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PubMed2006

Infertility, infertility treatment, and congenital malformations: Danish national birth cohort.

OBJECTIVES: To examine whether infertile couples (with a time to pregnancy of > 12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations. DESIGN: Longitudinal study. SETTING: Danish national birth cohort. PARTICIPANTS: Three groups of liveborn children and their mothers: 50,897 singletons and 1366 twins born of fertile couples (time to pregnancy < or = 12 months), 5764 singletons and 100 twins born of infertile couples who conceived naturally (time to pregnancy > 12 months), and 4588 singletons and 1690 twins born after infertility treatment. MAIN OUTCOME MEASURES: Prevalence of congenital malformations determined from hospital discharge diagnoses. RESULTS: Compared with singletons born of fertile couples, singletons born of infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations-hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born of infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins. CONCLUSIONS: Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination.

Cohort Studies↗
PubMed2000

Ethics and assisted reproduction.

In vitro fertilization and assisted reproductive technology have made great progress during the last 20 years. Genetic material donation, human embryo cryopreservation, selective embryo reduction, preimplantation genetic diagnosis and surrogacy are currently practiced in many countries. On the other hand, embryo research is practiced only in a small number of nations, whereas human cloning has thus far been universally condemned. The rapid evolution and progress of all these techniques of assisted reproduction has revealed certain ethical issues that have to be addressed.

Cloning, Organism↗
PubMed2005

Deaths of HIV-positive men in the context of assisted reproduction: five case studies from a single center.

Provision of reproductive services to individuals infected with HIV-1 is gaining popular acceptance and is generally endorsed by specialists in reproductive medicine. In the situation in which the male is HIV positive and the female partner is not infected, a large body of evidence has demonstrated that the use of assisted reproductive technology is effective for achieving pregnancy, while eliminating the risk of viral transmission to the mother and fetus. No reports have documented the well-being of the HIV-infected partners subsequent to seeking fertility services. In the current report, we document the cases of five HIV-positive men who died secondary to complications of HIV infection shortly after participating in the assisted reproduction program for HIV-1-serodiscordant couples at Columbia University. Three of these couples successfully achieved pregnancy and live birth, including one set of triplets, and one case of posthumous conception; the fourth case resulted in the cryopreservation of all embryos after the sudden death of the male before the time of embryo transfer; the fifth couple failed to conceive. None of the deaths, which occurred within a few months to 2 years from initial consultation, were related to infertility treatment. The demographic and social statuses of these patients were not different from the general population of men seeking assisted reproduction in our clinic. Regarding the HIV infection status of these cases, three patients had a longer duration of infection compared to the general population of men in our cohort, and one had a significantly lower CD4 cell count. All five men had stable HIV viral loads, and were determined by their primary care providers to be clinically healthy at the time of entry into the program for assisted reproduction. The untimely deaths of these patients underscores the importance of the thoughtful consideration of the complex issues involved in family planning for these individuals, including advanced directives for the use of cryopreserved gametes and embryos, and the social, emotional, and practical issues for the children and surviving partners subsequent to the death of the HIV-positive parent.

Adult↗
PubMed2005

Harming by conceiving: a review of misconceptions and a new analysis.

An objection often is raised against the use of reproductive technology to create "nontraditional families," as in ovum donation for postmenopausal women or postmortem artificial insemination. The objection states that conceiving children in such circumstances is harmful to them because of adverse features of these nontraditional families. A similar objection is raised when parents, through negligence or willful disregard of risks, create children with serious genetic diseases or other developmental handicaps. It is claimed that such reproduction harms the children who are created. In reply to this Harm to the Child Argument, it has been pointed out that the procreative acts that supposedly harm the child are the very acts that create the child. This reply has been developed into an argument that, in most of the types of cases under consideration, creating the child does not harm her. This reply, the No Harm Argument, has been stated in three main ways, and it is one of the most misunderstood arguments in bioethics. This paper examines the main rebuttals that have been made to the No Harm Argument and argues that none of them is successful.

Ethical Theory↗
PubMed2004

A survey of the practices and opinions of the domestic members of the American Society for Reproductive Medicine.

OBJECTIVE: To learn how the domestic members of the American Society for Reproductive Medicine (ASRM) use its services and to survey their opinions regarding clinical practices and research in reproductive medicine. DESIGN: A self-administered mail survey. SETTING: Members of a professional organization. SUBJECT(S): A total of 1,291 members responded. Of these, 80% were physicians, embryologists, or nurses. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographics, use of ASRM services, and opinions. RESULT(S): Eighty-five percent of the respondents provided some type of clinical care for individuals with fertility problems. Two thirds read the ASRM News, and more than half used ASRM Practice Committee statements, Ethics Committee opinions, and patient education materials. Eighty-three percent reported that they followed the Ethics Committee opinions. Whereas 78% did not support reproductive cloning, two thirds supported somatic cell nuclear transfer to produce stem cells for research. The majority opposed governmental regulation of assisted reproductive technologies. CONCLUSION(S): The domestic membership of the ASRM is diverse in terms of demographics, practices, and opinions. In addition, they find the services of the ASRM to be of value.

Attitude of Health Personnel↗
PubMed1995

Pregnancies after microsurgical correction of partial epididymal and vasal obstruction.

A group of 16 infertile patients suspected of having a partial epididymal obstruction on the basis of severe oligozoospermia, normal-sized testes and a normal serum follicle-stimulating hormone, underwent scrotal exploration. Evidence of partial obstruction of the epididymis was found in 13 cases and of the vas deferens in one case, and was supported by finding normal spermatogenesis on testicular biopsy. Vasoepididymostomy or vasovasostomy were performed, resulting in a significant improvement of semen analysis in 50% of cases and in six pregnancies in two patients. The diagnosis of partial epididymal obstruction should be considered when the above criteria are met. If pregnancies do not result when intracytoplasmic sperm injection (ICSI) is used with the ejaculated spermatozoa, a testicular biopsy followed by a microsurgical by-pass procedure should be considered whenever normal spermatogenesis is diagnosed. In all cases, the epididymal spermatozoa should be aspirated during the operation and either used immediately for insemination or stored frozen. The remarkable results of the new artificial reproduction technologies and in particular ICSI, question the indication for microsurgical correction in cases of partial epididymal obstruction.

Adult↗
PubMed2006

Maintenance of pregnancy in pigs with limited viable embryos.

Interest is increasing in assisted reproductive technologies in the pig involving embryo cryopreservation, cloning, and genetic modification. Although inherently inefficient and variable in their outcome, the successful application of these techniques in this species is confounded by unique mechanisms for pregnancy recognition and maintenance that require a minimum number of viable embryos during a critical window of time early in gestation. These mechanisms require both local and systemic interactions between conceptuses and the maternal reproductive axis. Here, we describe a method wherein cotransfer of parthenogenetic embryos with the capacity for limited development can be used to sustain the pregnancy of fewer than four viable conceptuses to term.

Animals↗
PubMed2006

Sperm DNA damage: importance in the era of assisted reproduction.

PURPOSE OF REVIEW: With the proliferation of assisted reproductive technologies, there is an increasing awareness of the importance of sperm DNA damage. With the recent advent of in-vitro fertilization/intracytoplasmic sperm injection, we are bypassing the normal natural selection barriers and potentially introducing sperm with damaged DNA. To date, these consequences are still largely unknown. RECENT FINDINGS: Infertile men possess substantially more DNA-damaged sperm than fertile men, and this DNA damage may adversely affect reproductive outcomes. There may be a threshold level of DNA damage beyond which embryo development and subsequent pregnancy are impaired. Protamine deficiency and the effect of reactive oxygen species have been implicated in the etiology of sperm DNA damage. Assays of DNA damage are being used clinically to quantify objectively the degree of DNA damage in the sperm of infertile men in the hope of identifying more accurate ways of gauging fertility potential. SUMMARY: There now exists clinical evidence to show that sperm DNA damage is detrimental to reproductive outcomes. Tests for DNA damage may provide better prognostic information and may allow for better decision-making than standard semen parameters when evaluating the infertile couple. The etiology of the DNA damage and the full extent of the damage on reproductive outcomes need further study.

Chromatin↗
PubMed2000

Avoiding multiple pregnancies in ART: consideration of new strategies.

To maximize pregnancy rates, physicians who perform IVF, often transfer multiple embryos, which increases the multiple birth risk. Multiple birth infants are at significant risk for a number of adverse outcomes including preterm delivery, low birth weight, congenital malformations, fetal and infant deaths and long term morbidity and disability among survivors. Since the ultimate goal for an IVF treatment is the birth of a healthy infant, an important issue for all kinds of assisted reproductive technologies (ART) must be the reduction or elimination of multiple pregnancies. In this article, different strategies to avoid multiple births in ART are discussed.

Female↗
PubMed2006

Acupuncture as adjunctive therapy in assisted reproduction: remaining uncertainties.

Two randomized trials provide suggestive evidence that acupuncture might be an effective adjunctive therapy in assisted reproductive technologies, leading to improved pregnancy rates. However, additional research addressing remaining scientific and methodologic issues is needed before routine use of acupuncture can be recommended.

Acupuncture↗
PubMed2000

Y-chromosome microdeletion and its effect on reproductive decisions in taiwanese patients presenting with nonobstructive azoospermia.

OBJECTIVES: To investigate the position, extent, and frequency of Y chromosome microdeletions in Taiwanese patients presenting with nonobstructive azoospermia, and to investigate the effect of microdeletions on reproductive decisions. METHODS: We studied 176 consecutive men with azoospermia in our urology clinic. Polymerase chain reaction tests were performed in 94 patients with nonobstructive azoospermia, and a series of 27 sequence-tagged sites (STSs) mapped within intervals 5 and 6 of Yq11 was selected for analysis. Clinical genetics counseling was provided to couples with microdeletions, and these couples made their own choices about further treatment modalities. RESULTS: Among 94 patients screened for microdeletion, 11 (11.7%) showed microdeletions of one or more STSs. One had a deletion confined to the azoospermia factor b (AZFb) region (encompassing the RBM gene). Two were found to have deletions of both the AZFb and AZFc regions. Eight patients had deletions in the AZFc region (encompassing the DAZ gene). Five had deletions distal to the DAZ gene family. One had multiple, noncontiguous deletions. In 8 patients with testicular histology available, a lack of genotype/phenotype correlation was noted. Of the 11 couples with deletions, 3 thought microdeletion was a serious defect and opted for an artificial insemination of donor or adoption, 5 chose intracytoplasmic sperm injection, and the other 3 decided to undergo treatment with Chinese medicinal herbs. CONCLUSIONS: The most commonly deleted region in the Taiwanese population is AZFc. The genes implicated in Taiwanese spermatogenesis defects are the DAZ and RBM gene families. Twenty-seven percent of couples with microdeletions deferred assisted reproductive technologies because of concern about their underlying genetic defects.

Adoption↗
PubMed1993

Resource allocation and the beginning of life.

Like many other countries, Australia is increasingly being forced to face the spiralling costs of health care. Population increases, an aging population, and the high cost of many items of modern medical equipment and of medical care generally, have all contributed to the pressure on health care resources. Within this climate of resource scarcity, more and more questions are being asked about the prioritization of items of health expenditure. The aim of this article is to consider the claim of reproductive technology, prenatal care, and prenatal diagnosis on health care resources and to evaluate the balance between treatments and preventative measures.

Australia↗
PubMed2003

New microinsemination techniques for laboratory animals.

Since the development of a reliable mouse intracytoplasmic sperm injection (ICSI) technique in 1995, microinsemination techniques have been widely applied in several laboratory species. As gametes and embryos have specific biological and biochemical features according to the species, technical improvements are necessary for successful microinsemination that subsequently leads to normal fetal development in several species. Recent advanced reproductive research involving genetic engineering often depends on microinsemination techniques that require a high degree of skill, and new human assisted reproductive technology (ART) requires experimental models using laboratory animals. The accumulation of technical improvements in these fields should accelerate the development of microinsemination techniques in mammals, including humans.

Animals↗
PubMed2001

Vascular endothelial growth factor, platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 in the follicular fluid of patients undergoing IVF.

BACKGROUND: The aim of our study was to measure concentrations of vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) CD31 and vascular cell adhesion molecules (VCAM-1) in the follicular fluid of women treated with assisted reproduction technology to determine whether these proteins might be outcome markers. METHODS: Follicular fluid was collected from 75 patients < or =40 years undergoing oocyte retrieval procedures at our tertiary hospital during 1997 and 1998: 50 with tubal disease, 12 with endometriosis, and 13 whose partners had been diagnosed with severe oligoasthenoteratozoospermia. This retrospective analysis considered age and information about treatment and outcome for all these women who had undergone fewer than three assisted reproduction attempts. RESULTS: Nineteen women became pregnant (defined by human chorionic gonadotrophin concentrations and embryonic cardiac activity 1 month after follicular aspiration); 56 did not. Women did not differ significantly in their follicular fluid concentrations of VEGF, sCD31 and VCAM-1 according to cause of infertility, or assisted reproduction outcome, or age. Follicular fluid concentrations of VEGF were significantly correlated with the number of gonadotrophin ampoules administered (P < 0.012), and follicular fluid concentrations of sVCAM-1 with the fertilization rate (P < 0.01). Follicular fluid concentrations of VEGF and sVCAM-1 were also correlated (P < 0.007). CONCLUSIONS: Our results do not suggest that VEGF, CD31, or sVCAM-1 in follicular fluid predict assisted reproduction outcome, especially among patients < or =40 years old. The correlation of a high fertilization rate and sVCAM-1 in follicular fluid suggests that sVCAM-1 might be a marker of fertilization.

Abortion, Spontaneous↗
PubMed2002

Potential importance of vitrification in reproductive medicine.

As early as 1985, ice-free cryopreservation of mouse embryos at -196 degrees C by vitrification was reported in an attempted alternative approach to cryostorage. Since then, vitrification techniques have entered more and more the mainstream of animal reproduction as an alternative cryopreservation method to traditional slow-cooling/rapid-thaw protocols. In addition, the last few years have seen a significant resurgence of interest in the potential benefits of vitrification protocols and techniques in human-assisted reproductive technologies. The radical strategy of vitrification results in the total elimination of ice crystal formation, both within the cells being vitrified (intracellular) and in the surrounding solution (extracellular). The protocols for vitrification are very simple. They allow cells and tissue to be placed directly into the cryoprotectant and then plunged directly into liquid nitrogen. To date, however, vitrification as a cryopreservation method has had very little practical impact on human-assisted reproduction, and human preimplantation embryo vitrification is still considered to be largely experimental. Besides the inconsistent survival rates that have been reported, another problem is the wide variety of different carriers and vessels that have been used for vitrification. Second, many different vitrification solutions have been formulated, which has not helped to focus efforts on perfecting a single approach. On the other hand, the reports of successfully completed pregnancies following vitrification at all preimplantation stages is encouraging for further research and clinical implementation. Clearly, however, attention needs to be paid to the inconsistent survival rates following vitrification.

Animals↗
PubMed1991

Male infertility: the focus shifts to sperm manipulation.

Few systemic approaches for treatment of the infertile male are available. Therefore, the focus has shifted to studies of sperm maturation in the female tract, tests of sperm function, and assisted reproduction. New methods of sperm evaluation allow a better determination of those samples that will and will not fertilize ova. These methods include the strict morphology examination, biochemical approaches such as evaluation of creatine kinase levels, and the hemizona assay. Computer assisted semen analysis has not yet proved important for diagnosis but has provided important research information. For example, the drug pentoxifylline significantly increases velocity and has also been shown to enhance in vitro fertilization. The term subfertile is extensively used in the literature but its clear definition and the prognosis for subfertile men have not been established. Approaches that may increase fertilization rates include reducing the gamete culture volume and removal of cumulus oophorus. Assisted reproductive technologies for patients with ejaculatory dysfunction have also been expanded. The use of improved semen processing techniques, advanced oocyte retrieval, and well-timed intrauterine insemination are enabling physicians to use decreasing numbers of viable sperm to achieve pregnancies.

Humans↗
PubMed2004

Aromatase inhibitors: possible future applications.

In premenopausal women ovaries are the major sites of estrogen production, while in postmenopausal women estrogen is produced by aromatization of ovarian and adrenal androgens in extragonadal sites, mostly in adipose tissue. Aromatase is a cytochrome P450 hemoprotein-containing enzyme complex that catalyzes the rate-limiting step in the conversion of androstenedione and testosterone to estrone and estradiol (E2). Aromatase inhibitors (AIs) have been developed primarily for use in either natural or surgical postmenopausal patients. In premenopausal women, the ovary can overcome the estrogen blockade by reflex increments of luteinizing hormone (LH) and follicle stimulating hormone (FSH), so AIs must be combined with a gonadotropin releasing hormone (GnRH) agonist to prevent the reflex LH and FSH increments. In advanced hormone-dependent breast cancer treatment, AIs have been shown to be superior to tamoxifen. Preliminary evidence also suggests superiority in the adjuvant, neoadjuvant settings and also for breast cancer prevention. AIs have been used in infertility and can increase ovulation rate. Reducing FSH dose, estrogen levels, improving response to FSH, implantation rates, and developing multiple follicles that can be used in in vitro maturation procedures are potential areas that AIs might be used in in assisted reproductive technologies (ART), besides simple ovulation induction. AIs are reported to be successful in treatment of endometriosis, an estrogen-dependent process. The use of AIs in gynecomastia, puberte precox, leiomyoma uteri, some estrogen-dependent cancers (ovarian), endometrial cancer and male infertility are reported; some of the results are promising but more clinical trials are needed. AIs are predicted to become the gold standard in the treatment of estrogen-dependent diseases in reproductive medicine in the near future.

Aromatase Inhibitors↗
PubMed2003

Growth hormone insufficiency and its impact on ovarian function.

Growth hormone (GH) and the insulin-like growth factor-I (IGF-I) play significant roles in pubertal development, menarche, the menstrual cycle, fertility, and reproduction. Growth hormone deficiency or insufficiency causes a delay in the onset of puberty and in its normal course unless treated with synthetic GH. It seems that GH affects the ovary during puberty both indirectly through the gonadotropins and IGF-I, and directly through its effect on steroidogenesis. The GH axis is activated by small increases in circulating estrogens, which initiate large increases in GH during puberty. The reproductive function of the female is also affected by GH. GH acts on the ovary affecting gametogenesis and steroidogenesis. GH receptor mRNA and protein have been found in ovarian cells, and this suggests that the direct action of GH provides an important modulatory effect on gonadotropin-dependent and -independent functions. It also affects the maturation of the follicle and gamete, and thereby plays a facilitatory role in fertility. The majority of women with GH-deficiency, but not all, require assisted reproductive technologies to induce ovulation. Many women with polycystic ovary syndrome (PCOS) have an impaired GH response to stimulation with Levo-Dopa and GH releasing hormone (GHRH). Hyperandrogenism in PCOS may contribute to the reduced GH secretion because testosterone directly stimulates somatostatin release. Reduction of the excessive androgens facilitates the dopaminergic control of GH. In conclusion, GH-insufficient states disrupt ovarian function, causing problems in sexual maturation, the menstrual cycle, and the reproductive ability of the female.

Adolescent↗