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Antithyroid antibodies do not affect pregnancy outcome in women undergoing assisted reproduction.

The purpose of this study was to determine the association of antibodies to thyroglobulin and thyroid peroxidase and pregnancy outcome in women undergoing assisted reproductive techniques. The study included three centres and retrospectively evaluated patient sera for antithyroid antibodies, then related the results to pregnancy outcome. Enzyme-linked immunosorbant assays for thyroglobulin and thyroid peroxidase antibodies were performed using two different commercially available kits. Controls included 200 healthy women of reproductive age. Women (n = 873) who were undergoing assisted reproductive techniques for pelvic adhesions, endometriosis, ovarian dysfunction, or unexplained/other were included. All women utilized a standard regimen of gonadotrophin releasing hormone agonist down-regulation followed by ovulation induction. Embryos were cultured for 3 days, at which time embryo transfer occurred. Statistical analysis utilized the two-tailed Fisher's exact test. Antithyroid antibodies were positive in 143 of 873 (16.4%) women undergoing assisted reproductive techniques while 29 of 200 (14.5%) normal controls were positive (not significant). Deliveries were achieved in 396 of 730 (54.2%) of women who had no thyroid antibodies versus 78 of 143 (54.5%) of women who had thyroid antibodies (not significant). No difference in biochemical pregnancies (not significant) or clinical pregnancy losses (not significant) were detected. Antithyroid antibodies were found no more frequently in women undergoing assisted reproductive techniques than in normal controls. There were no differences in pregnancy outcome based on antithyroid antibody positivity in women undergoing assisted reproductive techniques. These data do not support the testing or treatment for antithyroid antibodies of women undergoing assisted reproductive techniques.

Autoantibodies↗

Evolving patterns of iatrogenic multifetal pregnancy generation: implications for aggressiveness of infertility treatments.

OBJECTIVE: Our purpose was to assess the changes in multifetal pregnancy generation as a function of utilization of ovulation stimulation and assisted reproductive techniques and to document the relative control of hyperstimulation between the methods. STUDY DESIGN: The methods of infertility treatment, number of fetuses, and outcomes of 220 patients referred for multifetal pregnancy reduction were compared over three time periods (1986 to 1989, 1991 to 1992, and 1992 to 1993). Clomiphene, human menopausal gonadotropin, and ovulation stimulation with urofollitropin were compared against gamete intrafallopian transfer, zygote intrafallopian transfer, and in vitro fertilization (assisted reproductive techniques). RESULTS: The proportion of multifetal pregnancies generated by assisted reproductive techniques has steadily risen from 26% in the first two time periods to nearly half in the last 2 years. However, the number and proportion of quintuplet and greater pregnancies from assisted reproductive techniques have steadily fallen while for ovulation stimulation the proportion has remained about one third. CONCLUSION: Despite considerably increased use and proportionate generation of triplet and quadruplet pregnancies, the incidence of quintuplets has fallen for assisted reproductive techniques while there has been no improvement for ovulation stimulation. Continued, greater vigilance, particularly in the use of human menopausal gonadotropin and urofollitropin, must be emphasized.

Clomiphene↗

Vibratory stimulation and rectal probe electroejaculation as therapy for patients with spinal cord injury: semen parameters and pregnancy rates.

PURPOSE: The conception rate of patients with spinal cord injuries following penile vibratory stimulation and rectal probe electroejaculation in conjunction with self-insemination, intrauterine insemination or assisted reproductive technique is poorly documented. We reviewed our success rates with penile vibratory stimulation and rectal probe electroejaculation, and the pregnancy rates achieved with self-insemination, intrauterine insemination and assisted reproductive techniques. MATERIALS AND METHODS: A total of 78 consecutive patients with spinal cord injuries had a complete neurological examination and was treated initially with penile vibratory stimulation. If unsuccessful, rectal probe electroejaculation was performed to obtain an ejaculate. The ejaculate was then used with self-insemination, intrauterine insemination or assisted reproductive techniques and pregnancies were monitored. RESULTS: Vibratory stimulation was successful in 20 of 37 patients (54%) with a cervical lesion, 14 of 26 (54%) with a lesion at or above T10 and none of 15 when the lesion was below T10. All patients except 2 who elected followup rectal probe electroejaculation had antegrade or retrograde ejaculate. Six patients (7.7%) with extremely poor semen quality were not candidates for assisted fertilization. Of 27 couples who attempted conception 17 were successful (5 self-insemination, 5 intrauterine insemination and 7 assisted reproductive techniques). CONCLUSIONS: Penile vibratory stimulation should be used as first line therapy in patients with lesions above T10 while rectal probe electroejaculation should be considered as a second option. Motivated patients can achieve success with self-insemination, intrauterine insemination and assisted reproductive techniques.

Adult↗

Perinatal and neonatal outcomes in multiple gestations: assisted reproduction versus spontaneous conception.

OBJECTIVE: Our purpose was to test the hypothesis that multiple pregnancies resulting from assisted reproductive therapy have a better outcome than those resulting from spontaneous conception. STUDY DESIGN: This was a retrospective cohort study. Cases came from pregnancies from assisted reproductive techniques. Controls were identified from spontaneous multiple pregnancies delivered in the same time period. Matching was done for maternal age, parity, fetal number, and presence of maternal medical problems. A total of 72 cases (56 twins and 16 triplets) and 124 controls (108 twins and 16 triplets) were studied. The primary outcome was perinatal mortality. Secondary outcomes were preterm delivery, birth weight, maternal complications, neonatal morbidity, and length of hospitalization. RESULTS: Perinatal mortality is significantly increased in spontaneous twin gestations compared with twins resulting from assisted reproductive techniques (24 vs 2, P =.003). No difference is seen in the perinatal mortality in triplets. Mean gestational age at diagnosis was lower for twins and triplets resulting from assisted reproductive techniques (9.4 vs 13.3; P <.001 and 8.8 vs 15. 8; P <.001, respectively). Rate of cerclage and number of prenatal visits was higher for triplets in the assisted reproductive techniques group (P =.05 and.02, respectively). Mean gestational age at delivery, birth weight, rate of preterm labor, preterm premature rupture of membranes, pregnancy-induced hypertension, and incidence of gestational diabetes were not significantly different between the groups. No significant differences in neonatal morbidity were detected. CONCLUSIONS: Assisted reproductive techniques-associated twins have lower perinatal mortality than spontaneously conceived twins. Perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by assisted reproductive techniques, even with closer surveillance and earlier gestational age at diagnosis in this group. Differences may be due to a higher frequency of monochorionic placentation in the spontaneously conceived group.

Adult↗

Transcervical artificial insemination in the cat.

Many studies have reported new reproductive techniques for reproduction in endangered non-domestic felids. Artificial insemination is an important tool for developing breeding programs. This manuscript reviews recent progress in feline artificial insemination, with particular emphasis on intrauterine sperm deposition. Intrauterine insemination of felids results in higher fertilization rates than intravaginal insemination, despite insemination with fewer sperm. Although surgical insemination was utilized historically, there are some reports of catheterization of the cervix of the queen. Recently, a new technique and catheter were proposed for transcervical insemination of fresh or frozen-thawed semen.

Animals↗

Successful pregnancy by transmyometrial and transtubal embryo transfer after IVF in a patient with congenital cervical atresia who underwent uterovaginal canalization during Caesarean section: case report.

Successful pregnancy in a patient with congenital cervical atresia is a great challenge for assisted reproductive techniques and reproductive medicine. We report a case of successful pregnancy by transmyometrial and transtubal embryo transfer simultaneously after in-vitro fertilization (IVF) in a 33 year-old patient with congenital cervical atresia diagnosed at the age of 18 years. The patient had experienced cyclic abdominal pain and amenorrhoea since she was 13 years old. She had had two unsuccessful attempts to create a new uterovaginal canal in another hospital. At the age of 32 years, she was referred to our unit and had a successful pregnancy after transmyometrial and transtubal embryo transfer. Caesarean section was performed at 36 weeks gestation due to progressive pre-eclampsia and gestational diabetes. A healthy male baby weighing 2812 g was safely delivered. Uterovaginal canalization with amniotic membrane for the covering of the neo-endocervical wall was performed during Caesarean section. Normal menstrual outflow and symptomatic relief have continued for 5 months after the operation. To the best of our knowledge, this is the first reported case of successful pregnancy by transmyometrial and transtubal embryo transfer as well as uterovaginal canalization performed during Caesarean section in a patient with congenital cervical atresia.

Amnion↗

First trimester biochemical screening for Down's syndrome in singleton pregnancies conceived by assisted reproduction.

BACKGROUND: Serum biochemical markers [free betahCG (fbetahCG); pregnancy-associated plasma protein-A (PAPP-A)] used in first trimester Down's syndrome screening have not been fully investigated in pregnancies achieved by assisted reproduction techniques. We present data on pregnancies conceived by all types of assisted reproduction techniques, including pregnancies following ovum donation (OD) and a large sample by ICSI. METHODS: First trimester Down's syndrome screening was performed in 1054 normal singleton pregnancies: natural conception (n = 498), ovulation induction (OS, n = 97), IVF (n = 47), ICSI (n = 222) and OD (n = 190). RESULTS: No differences in maternal levels of fbetahCG and PAPP-A, measured by the Kryptor system, appeared between naturally conceived pregnancies (n = 498) and those obtained with assisted reproduction techniques (n = 556). Several differences were apparent when comparing fbetahCG levels between different technologies but PAPP-A levels only differed between OS and IVF pregnancies (P < 0.05). In a further small study, no differences were observed using frozen embryos (n = 37), preimplantation genetic diagnosis (n = 53) or sperm from testicular biopsy (n = 21). CONCLUSIONS: Data accumulated so far suggest that first trimester biochemical markers either do not need any adjustments (e.g. in pregnancies obtained after OS and ICSI), or have very little impact (e.g. IVF pregnancies) or no impact (e.g. OD pregnancies) on the false positive rates.

Biomarkers↗

Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility.

OBJECTIVE: To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Prospective study. SETTINGS: Infertility clinic at a tertiary care academic institution. PATIENT(S): Ninety-two infertile men with normal female partners. Sixteen fertile donors served as the control group. INTERVENTION(S): Standard semen analysis and assessment of levels of seminal oxidative stress. Assisted reproductive techniques in 33 of the 92 patients (IUI [n = 19], IVF [n = 10], and intracytoplasmic sperm injection [n = 4]). MAIN OUTCOME MEASURE(S): Sperm DNA damage by sperm chromatin structure assay. Results were expressed as DNA fragmentation index. RESULT(S): Patients were classified as having either idiopathic (n = 23) or male factor infertility (n = 69). Patients with idiopathic and male factor infertility had significantly higher DNA fragmentation index and oxidative stress compared with the case of fertile donors. A clinical pregnancy was achieved in 9 (27%) of 33 patients with assisted reproductive techniques. Significantly higher DNA fragmentation index and oxidative stress were found in men who failed to initiate a pregnancy after assisted reproductive techniques (n = 24), compared with the cases of those who succeeded and of the fertile donors. DNA fragmentation index was correlated positively with oxidative stress (r = 0.27), and negatively with fertilization (r = -0.70) and embryo quality (r = -0.70). CONCLUSION(S): Sperm DNA damage is significantly increased in men with idiopathic and male factor infertility and in men who failed to initiate a pregnancy after assisted reproductive techniques. Such an increase may be related to high levels of seminal oxidative stress.

Adult↗

Implications of cloning technique for reproductive medicine.

The birth of Dolly following the transfer of mammary gland nuclei into enucleated eggs established cloning as a feasible technique in mammals, but the moral implications and high incidence of developmental abnormalities associated with cloning have induced the majority of countries to legislate against its use with human gametes. Because of such negative connotations, restrictive political reactions could jeopardize the therapeutic and scientific promise that certain types of cloning may present. For example, in addition to its proposed use as a way of generating stem cells, the basic technique of nuclear transplantation has proven useful in other ways, including its application to immature eggs as a new approach to the prevention of the aneuploidy common in older women, and for some recent advances in preimplantation genetic diagnosis. Thus, while attempts at reproductive cloning in man would seem premature and even dangerous at present, this field will require rational rather than emotional reactions as a basis for legislation if the therapeutic promise of stem cell research and the experimental potential of nuclear transplantation techniques are to be fully realized.

Cloning, Organism↗

Investigation of fertilizing capacity of cryopreserved spermatozoa from patients with cancer.

PURPOSE: There are few published reports concerning fertilization and pregnancy outcomes achieved with cryopreserved spermatozoa from cancer patients. Controversy exists regarding the value of sperm banking for these patients before therapy, whether the spermatozoa are viable after long-term storage and whether they can fertilize the ovum. We assess fertilization and pregnancy outcomes achieved with cryopreserved spermatozoa from cancer patients using assisted reproductive techniques. MATERIALS AND METHODS: We studied 10 cancer patients who transferred cryopreserved semen specimens from our sperm bank to outside in vitro fertilization programs for assisted reproductive technique. Of these patients 5 had Hodgkin's disease, 2 testicular cancer, 1 leukemia and 2 prostate cancer. The length of specimen storage ranged from 14 to 135 months (median 49, interquartile range 24 and 82). RESULTS: The median pre-freeze motility was 44% (interquartile range 36 and 55%) and the median total sperm count was 31.1 x 10(6) (interquartile range 6.3 and 53.9 x 10(6)). At 24 hours after banking the median post-thaw motility was 11% (interquartile range 6 and 35%) and the median total sperm count was 6.6 x 10(6) (1.2 and 17.1 x 10(6)). A total of 18 cycles of assisted reproductive technique were performed among 10 couples with an overall pregnancy rate of 50% per couple, with 2 deliveries, 1 ongoing pregnancy and 2 miscarriages. The pregnancy rate per cycle of in vitro fertilization and intracytoplasmic sperm injection was 36.4% with an implantation rate of 13%. CONCLUSIONS: These results indicate that poor quality cryopreserved spermatozoa from cancer patients, irrespective of the length of storage, may provide successful results with the latest micromanipulative techniques such as intracytoplasmic sperm injection.

Adolescent↗

[Assisted reproduction technologies and the risk of fetal, chromosomal and genetic malformations].

BACKGROUND: Assisted reproduction techniques allowed thousands of otherwise infertile couples to attain pregnancy. As this technology moves into the mainstream of infertility treatment, it has become more critical to reassess its safety. OBJECTIVE: To review the birth outcome of patients undergoing conventional in-vitro fertilization and intracyto- plasmic sperm injection regarding fetal malformations, chromosomal and genetic abnormalities. METHODS: Selective review of the literature. RESULTS: Most of the published data is from observational studies and is not randomized or blinded. Unfortunately, most articles are inherently biased. Chromosomal and genetic abnormalities are increased probably only as a direct corollary to the underlying parental risk and not due to the technology itself. There is a slight increase in the congenital malformations rate, but inspection of these malformations reveal no clustering of any specific abnormality. CONCLUSIONS: Children born after assisted reproduction technologies have an increased risk of a major congenital malformation and chromosomal abnormalities compared with those born after natural conception. The risk is mainly due to paternal and maternal risk factors, which are more prevalent in couples who use assisted reproduction techniques for reproduction. Infertility-linked risk is highly probable for the observed findings. A technique-related risk, however, cannot be ruled out. Intracytoplasmic sperm injection appears to be a safe alternative for couples who otherwise would be unable to achieve pregnancy. The inherent risks associated with these genetically "at risk" couples mandate thorough evaluation and counseling before undertaking ICSI.

Congenital Abnormalities↗

Is there a possible correlation between chromosomal variants and spermatogenesis?

AIM: Heterochromatin polymorphism is considered a variant of a normal karyotype but is more frequent in infertile men. The aim of this study was to evaluate the correlation between heterochromatic variants and male infertility and to discuss the possible mechanisms of how heterochromatic polymorphism might affect spermatogenesis. METHODS: Cytogenetic analysis was undertaken in 210 infertile males who had been taken into assisted reproductive techniques and in 183 men with proven fertility. Additionally, C-banding was performed in men with heterochromatin polymorphism. Sperm fluorescence in situ hybridization (FISH) was applied in 54 men with normal karyotype presenting either normal or abnormal sperm parameters as well as in 8 men with heterochromatin polymorphism. The outcomes of assisted reproductive techniques were compared between infertile men with normal karyotype and men with heterochromatin polymorphism. RESULTS: The incidence of heterochromatin polymorphism was higher in infertile men. The most frequent chromosome involved in heterochromatin polymorphism was chromosome 9. Sperm FISH analysis revealed an increased rate of aneuploidy in men with heterochromatin polymorphism. Laboratory and clinical outcomes in assisted reproductive techniques were compromised in men with heterochromatin polymorphism. CONCLUSIONS: An increased rate of heterochromatin polymorphism in infertile males seems to be more than an incidental finding, and must not be considered as a normal variant. Polymorphic heterochromatin may have deleterious effects on the genetic constitution of spermatozoa. More attention must be directed to infertile men with heterochromatin polymorphism.

Adult↗

Multiple gestation as a marker of reproductive efficacy: learning from assisted reproductive technologies.

This study postulates that apart from the number of embryos transferred, women with multiple gestation represent a subgroup of highly fertile individuals, whose embryos implant with higher efficiency than women with single gestation. Furthermore, each embryo generated from these women has a higher chance of reaching full term. The objective of this study was to compare implantation rate with the outcome of pregnancy (up to week 20) in multiple gestations following assisted reproductive techniques. The study group comprised 162 women with multiple gestation after assisted reproduction, followed prospectively with at least three ultrasound examinations performed between weeks 5 and 20 after the last menstrual period. Control group A comprised 344 fertile women with spontaneous single pregnancy followed with transvaginal ultrasound. Control group B consisted of 317 infertile women conceiving with single gestation after assisted reproduction and followed prospectively as in the study group. Embryo implantation rate and spontaneous embryo/fetal reduction, either partial or total (abortion), were registered in each case. Overall implantation in women with multiple gestation was higher (54.6%) than in the corresponding controls (25.6%). Furthermore, spontaneous embryo/fetus reduction was similar in the study cases and in fertile women (12.6 and 10.8% respectively) and significantly smaller than in the control group B (20.8%). Women with high reproductive efficacy exposed to assisted reproductive techniques generate cohorts of good quality embryos, with a high chance of implantation and of reaching birth.

Abortion, Spontaneous↗

Experience with vasal sperm aspiration.

PURPOSE: We describe our experience with vasal aspiration of sperm in patients with azoospermia secondary to neurogenic anejaculation or obstruction of the vas deferens. MATERIALS AND METHODS: We performed 15 vasal sperm aspirations on 11 patients with neurogenic anejaculation or vasal obstruction. RESULTS: Adequate sperm was obtained from all 15 aspirations with an average sperm count of 42 x 10[6] (range 0.5 to 252 x 10[6]) and an average motility of 73.4% (range 16 to 100%). Aspirations were performed for use with assisted reproductive techniques in 12 cases and for cryopreservation alone in 3. Following assisted reproductive techniques 6 of the 12 aspirations (50%) resulted in pregnancy. CONCLUSIONS: Vasal aspiration of sperm should be considered when electroejaculation fails, is not available or is contraindicated. Although the overall sperm quality and pregnancy rate are higher with vasal aspiration and in vitro fertilization than electroejaculation and intrauterine insemination, vasal aspiration is a more technically demanding and costly approach to conception.

Adult↗

The genetics of male infertility.

PURPOSE: We provide an up-to-date summary of the genetic aspects of male infertility. MATERIALS AND METHODS: The literature on male infertility was extensively reviewed. RESULTS: Genetic defects are associated with a variety of clinical presentations by the infertile man ranging from gonadotropin-releasing hormone deficiency to spermatogenic failure to obstructive azoospermia. Microsurgery and micromanipulation of gametes make it possible for many of these men to father children. However, with each successive breakthrough in treatment of male infertility there is an increased risk of transmitting genetic abnormalities to the progeny. CONCLUSIONS: Transmission of genetic defects through assisted reproductive techniques can have serious long-term implications. Assisted reproductive techniques should not be initiated in men with a possible or known genetic cause of infertility without prior genetic counseling and risk assessment. Clinicians and researchers involved in reproductive medicine must recognize that, although these techniques have revolutionalized the treatment of male infertility, they have the risk of passing genetic abnormalities to the progeny. Therefore, researchers must proceed cautiously with development and application of assisted reproductive technologies to avoid creating future generations of genetically abnormal individuals. The first step in accomplishing this goal is through an increased understanding of the genetic basis of male reproductive failure.

Chromosome Aberrations↗

ART in recurrent miscarriage: preimplantation genetic diagnosis/screening or surrogacy?

Recently, assisted reproductive techniques have been used to prevent further miscarriages in women with recurrent miscarriage. One approach uses either screening or diagnosis of embryonic chromosomes prior to embryo replacement [preimplantation genetic screening (PGS)/preimplantation genetic diagnosis (PGD)]. The second approach involves surrogacy. However, PGS/PGD assumes that the embryo is chromosomally abnormal, and that the mother should receive a chromosomally normal embryo. Surrogacy assumes that the embryo is normal and that the maternal environment needs to be substituted. This article examines the place of both techniques in different types of recurrent miscarriage, and tries to give guidelines as to which technique is preferable depending on the likelihood of an embryonic chromosome aberration. In repeated fetal aneuploidy or in the older patient, PGS or PGD are preferable. However, with high numbers of miscarriages, or in autoimmune pregnancy loss, surrogacy is preferable. In the light of recent work, it is uncertain which treatment mode is indicated in balanced parental chromosome aberrations. In conclusion, both techniques have a place, but probably only in those patients with a poor prognosis in whom assisted reproductive techniques will be shown to improve the subsequent live birth rate above the spontaneous rate.

Abortion, Habitual↗