Research Article
Preimplantation genetic diagnosis
- Yury Verlinsky, Anver Kuliev
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- Published online by Cambridge University Press:
- 01 March 1999, pp. 1-10
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Preimplantation diagnosis of inherited and chromosomal diseases allows couples at risk of conceiving a genetically abnormal fetus to avoid the birth of an affected child without the need for a prenatal diagnosis and selective abortion of an affected fetus. For some couples this may be the only option, because they cannot accept termination of pregnancy as a measure of avoiding the birth of an affected child. Even for those who accept prenatal diagnosis, repeated termination of pregnancy forces them to look for other options to control the outcome of their pregnancies from the very outset. This may be achieved by genetic analysis of oocytes or cleaving embryos, which opens a new prospect for ‘prepregnancy’ genetic diagnosis. As will be shown, such an approach will also be a useful addition to assisted reproduction technologies, at least for in vitro fertilization (IVF) patients of advanced maternal age.
The physiology of ovarian oxytocin
- Richard Ivell
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- Published online by Cambridge University Press:
- 01 March 1999, pp. 11-25
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The notion of an oxytocic principle residing within the ovary is not new. In as early as 1910, Ott and Scott showed that an extract of bovine corpus luteum could induce milk letdown and uterine contraction. However, it took a further 70 years before the identification of this principle with the nonapeptide hormone oxytocin (OT) was made at the peptide and mRNA levels. This was followed by the identification of the peptide in ovarian tissues and ovarian venous blood from a wide variety of species, including humans, monkeys, pigs and ruminants (reviewed in 7, 8). For the majority of non-ruminant species the levels of expression of the peptide and its specific mRNA are relatively low, implying that whatever function the ovarian hormone has in these species, it is most likely to be at the local, paracrine level. Ruminants are an exception. Cows and sheep both produce very high levels of OT and OT-mRNA – the latter attaining concentrations of approximately 1% of all transcripts – within the corpus luteum of the early oestrous cycle. In ruminants, evolution has culminated in a systemic link between ovarian OT production and OT receptors in the endometrium of the uterus, inducing there the production of prostaglandin-F2∞ (PGF2∞) which completes a positive feedback loop to the ovary by stimulating further OT release (reviewed in 10). It is important to note, however, that natural selection can only act on a preexisting system. In this case, it has developed a systemic endocrine pathway in ruminants from a local ovarian OT system present probably in all mammals. There is even evidence for OT-related peptides, such as mesotocin and vasotocin, within the ovaries of marsupials and chicken, though their function is not known.
Adjunctive medical treatments in follicular stimulation
- Bryan D Cowan
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- 01 March 1999, pp. 27-39
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Approximately 25% to 35% of couples that seek infertility services suffer from defects in ovulation.This diagnosis represents the single leading cause of infertility disorders, and makes medical ovulation induction the most common intervention for the treatment of infertility. There are two classes of correctable ovulation defects, and correct classification is correlated with treatment and prognosis. World Health Organization (WHO) I patients have ovulation defects associated with low estrogen and low gonadotropin levels and fail to exhibit withdrawal bleeding after progestin challenge. WHO II ovulation disorders occur in estrogenized/androgenized women who, in general, menstruate. Other names for these conditions include hypogonadotropic hypogonadism (WHO I) and polycystic ovarian disease (WHO II).
The role of maternal age in the assisted reproductive technologies
- Mark A Damario, Owen K Davis, Zev Rosenwaks
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- Published online by Cambridge University Press:
- 01 March 1999, pp. 41-60
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Age is perhaps the most important single variable influencing outcome in the assisted reproductive technologies (ART). The effect of advancing age on clinical ART outcome is manifested not only in the pattern of ovarian response to stimulation regimens, but also in reduced implantation efficiency and an increased spontaneous abortion rate. The clinical importance of these factors is compounded by the fact that increasing numbers of older women are presenting for ART treatment. Delayed childbearing is becoming increasingly common in the western world. The availability of methods of birth control, educational and career priorities for women, and the increased rates of divorce and remarriage are some of the factors contributing to this phenomenon.
Age and reproduction
- José R Cruz, Paul R Gindoff
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- 01 March 1999, pp. 61-69
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Advanced female reproductive age is an important factor when evaluating couples for infertility. Infertility is defined as a lack of pregnancy after 12 months of unprotected intercourse, a condition present in about 15% of couples of reproductive age. The proportion of couples considered infertile has not changed recently in spite of an increase in the number of couples seeking infertility evaluation and treatment. Reasons for this phenomenon include the aging of the baby-boom generation, deferment of childbearing to later years of reproductive life (because of changes in lifestyles), and increased exposure of patients to infertility services. More women are delaying childbearing until their late 30's and into their 40's for various reasons, one of them being to develop their professional careers. This voluntary delay in childbearing not only poses a problem in terms of the 30–50% reduced pregnancy potential of older women, but other risks also have to be taken into account: the effect of pregnancy on other maternal illnesses, an increased risk of pre-eclampsia, hypertension and diabetes, and an increased risk of chromosomal abnormalities, abortions, and stillbirth. The decrease of female fecundity beginning in the 30's, becoming more pronounced after 40, is well documented. There is an approximately 50% decrease in the fertility rate of women attempting pregnancy at the age of 40 or older compared with younger women, and a twofold to threefold increase in the rate of spontaneous abortions. Reports of artificial insemination and chromosomal analysis of unfertilized human oocytes and spare embryos in in vitro fertilization (IVF) suggest that the quality of the oocyte and the resulting embryo are affected seriously by age; again, an age of 40 years being the critical cutoff point. On the other hand, age (up to 64 years) does not seem to affect sperm characteristics or its ability to fertilize human eggs, and the resulting embryo development in vitro as well as implantation in recipient uteri are not affected by the age of the male providing the semen sample.