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[Obesity and assisted reproduction techniques].

Obesity was defined by a body mass index more than 30 kg/m2. Many risks were related to this pathology, and sometimes, menstrual disorders or infertility. In order to obtain an adequate response to ovarian stimulation during IVF cycles, higher doses of menotropins are necessary in the group of obese patients. The mechanism of this phenomenon is still unclear. Leptin is one of the main hypothesis, and could act on obesity and reproductive system simultaneously. The likelihood to have an ongoing pregnancy after IVF treatment is less in the group of obese patients because of the increased risk of miscarriage and obstetrical complications. Weight loss prior IVF remains the main advice in order to decrease the risks of the procedure and to treat successfully these patients.

Body Mass Index↗

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↗

Results in the United States with sperm microaspiration retrieval techniques and assisted reproductive technologies. The Sperm Microaspiration Retrieval Techniques Study Group.

Improved methods of urological microsurgery and of various assisted reproductive technologies have resulted in the ability to achieve pregnancies with sperm aspirated microsurgically from men with bilateral congenital absence of the vasa deferentia or with ductal obstructions that cannot be surgically reconstructed. A survey was conducted of the results of such procedures performed in the United States during approximately 2 years. Female partner ovarian stimulation was initiated in 219 instances at 22 centers. Of the 219 procedures 23 (11%) were terminated without attempting any form of gamete fertilization or insemination of the wife for various reasons (no sperm or too few sperm retrieved, poor to absent sperm motility or poor quality eggs). The etiology of azoospermia in the 219 procedures was congenital absence of the vasa deferentia in 115 cases (52%), other congenital conditions in 15 (7%), failed vasectomy reversal in 37 (17%), infection in 4 (2%), other conditions (mainly ejaculatory dysfunctions that did not respond to electroejaculation and complex ductal obstructions) in 26 (12%) and not specified in 22 (10%). When only patient sperm was used pregnancy was achieved in 12 of 115 wives (10%) of those men who had congenital absence of the vasa deferentia and in 0 to 14% of the wives of men whose azoospermia was caused by other conditions. Of the 219 menstrual cycles in which ovarian stimulation was initiated pregnancy occurred in 24 (11%) with patient sperm and in 9 (4%) with donor sperm. Of these 33 pregnancies a full-term, live delivery occurred in 17 (52%), while 8 (24%) were ongoing at the time of reporting, 2 (6%) miscarried, 3 (9%) were chemical pregnancies, 1 (3%) resulted in a stillborn child and the outcome was unknown in 2 (6%). This new therapy offers only a modest chance of pregnancy. However, it affords men with azoospermia the opportunity to achieve paternity with their own sperm when other therapies are not available or applicable.

Epididymis↗

Medically assisted reproduction in the presence of chronic viral diseases.

Teams practising medically assisted reproduction techniques try to avoid viruses as much as possible. Attitudes towards chronic carriers of viruses are rapidly changing, especially for human immunodeficiency virus (HIV) patients. We focus our attention on the legitimacy of systematic screening before assisted reproductive techniques and the need for specialized approaches including an adapted laboratory for viral hazards as well as the need for a multidisciplinary team. Specificities of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV) carriers and the hypothesis of a reduced fertility potential are discussed. Are male HIV carriers a new indication for assisted reproductive techniques in order to prevent virus transmission? It is largely proven that sperm gradient preparation techniques efficiently decrease viral loads and therefore have a protective effect on contamination risk during assisted reproductive techniques. Although a few thousand assisted reproductive technique cycles were performed in the world for this indication without contamination, it is still too early to demonstrate that this technology is fully safe. Two examples of contaminations during insemination are examined. Many questions remain unresolved, such as the lack of standardized techniques for semen preparation or virus detection or the relative merits of intrauterine insemination or ICSI to prevent HIV contamination during assisted reproductive techniques. The authors plead for well-structured, separate programmes of care linked to research objectives.

Acquired Immunodeficiency Syndrome↗

Italy enacts new law on medically assisted reproduction.

In 2004, the Italian Parliament enacted a law regulating medically assisted reproduction. Although the law recognizes as legal certain assisted reproduction techniques, several other procedures are implicitly or expressly banned: oocyte and sperm donation, using embryos for the scientific research purposes and reproductive cloning. In this article, I outline the new legal framework, pointing out some of the shortcomings of its provisions, such as the failure to define what an 'embryo' is, the contradictions between this law and the law on abortion, the opportunity for Italian couples to circumvent some of the prohibitions by resorting to 'reproductive tourism', and the central role that physicians play in the new legal framework.

Cryopreservation↗

Male infertility in spinal cord trauma.

Every year there are 10 thousand new cases of patients victimized by spinal cord trauma (SCT) in the United States and it is estimated that there are 7 thousand new cases in Brazil. Eighty percent of patients are fertile males. Infertility in this patient group is due to 3 main factors resulting from spinal cord lesions: erectile dysfunction, ejaculatory disorder and low sperm counts. Erectile dysfunction has been successfully treated with oral and injectable medications, use of vacuum devices and penile prosthesis implants. The technological improvement in penile vibratory stimulation devices (PVS) and rectal probe electro-ejaculation (RPE) has made such procedures safer and accessible to patients with ejaculatory dysfunction. Despite the normal number of spermatozoa found in semen of spinal cord-injured patients, their motility is abnormal. This change does not seem to be related to changes in scrotal thermal regulation, frequency of ejaculation or duration of spinal cord damage but to factors related to the seminal plasma. Despite the poor seminal quality, increasingly more men with SCT have become fathers through techniques ranging from simple homologous insemination to sophisticated assisted reproduction techniques such as intracytoplasmic sperm injection (ICSI).

Erectile Dysfunction↗

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↗

A woman's choice? On women, assisted reproduction and social coercion.

This paper critically discusses an argument that is sometimes pressed into service in the ethical debate about the use of assisted reproduction. The argument runs roughly as follows: we should prevent women from using assisted reproduction techniques, because women who want to use the technology have been socially coerced into desiring children--and indeed have thereby been harmed by the patriarchal society in which they live. I call this the argument from coercion. Having clarified this argument, I conclude that although it addresses important issues, it is highly problematic for the following reasons. First, if women are being coerced to desire to use AR, we should eradicate the coercive elements in pro-natalist ideology, not access to AR. Second, the argument seems to have the absurd implication that we should prevent all women, whether fertile or not, to try to have children. Third, it seems probable that women's welfare will be greater if we let well informed and decision-competent women decide for themselves whether they want to use AR.

Coercion↗

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↗

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↗

How to prevent 'half-bastard' progeny? or An alternative for three-parent babies: two-parent babies through transplantation of sperm mitochondria.

Body development and activity depend on the level of internal energy generation. Therefore, unaffected, optimally active mitochondria are indispensable in a healthy and vital body. A mutation in the DNA of the semi-autonomous mitochondria (mtDNA) may cause an inheritable insufficiency that is due to decreased energy generation needed for adequate development. Sperm mitochondria will not enter the egg cell during fusion of male and female gametocytes. Since women with mutated mtDNA will increasingly know and realize the effect of such mutation in their own body, they will more often ask for treatment to stop the effect of such inconvenient mutation in their progeny. Thus far, solutions for this problem were thought to be: (i) nucleus transplantation just after fertilization into a nucleus-free egg cell of a second healthy woman and later (ii) transplantation of healthy mitochondria from a second woman into the egg cell before fertilization. Although both transplantations create babies with three, instead of two-parents that have contributed to the genetic content, in case of the newer mitochondria transplantation technique the part of the second woman is somewhat more reduced, but still clearly present. Thus, assisted-reproduction techniques that mix egg cell mitochondria from two women may create not only 'three-parents' babies, but also fears for 'three-parents' babies, since this handling may create non-scientific problems, especially regarding emotional, ethical, religious and juridical aspects of life. Transplantation of healthy sperm mitochondria of the partner into the egg cell with insufficient mitochondria is thought to be the best solution for this problem, since it may create a 'two-parents' instead of a 'three-parents' baby. This only implies that at the moment of (successful) transplantation the biological dogma is broken that mitochondria are maternally inherited: the mitochondria of the maternal line of the woman will have been substituted by the mitochondria of the maternal line of the man.

Female↗

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↗

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↗

Perspectives: the possible influence of assisted reproductive technologies on transgenerational reproductive effects of environmental endocrine disruptors.

Demasculinization by environmental endocrine-disrupting chemicals (EDCs) is observed in many animal species but less evident in humans. Rodent studies with gestational exposure to either the fungicide vinclozolin or the insecticide methoxychlor demonstrate impaired male fertility with abnormal DNA methylation patterns in spermatozoa. Once established, these epigenetic changes may be permanent and thus paternally passed to subsequent generations. Conclusive evidence of a similar phenomenon in humans has not been established, but several observations bring up the possibility. Some, but not all, studies show an increase in male genital abnormalities after prenatal EDC exposure. Other studies demonstrate sperm abnormalities in males with EDC contact, although it is unclear as to whether this is due to prenatal or postnatal exposure. Although not examined in males with EDC exposure, one study shows gamete DNA methylation abnormalities in males with severe oligospermia. A subsequent study failed to corroborate these findings. The use of assisted reproductive techniques including intracytoplasmic sperm injection has removed natural selection barriers thus enabling reproduction in males that would otherwise be sterile. This review explores the hypothesis that prenatal EDC exposure results in transgenerational male reproductive abnormalities propagated by the use of assisted reproductive technologies.

Animals↗