value at the same rate of inbreeding. For the future, the combination of juvenile predictors of genetic merit (e.g., DNA markers) and techniques that further increase female reproductive rates seem very promising methods to increase the rates of genetic gain. As an example, the genetic gain of an optimized hybrid nucleus scheme could be increased 24% by the combined use of juvenile predictors and in vitro maturation and fertilization. Fertilization of fetal embryos was predicted to increase rates of gain by up to 18%.

Animals↗
PubMed2003

Assisted reproductive technologies and the pitfalls of unregulated biomedical innovation.

This Article suggests that the time has come to reconsider the safety and effectiveness of fertility drugs in order to combat some of the continuing problems arising from the overly aggressive use of assisted reproductive technologies, especially the health hazards associated with multifetal pregnancies. After critically assessing the arguments made by some commentators about the power of malpractice law to curb any abuses of fertility clinics and specialists, the Article concludes that the Food and Drug Administration should consider restricting or withdrawing pharmaceutical products used to induce ovulation. Although such a drastic move would not prevent the continued use of in vitro fertilization and other advanced fertility treatments, it would dramatically reduce the frequency of multifetal pregnancies, and it should not run afoul of any constitutional protections of procreative liberty.

Embryo Transfer↗
PubMed2003

Assisted reproductive technology for men and women infected with human immunodeficiency virus type 1.

In 2001, the World Health Organization reported 4.3 million new human immunodeficiency virus (HIV) infections in adults globally, 41% of which were in women. During the year 2000, 27% of newly diagnosed HIV infections in the United States occurred in women. In developed countries, the perception of HIV infection has changed from an acute, lethal infection to a chronic illness; the introduction of highly active antiretroviral therapy has decreased morbidity and mortality, and new drug therapies have dramatically decreased perinatal transmission. In view of these advances, some HIV-infected individuals are considering reproduction. Following the lead of organizations in other developed countries, the American College of Obstetricians and Gynecologists has recently endorsed the use of reproductive technology in HIV-infected patients. Which patients should be offered assisted reproduction and what the optimal methods are of decreasing heterosexual and perinatal HIV transmission must be determined.

Female↗
PubMed2004

Serum antimüllerian hormone/müllerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B, or estradiol.

OBJECTIVE: To test the hypothesis that the concentration of early follicular phase serum antimullerian hormone (AMH) or mullerian-inhibiting substance (MIS) is a useful marker of ovarian response and assisted reproductive technology (ART) outcome. DESIGN: Retrospective analysis of day 3 serum samples drawn before treatment. SETTING: Private ART program. PATIENT(S): One hundred nine consecutive serum samples from women younger than 42 years of age who were undergoing ovulation induction for IVF. INTERVENTION(S): Follicular aspiration for IVF after ovarian stimulation with FSH in a down-regulated cycle using GnRH-a treatment. MAIN OUTCOME MEASURE(S): Correlations between day 3 serum AMH/MIS, E2, FSH, inhibin B levels, and IVF outcome (i.e., number of retrieved mature oocytes, number and quality of embryos obtained, ongoing clinical pregnancy rates). Multivariate regression analysis on categorical data was performed to describe a predictive model of clinical pregnancy outcome. RESULT(S): Mean serum AMH/MIS value for clinical pregnancy (n = 38) was 2.4 ng/mL, in comparison to 1.1 ng/mL for those who did not become pregnant (n = 71). No differences were noted in mean values for day 3 FSH, inhibin B, or E2 between groups. Multivariate regression analysis demonstrated that day 3 serum AMH/MIS had the greatest independent contribution in predicting pregnancy outcomes. CONCLUSION(S): These data demonstrate a strong association between day 3 serum AMH/MIS level and IVF outcome in women younger than 42 years of age. Higher AMH/MIS concentrations are associated with a greater number of mature oocytes, a greater number of embryos, and ultimately a higher clinical pregnancy rate. Furthermore, AMH/MIS may offer greater prognostic value than other currently available serum markers of ART outcome.

Adult↗
PubMed2006

The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region.

BACKGROUND: Genomic imprinting refers to an epigenetic marking resulting in monoallelic gene expression and has a critical role in fetal development. Various imprinting diseases have recently been reported in humans and animals born after the use of assisted reproductive technology (ART). All the epimutations implicated involve a loss of methylation of the maternal allele (demethylation of KvDMR1/KCNQ1OT1 in Beckwith-Wiedemann syndrome (BWS), demethylation of SNRPN in Angelman syndrome and demethylation of DMR2/IGF2R in large offspring syndrome), suggesting that ART impairs the acquisition or maintenance of methylation marks on maternal imprinted genes. However, it is unknown whether this epigenetic imprinting error is random or restricted to a specific imprinted domain. AIM: To analyse the methylation status of various imprinted genes (IGF2R gene at 6q26, PEG1/MEST at 7q32, KCNQ1OT1 and H19 at 11p15.5, and SNRPN at 15q11-13) in 40 patients with BWS showing a loss of methylation at KCNQ1OT1 (11 patients with BWS born after the use of ART and 29 patients with BWS conceived naturally). RESULTS: 3 of the 11 (27%) patients conceived using ART and 7 of the 29 (24%) patients conceived normally displayed an abnormal methylation at a locus other than KCNQ1OT1. CONCLUSIONS: Some patients with BWS show abnormal methylation at loci other than the 11p15 region, and the involvement of other loci is not restricted to patients with BWS born after ART was used. Moreover, the mosaic distribution of epimutations suggests that imprinting is lost after fertilisation owing to a failure to maintain methylation marks during pre-implantation development.

Autoantigens↗
PubMed2005

How effective is assisted reproduction technology? A model assessment.

BACKGROUND: All conceptions occurring after a treatment for infertility are usually attributed to the treatment. This is only true when only totally sterile couples are treated: subfecund couples may still conceive without treatment. METHODS: We used a computer simulation (Monte Carlo) model of reproduction, combining the monthly probability of conceiving, the risk of miscarriage and the probability of age dependent permanent sterility. After a delay (D) without conceiving, the couples are assumed to turn to assisted reproduction technology. The treatment increases the fecundability (monthly rate of conception) of subfecund couples and restores the fertility of some totally sterile couples. The overall effectiveness of the therapy is based on data (by age of women) for two attempts of IVF. The number of conceptions ending in a live birth with ART is compared to the number of conceptions after one or two additional years without ART. RESULTS: At 30 years of age, the crude effectiveness of ART, based on all conceptions after treatment, is double that observed without treatment (30% vs. 15%), and beyond 41 years of age, the number of conceptions with treatment is no higher than without treatment over two years of exposure to conception (15% for both at 41 years of age, 7% at 45 years of age). Shortening the delay (D) does not improve the total number of women conceiving and having a live birth unless we assume the couple try again to spontaneously conceive. CONCLUSIONS: The chances of conceiving spontaneously must not be ignored when defining an infertility treatment, especially in cases of unexplained infertility. Shortening the delay before using ART is not in itself a more efficient strategy.

Computer Simulation↗
PubMed2005

Effect of myomectomy on the outcome of assisted reproductive technologies.

OBJECTIVE: To evaluate the impact of myomectomy on in vitro fertilization-embryo transfer (IVF-ET) and oocyte donation cycle outcome. DESIGN: Retrospective case-controlled study of consecutive fresh IVF-ET and oocyte donation patients during a 2-year interval. SETTING: Private assisted reproductive technology (ART) center. PATIENT(S): Patients with submucosal leiomyomata resected hysteroscopically (group A: 15 oocyte donor recipients; group 1 = 31 IVF-ET patients) and those with intramural components or strictly intramural leiomyomata that distorted or impinged upon the endometrial cavity resected at laparotomy (group B = 26 oocyte donor recipients; group 2 = 29 IVF-ET patients). INTERVENTION(S): Precycle hysteroscopic or abdominal myomectomy and subsequent fresh IVF-ET or oocyte donation. MAIN OUTCOME MEASURE(S): Results of controlled ovarian hyperstimulation as well as ongoing pregnancy and implantation rates were evaluated in comparison with contemporaneous patient groups without such lesions (group C = 552 oocyte donor recipients; group 3: 896 IVF-ET patients). RESULT(S): As would be expected, the mean number and size of leiomyomata were significantly larger in patients who underwent abdominal myomectomy. However, neither ongoing pregnancy nor implantation rates were significantly different in comparison with controls among either oocyte donor recipients (group A: 86.7%, 57.8%; group B: 84.6%, 55.2%; group C 77%, 49.1%). The findings were similar for those undergoing IVF-ET in comparison with controls (group 1: 61%, 24%; group 2: 52%, 26%; group 3: 53%, 23%). CONCLUSION(S): Precycle resection of appropriately selected clinically significant leiomyomata results in IVF-ET or oocyte donation cycle outcomes that are similar to controls.

Adult↗
PubMed2003

Acute urinary retention after use of assisted reproductive technology. A report of 2 cases.

BACKGROUND: Urinary retention in women is an unusual occurrence. Various conditions can cause it, including surgery, childbirth, pelvic masses, procidentia, vulva hematoma, incarceration of a gravid uterus, urologic disease, neurogenic disease and psychiatric disorders. CASES: Two infertile women underwent assisted reproductive technology (ART) and luteal-phase support during which acute urinary retention occurred. The patients were evaluated by means of physical examination, urodynamic study and determination of serum progesterone levels. Bladder distention was found during luteal-phase support. Urodynamic studies revealed detrusor areflexia. Serial serum progesterone levels were > 100 ng/mL. CONCLUSION: Cases of acute urine retention during luteal-phase support are rarely reported. Urine retention should be considered in the differential diagnosis when abdominal pain occurs after patients undergo ART. Transient elevation of the progesterone level may be the cause of the acute urine retention.

Acute Disease↗
PubMed2005

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study.

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.

Abortion, Spontaneous↗
PubMed2003

Comparison of recombinant human luteinising hormone (r-hLH) and human menopausal gonadotropin (hMG) in assisted reproductive technology.

Follicle-stimulating hormone (FSH) and luteinising hormone (LH) act in concert in the stimulation of folliculogenesis and ovulation. However, high levels of LH promote follicular atresia and early miscarriage, and this has led to the concept of a 'therapeutic window' of LH for successful conception in assisted reproductive technology (ART) and ovulation induction. Until now, urinary-derived human menopausal gonadotropin (hMG) has been the only available source of exogenous LH activity. hMG preparations contain highly variable levels of LH, and are often augmented with human chorionic gonadotropin (hCG), which mimics LH activity. Accumulation of hCG bioactivity, however, may have detrimental effects on follicular development and oocyte quality. Recombinant human LH (r-hLH) (Luveris) is the only pure source of LH activity. r-hLH is well characterised and production is tightly controlled, resulting in a highly consistent product. Clinical studies in hypogonadotropic hypogonadal women have demonstrated the efficacy of r-hLH, 75 IU/day, together with r-hFSH, 150 IU/day, in promoting optimal follicular development, oestrogen secretion and endometrial thickness. r-hLH therefore provides the clinician with the opportunity for precise and consistent dosing within the therapeutic window for patients requiring exogenous LH, without the risk of LH overexposure that is associated with hCG.

Dose-Response Relationship, Drug↗