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PubMed2001

Reproductive compensation and human genetic disease.

The effects of reproductive compensation on the population genetics of sex-linked recessive lethal mutations are investigated. Simple equations are presented which describe these effects, and so complement existing population genetic theory. More importantly, this type of mutation is responsible for several severe human genetic diseases such as Duchenne muscular dystrophy. It is argued that the applications of three modern reproductive technologies--effective family planning, in utero diagnosis with termination, and embryo sexing--will lead to reproductive compensation. The adoption of any of these technologies may rapidly elevate the frequencies of those mutations which are lethal in childhood. This increase is large, in the order of 33% upwards, and occurs rapidly over two to five generations. It also depends on the source of mutations, the effect being larger if most mutations are paternal. In utero diagnosis and/or embryo sexing increase the frequency of the mutation, but simultaneously decrease disease incidence by preventing the birth of affected offspring. In contrast, effective family planning may rapidly increase both mutation frequency and disease incidence.

Family Planning Services↗
PubMed2006

Embryo production in dogs: from in vitro fertilization to cloning.

Increased availability of canine embryos would be desirable to develop research and to apply assisted reproductive technologies in the treatment of infertility and in the improvement of reproductive performances in valuable Canids, both domestic and non-domestic. Embryo production through in vitro fertilization and nuclear transfer has been technically achieved in the dog, and the transfer of cloned embryos has recently resulted in the birth of puppies. However, the efficiency of these technologies is still very limited. This is mainly because of the peculiar characteristics of the canine oocyte and the lack of its full acquisition of developmental competence in vitro. This paper discusses the latest results and aspects on which further research should be focused to provide advances in the field.

Animals↗
PubMed2006

Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro.

Oocyte in vitro maturation (IVM) is an important reproductive technology that generates mature oocytes that are capable of supporting preimplantation embryo development and full development to term. There is great clinical and commercial incentive to improve the efficiency of the technology, however, progress has been slow over the past decade. A critical challenge is to understand what constitutes oocyte developmental competence and the mechanisms governing it. We have taken the approach of studying in detail oocyte-somatic cell interactions; including, oocyte-cumulus cell (CC) gap-junctional communication, and bidirectional paracrine signalling between the two cell types. It is becoming clear that, compared to oocytes matured in vivo, IVM oocytes undergo maturation prematurely as they are still in the process of acquiring developmental competence in vivo, and the molecular cascade reinitiating meiosis differs entirely to that in vivo. Attempts to enhance oocyte developmental competence by attenuating the spontaneous meiotic resumption of oocytes in vitro have been met with mixed success. Kinase inhibitors that prevent maturation-promoting factor activity have, in general, been ineffectual on promoting oocyte developmental potential post-IVM. In contrast, agents that modulate oocyte cAMP during IVM show greater potential, possibly as these compounds extend oocyte-CC gap-junctional communication. An important concept that is now emerging is that the oocyte secretes potent growth factors that regulate fundamental aspects of CC function and thereby determine the distinctive phenotype of the cumulus-oocyte complex. The capacity of an oocyte to regulate its own microenvironment by oocyte-secreted factors (OSFs) may constitute an important component of oocyte developmental competence. In support of this notion, we have recently demonstrated that supplementing IVM media with exogenous OSFs improves oocyte developmental potential, as evidenced by enhanced pre- and post-implantation embryo development.

Animals↗
PubMed2003

HIV/AIDS in the shadows of reproductive health interventions.

In December 1999, the Tanzanian president declared HIV/AIDS a national disaster. By the time the National Policy on HIV/AIDS was released in 2001, an estimated 750,000 women of reproductive age were infected. Yet in spite of the impact of HIV on reproductive health, AIDS and reproductive health programmes are still thought of and implemented through separate channels, to the detriment of both. However, although AIDS remains in the shadows of reproductive health interventions, the lack of AIDS talk does not lessen the impact of the disease on people's lives. During the course of my participant observations in maternal and child health/family planning (MCH/FP) clinics collected during 25 months of fieldwork in 10 clinics in Morogoro, Ruvuma and Kilimanjaro Regions, I rarely heard about AIDS. This article attempts to analyse why. Historically competing bureaucracies in MCH/FP and gender and development are not easily unified with a vertical HIV/AIDS control programme under the umbrella of "reproductive health". HIV/AIDS cannot merely be inserted into existing family planning programmes, re-named "reproductive health" programmes. As the AIDS epidemic is transformed through new technologies, reproductive health policy and priorities will be called into question and force us to look at the state of the African health care system, networks of care-giving, and how individuals and communities fail when there is no socio-economic safety net.

Communicable Disease Control↗
PubMed2026

Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.

De novo mutations (DNMs) are an important source of congenital diseases. With delayed parenthood and assisted reproductive technology (ART) use increasing, it is essential to elucidate how these reproductive factors influence DNMs and whether resulting mutations influence offspring health. Here we performed whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families, identifying 390,924 de novo single-nucleotide variants (dnSNVs). Paternal and maternal aging exhibited distinct mutational patterns, with maternal DNM accumulation accelerating at advanced ages. Increased paternal dnSNVs partially accounted for the association between advanced parental age and shorter gestational duration. Moreover, ART showed age-independent, procedure-specific effects: intracytoplasmic sperm injection (ICSI) and ovarian stimulation were associated with increased paternal and maternal dnSNVs, respectively, and ICSI-associated paternal dnSNVs also partially accounted for the association between ICSI and shorter gestational duration. In vitro embryo manipulation was associated with increased early post-zygotic mosaic mutations, particularly C > A substitutions linked to delayed neurocognitive development at 1 year. Collectively, these findings advance understanding of the determinants and consequences of de novo mutagenesis.

Journal Article↗
PubMed1997

Genetics of reproduction and its evolutionary significance.

PROBLEM: To provide an evolutionary perspective on reproductive problems. METHOD OF STUDY: A broad range of evolutionary and reproductive data in the literature were analyzed. RESULTS: Evolutionary considerations provide some insight into two aspects of human reproduction. First, the inefficiency of the reproductive process (20-35% of fertilized ova yield successful pregnancies) may reflect the stress placed on the reproductive process by the relatively short evolutionary time between the hunter--gatherer and settled agricultural patterns of human life. Second, the immaturity of the immune response of the human newborn is most likely a consequence of its delivery while still in the embryonic/fetal stage of development. Delivery at this time is necessitated by the rapid development of the human brain in utero. CONCLUSIONS: The attempts to develop reproductive technologies should take into account the fundamental limits on the human reproductive process. A variety of in utero preventive and therapeutic techniques should be developed to provide the newborn with enhanced resistance to infectious diseases or to correct congenital defects. All new procedures should be thoroughly investigated and proved before being put into clinical practice.

Animals↗
PubMed1995

Assisted conception techniques. On what basis do health technologies become routinely available when they have been assessed as effective?

The possibility of restoring fertility among some infertile couples through assisted reproductive technology has led to questions about the terms under which such treatments should be made available. Although there is now evidence on their effectiveness, there is considerable variation in the availability of these treatments under the U.K. National Health Service.

Diffusion of Innovation↗
PubMed1996

Electroejaculation and assisted reproductive techniques for anejaculatory infertility.

OBJECTIVE: To report our experience with electroejaculation combined with intrauterine inseminations (IUI) and other assisted reproductive technologies. METHODS: Anejaculatory men desirous of fertility were evaluated in our Assisted Reproductive Program. Between March 1991 and December 1994, 26 men (age 24-48) underwent a total of 84 electroejaculations. Causes of anejaculation included spinal cord injury (n = 23) and retroperitoneal lymph node dissection (n = 3). Female partners were super-ovulated to improve the pregnancy rate. The success in sperm retrieval and pregnancy rates were determined, and the quality of electroejaculates was evaluated. RESULTS: Seventy-seven of 84 (92%) electroejaculations were successful, defined by retrieval of more than 10 x 10(6) total and more than 10(6) motile spermatozoa. Mean sperm count was 65 million/mL (range 0-569), but mean motility was only 16% (range 0-66). Mean normal morphology was 27% (range 0-71). Ten couples attempted conception. Fifty cycles of IUIs were performed, resulting in four normal term infants and one spontaneous abortion (pregnancy rate 10% per IUI). One patient failed to conceive with eight cycles of IUIs but became pregnant with in vitro fertilization-embryo transfer with micromanipulation using electroejaculates; she delivered a set of healthy twins. Two couples elected donor sperm insemination after failing to conceive by IUI with electroejaculates; both became pregnant. CONCLUSION: Electroejaculation offers an encouraging pregnancy opportunity for anejaculatory men who otherwise are considered infertile. Marked asthenospermia is observed in electroejaculates, the etiology of which remains obscure. Further studies to elucidate the cause may improve pregnancy rates.

Adult↗
PubMed1997

Assisted reproduction and reproductive rights: the case of in vitro fertilization.

In vitro fertilization (IVF) and other assisted reproduction technologies (ARTs) have become widely accepted as therapy for a wide array of fertility problems and accompanied by the rapid expansion of clinics that provide full range of ARTs. Although these technologies undoubtedly offer benefits for some individuals, they raise important questions over reproductive rights to safe and effective treatment as well as access. This article analyzes current data concerning the safety, effectiveness, and cost of IVF. It concludes that IVF and related techniques have been transformed too rapidly and easily from experimental to therapy status, despite evidence that suggests considerable caution is warranted. Unfortunately, the widespread diffusion of IVF has preceded rather than followed firm evidence of its value in extending the reproductive rights of women and couples. Resources might better be directed toward prevention of fertility problems and discovering the causes of infertility.

Cost-Benefit Analysis↗
PubMed1997

Genetic factors in reproduction and their evolutionary significance.

PROBLEM: The reproductive process is a major driving force in human evolution. An evolutionary perspective was brought to bear on some aspects of reproduction and its aberrations, and, conversely, some of the insights of modern reproductive genetics were used to investigate problems in evolution. METHOD: The data used were obtained from the literature in evolution, anthropology, archeology, linguistics, and genetics. RESULTS: The evolutionary line leading to modern humans diverged from that leading to the chimpanzees approximately 5-7 million years ago (Mya). Archaic Homo sapiens emerged ca. 0.3 Mya, and modern Homo sapiens and the development of language ca. 0.1 Mya; thus, modern humans occupy approximately 2% of the evolutionary history of the hominid line. During all of this time, the ancestors of modern humans were migratory hunter-gatherers. It was only during the Neolithic transition ca. 0.01 Mya (approximately 0.2% of hominid evolutionary history) that agriculture was developed, and with it a settled lifestyle that allowed a more stable existence and the development of a different reproductive pattern. Various estimates indicate that the human population increased from 0.05 million at the time of the emergence of modern Homo sapiens to 6,000 million at the present time (120,000-fold increase). CONCLUSIONS: These evolutionary considerations were used to explore three areas: (1) the extinction of the Neanderthals, who coexisted for ca. 65,000 years with modern humans; (2) the relatively low and stable rate of human conceptions (20-35% of ova fertilized naturally or fertilized in vitro); and (3) the long postnatal period required for the full maturation of the immune response. From these considerations, a broad view of the human reproductive process was obtained that may provide some insight into the rationale for the development of effective reproductive technologies.

Animals↗
PubMed2005

Embryo technologies and animal health - consequences for the animal following ovum pick-up, in vitro embryo production and somatic cell nuclear transfer.

Mammalian reproductive technologies that aim either to complement or to transcend conventional livestock breeding options have contributed to some of the most remarkable achievements in the field of reproductive biology in recent decades. In so doing they have extended our horizons in two distinct dimensions, the first concerning what it is technically possible to achieve and the second relating to the time-frame within which an individual's life-long developmental capability is initially established and ultimately realized or undermined. Our impressions of the benefits and values, or otherwise, of technologies such as in vitro embryo production and nuclear transfer are rightly influenced by the extent to which they impinge on the health of animals either subjected to or derived from them. Here, we consider some of the health implications of oocyte/embryo-centric technologies applied to farm livestock.

Animal Welfare↗
PubMed2003

Chaotic mosaicism in human preimplantation embryos is correlated with a low mitochondrial membrane potential.

OBJECTIVE: To determine the relationship between the intrinsic mitochondrial deltapsi of human embryos and the embryo karyotype. DESIGN: Analysis of mitochondrial deltapsi of living embryos followed by chromosomal enumeration with fluorescence in situ hybridization. A tertiary center for assisted reproduction technology. PATIENT(S): Fifty-two patients attending the fertility center for assisted reproduction. INTERVENTION(S): Donated embryos were loaded with a mitochondrial deltapsi-sensitive fluorescence dye. MAIN OUTCOME MEASURE(S): Mitochondrial deltapsi was measured by confocal microscopy. Subsequently, embryos were fixed and fluorescence in situ hybridization analysis was used to denote embryo karyotype. MAIN OUTCOME MEASURE(S): Mitochondrial deltapsi and embryo karyotype. RESULT(S): An association was observed between low mitochondrial deltapsi and the detection of chaotic mosaicism. Analysis of oocytes suggested that this was due to the effect of low mitochondrial deltapsi on the morphology of the meiotic apparatus. CONCLUSION(S): The data suggest that the intrinsic mitochondrial deltapsi of human oocytes programs the developmental fate of embryos through an effect on the ability of oocytes to form a normal meiotic apparatus and not through nondisjunction.

Blastocyst↗
PubMed1997

Ethical issues relating to reproduction control and women's health.

There are many ethical aspects which derive from the application of reproduction control in women's health. Women's health can be enhanced if women are given the opportunity to make their own reproduction choices about sex, contraception, abortion and application of reproductive technologies. The main issues that raise ethical dilemmas following the development of assisted reproduction techniques are: the right to procreate or reproduce; the process of in vitro fertilization itself-is it morally acceptable to interfere in the reproduction process?; the moral status of the embryo; the involvement of a third party in the reproductive process by genetic material donation; the practice of surrogacy, cryopreservation of pre-embryos; genetic manipulation; experiments on pre-embryos, etc. Induced abortion raises ethical issues related to the rights of the woman versus the rights of the fetus. For those who consider life to begin at conception abortion always equals murder and is therefore forbidden. Those who believe in the absolute autonomy of the woman over her body take the other extreme approach. The discussion surrounding abortion usually centers on whether it should be legal or illegal. Access to safe abortion is critical to the health of women and to their autonomy. The development of new effective contraceptive methods has a profound impact on women's lives. By the use of contraception it is possible to lessen maternal, infant and child mortality and to reduce the prevalence of sexually transmitted diseases. Research and development of new effective reversible contraceptives for women and men is needed. Dissemination of information about the safety and effectiveness of contraceptive methods is of great importance. Female genital mutilation is still practiced worldwide due to customs and tradition among various ethnic groups. The procedure is considered to be medically detrimental to the physical and mental health of women and girls, and is considered by many as oppression of women. The practice has to be stopped. Recognition of the fetus as a 'patient' has a potential effect on women's right for autonomy; they have no legal obligation to undergo invasive procedures and to risk their health for the sake of their fetuses. The woman carries ethical obligations toward her fetus. This obligation should not be enforced by the law. At present women bear most of the burden of reproductive health. All of them have a right of access to fertility regulation. Governments and society must ensure the women's equal rights to health care just as men have in the regulation of their fertility.

Abortion, Induced↗
PubMed2001

Molecular cloning of three nonhuman primate follicle stimulating hormone beta-subunit cDNAs.

The follicle stimulating hormone (FSH) beta-subunit cDNAs were cloned and sequenced for an old world primate, the rhesus monkey (Macaca mulatta), and two New World primates, the common marmoset (Callithrix jacchus) and pygmy marmoset (Cebuella pygmaea). The cDNA and predicted amino acid sequences of the rhesus monkey FSH beta-subunit were related most closely to the human FSH beta-subunit (> 96% identity). The common and pygmy marmosets have identical FSH beta-subunit cDNAs, whereas the marmoset FSH beta-subunit diverges from the rhesus and human molecules with less than 93% identity. These results have significance for the implementation of assisted reproductive technologies in the nonhuman primate as well as the evolution of genes encoding reproductive hormones.

Amino Acid Sequence↗
PubMed2003

Human assisted procreation and human rights--the Greek response to the felt necessities of the time.

The new reproductive technologies enable otherwise infertile couples to reproduce noncoitally. Problems arising from the new reproductive techniques refer to the persons entitled to have access thereto, to the methods accepted (such as procreation by means of a surrogate mother), to the storage and donation of gametes and embryos, to donor anonymity etc. Although homologous and heterologous insemination and in vitro fertilisation have been performed in Greece for a long time, legal provisions thereon have been established only recently: Law 3089/2002 on assisted procreation builds the respective legal frame, regulating main aspects in this crucial field of interwoven human rights and social duties.

Female↗
PubMed1991

Reproductive transplantations: the present and future.

Transplantation of reproductive organs have been unsuccessful to date because transplantation models utilised have never taken into consideration the vascular models of the reproductive system especially that of the female. This article examines the future of large organ transplantation in reproductive system and also the transplantation of cellular and tissue components as in embryo transfers. It also examines the future of such research procedures as embryo splicing, nuclear gene injections and transplantation in reproductive technologies.

Female↗
PubMed2006

Cancer genetic testing and assisted reproduction.

PURPOSE: Because of increasing uptake of cancer genetic testing and the improving survival of young patients with cancer, health care practitioners including oncologists will increasingly be asked about options for assisted reproduction by members of families affected by hereditary cancer syndromes. Among these reproductive options, preimplantation genetic diagnosis (PGD) offers the opportunity to select embryos without familial cancer-predisposing mutations. METHODS: A review of the published literature supplemented by a survey of PGD centers in the United States. RESULTS: Prenatal diagnosis and/or embryo selection after genetic testing has already been performed in the context of more than a dozen familial cancer syndromes, including the common syndromes of genetic predisposition to colon and breast cancer. CONCLUSION: While constituting new reproductive options for families affected by cancer, the medical indications and ethical acceptance of assisted reproductive technologies for adult-onset cancer predisposition syndromes remain to be defined. Continued discussion of the role of PGD in the reproductive setting is needed to inform the responsible use of these technologies to decrease the burden of heritable cancers.

Breast Neoplasms↗