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PubMed2006

The role of free radicals and antioxidants in reproduction.

PURPOSE OF REVIEW: This review summarizes the role of free radicals and oxidative stress in the pathophysiology of human reproduction. RECENT FINDINGS: An extensive review of the literature on the role of oxidative stress in influencing assisted reproduction and its outcome is described in this article. Free radicals or reactive oxygen species mediate their action through many of the proinflammatory cytokines and this mechanism has been proposed as a common underlying factor for endometriosis, ovarian cancer, polycystic ovary disease, and various other pathologies affecting the female reproductive process, as highlighted in this review. Oxidative stress, sperm DNA damage, and apoptosis have been implicated in male infertility. Elevated reactive oxygen species levels correlate with the poor fertility outcomes seen in the assisted reproductive technology setting. SUMMARY: Oxidative stress has been implicated in male and female infertility, including fetal dysmorphogenesis, abortions, and intrauterine growth restriction. Accurate evaluation of seminal oxidative stress by standardized assays may help in the diagnosis and management of male infertility. There is evidence in the literature on the beneficial effects of oral antioxidant supplementation in male infertility. Current ongoing trials will provide answers on the safety and effectiveness of antioxidants in improving maternal and fetal outcomes. Further studies need to be conducted to determine if antioxidant supplementation will prevent fetal developmental defects in high-risk pregnancy with diabetes.

Antioxidants↗
PubMed1991

The Davis dilemma: how to prevent battles over frozen preembryos.

Cryopreservation of preembryos, or the freezing of fertilized human eggs, is a procedure increasingly used by infertile couples to improve the odds of success of advanced reproductive technologies. As a consequence, divorcing couples are finding themselves in dispute over the disposition of frozen preembryos that have not been implanted. Courts have been called on to decide to whom the frozen preembryos should be awarded, but the law is unclear whether frozen preembryos should be treated as marital property, as children, or as something else. The author analyzes various arguments concerning the appropriate legal status of frozen preembryos, and suggests a new rule to settle such disputes.

Beginning of Human Life↗
PubMed2004

Bilateral ovarian pregnancy after in vitro fertilization and embryo transfer in a patient with tubal factor infertility.

Primary ovarian pregnancy is very rare event after natural pregnancy or assisted reproductive technology (ART) procedures. Although there are a few reports about unilateral ovarian pregnancy after in vitro fertilization and embryo transfer (IVF-ET), there has been no report about bilateral ovarian pregnancy. Moreover, it is difficult to diagnose an ovarian pregnancy following in vitro fertilization and embryo transfer because of enlarged ovary, fluid collection in pelvic cavity, and its low incidence. We present a case of a patient who underwent IVF-ET due to tubal factor infertility, but the patient developed bilateral ovarian pregnancy and was performed both ovarian wedge resection through laparotomy.

Adult↗
PubMedDate not supplied

Care for the beginning of life. The revised Ethical and Religious Directives discuss abortion, contraception, and assisted reproduction.

Part 4 of the Ethical and Religious Directives for Catholic Health Care Services--which discusses such controversial issues as abortion, contraception, and assisted reproduction--is informed by a profound respect for human life and the institution of marriage. The controversies are familiar. But many in Catholic healthcare may be less familiar with the principles underlying Church teaching on these issues. Appropriate interpretation and application of these directives require that all concerned be educated in both the theological-ethical and the clinical dimensions of care giving. Directives 38 through 43 deal with reproductive technologies such as in vitro fertilization and surrogacy. Directives 52 and 53 express the Church's consistent teaching on contraceptive interventions. Directives 45 to 48, 50 to 51, and 54 reiterate the Church's firm stance on the inviolability of human life, including nascent human life. However, the directives also say that not all medical interventions resulting in fetal death are prohibited abortions. However, appropriate regard for human life, marriage, and the family require more than mere adherence to the directives' prescriptions and proscriptions. Ethics committees in Catholic healthcare should study clinical data as well as theological materials.

Abortion, Induced↗
PubMedDate not supplied

Preservation of fertility and ovarian function and minimizing chemotherapy-induced gonadotoxicity in young women.

BACKGROUND: After the improved long-term survival in young women with lymphoma and leukemia undergoing chemotherapy, the preservation of future fertility has been the focus of recent interest. AREAS OF REVIEW: Three major topics are reviewed. They include the following: (1) the role of chemotherapy in the treatment of malignant and nonmalignant disease in young women, the types of chemotherapy and their gonadal effects (differing between ovaries and testes) in both human and other species, and the reasons for differences in the outcomes of various studies; (2) the human experience with GnRH-agonist therapy for minimizing chemotherapy-associated gonadotoxicity; and (3) inhibin measurements in young women treated by chemotherapy and in perimenopausal patients and those with impending premature ovarian failure (POF). Whereas egg retrieval for in vitro fertilization (IVF) and embryo cryopreservation is a valid assisted reproductive technology (ART) for married couples, it may be unacceptable for the young single woman. The investigational endeavors of ovarian cryopreservation awaits the clinical experience of in vitro maturation of thawed primordial follicles, their IVF, and embryo transfer. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cryopreserved ovary has been raised after animal observations. Therefore, until these innovative endeavors prove successful, and in parallel with them, an attempt was made to minimize the gonadotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic analogue (GnRH-a) to induce a temporary prepubertal milieu, because prepubertal ovaries were found more resistant to alkylating agents' effect than the ovaries of older women. To characterize the correlation with ovarian function after gonadotoxic chemotherapy for Hodgkin or non-Hodgkin lymphoma in young women, the immunoreactive inhibin-A concentrations in the sera of these patients were measured before, during, and after the gonadotoxic chemotherapy. CONCLUSIONS: The GnRH-a cotreatment should be considered in every woman in the reproductive age receiving chemotherapy, in addition to ART and the investigational attempts of ovarian cryopreservation for future in vitro maturation or reimplantation. If these preliminary data are confirmed in a larger group of patients, inhibin-A concentrations may serve as a prognostic factor for predicting the resumption of ovarian function in addition to the levels of FSH, LH, and estradiol.

Antineoplastic Agents↗
PubMed2006

Obstetric complications and perinatal outcome in triplet pregnancies.

The incidence of multiple pregnancies with more than two fetuses has significantly increased since the introduction of ovulation agents and assisted reproductive technologies. Over a 15-year period there were 35 triplet pregnancies beyond 24 weeks that delivered at the King Fahad Hospital, an incidence of 1 in 1,099 deliveries. Early diagnosis is important for improving the rate of fetal salvage in triplet pregnancy. These pregnancies were managed on an outpatient basis. Prophylactic interventions were not utilised. A total of 91% of the pregnancies had at least one antenatal complication, pre-term labour being the most common (80%) followed by anaemia (43%). The average gestational age at delivery was 31.7 weeks (SD 4.2 weeks). A total of 94.3% of the patients were delivered by lower segment caesarean section. The mean birth weight of the neonates was 1,552 g (SD 510 g) and mean 5-min Apgar score was 7.6 (SD 0.8). The corrected perinatal mortality rate in the study was 152/1,000. Pregnancy outcome did not vary with birth order or mode of conception. Higher rate of pre-term births among triplet pregnancies make considerable demands on the neonatal intensive care unit. All methods of assisted reproduction should aim at prevention of multifetal pregnancies.

Adult↗
PubMed1999

Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome.

To test the hypothesis that dimeric inhibin A and/or inhibin B concentrations represent improved markers of in-vitro fertilization (IVF) outcome over follicle stimulating hormone (FSH), 78 women who achieved pregnancy within three assisted reproduction treatment cycles were matched to 78 women who underwent at least three assisted reproductive treatment cycles and failed to achieve pregnancy. Baseline serum inhibin B and FSH were obtained between days 1 and 4 in a cycle prior to ovarian stimulation, and inhibin A and B were measured immediately before the ovulatory stimulus and in follicular fluid from the lead follicle. Comparing pregnant and non-pregnant subjects at baseline, younger age (34.0 +/- 0.5 versus 36.0 +/- 0.5 years; P < 0.003) and a combination of FSH lower than the median value (11.2 IU/l) and inhibin B higher than the median value (76.5 pg/ml) were associated with pregnancy (P < 0.03), but FSH (11.7 +/- 0.5 versus 12.9 +/- 0.9 IU/ml) and inhibin B (89.0 +/- 10.2 versus 79.7 +/- 7.7 pg/ml) were not independently associated. At the time of the ovulatory stimulus, serum inhibin A (52.8 +/- 3.8 versus 40.0 +/- 2.7 IU/ml; P < 0.004), inhibin B (1623.8 +/- 165.1 versus 859.2 +/- 94.8 pg/ml; P < 0.0009) and the number of oocytes retrieved (14.6 +/- 0.8 versus 10.1 +/- 0.6; P < 0.0001) were predictive of pregnancy when controlled for age. Inhibin A was correlated with the number of embryos (r = 0.4; P < 0.0001). However, neither inhibin A nor inhibin B provided additional information in predicting successful outcome over age and number of oocytes. We conclude that: (i) in patients undergoing assisted reproductive technology, age and number of oocytes retrieved are the strongest predictors of success; (ii) of the parameters available prior to cycle initiation, a combination of lower FSH and higher inhibin B was associated with a greater chance for a successful outcome but an absolute cut-off could not be defined; and (iii) during ovarian stimulation, higher concentrations of inhibin A and inhibin B in serum are associated with successful IVF and mark ovarian reserve as a measure of oocyte number and quality.

Adult↗
PubMed2006

What can the clinician do to improve implantation?

Implantation is a complicated process that requires the orchestration of a series of events involving both the embryo and the endometrium. Even with the transfer of high quality embryos, implantation rates remain relatively low. The growing tendency towards transferring fewer embryos provides further incentives to improve implantation rates. In this article, the various clinical strategies employed to increase the chance of implantation are reviewed. Embryo transfer technique is a critical step in assisted reproductive technology cycles. Recent studies have shown significant improvements in clinical pregnancy rates resulting from careful embryo transfer technique, appropriate catheter type and placing for embryo transfer. Increasingly, adjuvant pharmaceutical therapies are also being applied with the aim of improving embryo implantation. However, the evidence for their efficacy and safety is limited. Recent evidence suggests that adoption of milder ovarian stimulation regimens may provide a more effective clinical approach to improving implantation, since beneficial effects have been shown for both endometrial receptivity and embryo quality.

Aromatase Inhibitors↗
PubMed2006

Application of laser-assisted zona drilling to in vitro fertilization of cryopreserved mouse oocytes with spermatozoa from a subfertile transgenic mouse.

Development of assisted reproductive technologies is necessary to obtain fertilized oocytes in a subfertile transgenic mouse strain. Here, we showed the application of laser-assisted drilling of the zona pellucida to in vitro fertilization of cryopreserved mouse oocytes with sperm from subfertile transgenic mice (C57BL/6N-Tg(UCP/FAD2)U8 strain). After cryopreservation by vitrification, the recovery and survival rates of the zona-drilled mouse oocytes were 97% (97/100) and 94% (91/97), respectively. In vitro fertilization of the cryopreserved zona-drilled mouse oocytes with sperm from the subfertile transgenic mice was greatly facilitated (60%, 55/91) compared to that of the cryopreserved zona-intact mouse oocytes (11%, 81/768). In vitro fertilized embryos that developed to the 2-cell stage were again cryopreserved by vitrification, and after warming they were transferred into recipient females. Subsequently, six viable offspring were delivered, and all were confirmed to be transgenic mice. These results indicate that laser-assisted zona drilling of oocytes combined with cryopreservation by vitrification may be a useful approach for large-scale production of in vitro fertilized embryos for managing transgenic mouse strains with reproductive disabilities such as subfertile sperm.

Animals↗
PubMed2004

Yq microdeletions--azoospermia factor candidate genes and spermatogenic arrest.

In the last few years considerable progress has been made in the study of sperm physiology and the biology of gamete interaction, furthering our understanding of the pathophysiology of male infertility. With the advent of assisted reproductive technology and intracytoplasmic sperm injection, study of the various factors leading to spermatogenic impairment has become a major focus of scientific research. Understanding the genetic factors that lead to infertility has taken on a certain urgency, as we have learned not only of the transmission to male offspring of spermatogenic impairment, but that these offspring may also be born with a secondary, larger deletion with worsening of phenotype and genital ambiguity. Ten to twenty-five percent of couples encounter difficulty procreating. Microdeletions of the long arm of the Y chromosome are associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb, and AZFc) that are critical for spermatogenesis. This study was conceived in order to identify the frequency of submicroscopic interstitial deletions in azoospermia factor loci in infertile Indian males. One hundred and seventy five males with nonobstructive oligozoospermia and azoospermia were included in this study. Semen analysis was done in each case to determine the spermatogenic status-normospermic, oligozoospermic (< 20 million sperm/mL), or azoospermic (no sperm in the semen). Detailed medical, clinical, reproductive, and family histories were taken of each patient. Thirty G-banded metaphases were analyzed in each case and polymerase chain reaction microdeletion analysis was done in 133 cytogenetically normal cases. For this genomic, DNA was extracted using peripheral blood. The sequence tagged site primers tested in each case were sY84, sY86 (AZFa); sY113, sY116, sY127, sY134 (AZFb); sY254, sY255 (AZFc). Polymerase chain reaction amplifications found to be negative were repeated at least three times to confirm the deletion of a given marker. The polymerase chain reaction products were analyzed on a 1.8% agarose gel. Eight of the 133 cases showed deletion of at least one of the sequence tagged site markers. Review of the literature has shown that the overall frequency of microdeletions varies from 1% to 55%. In the present study the frequency of microdeletion was 6.01%. Deletions were detected in cases with known and unknown etiology with bilateral severe testiculopathy.

Chromosome Aberrations↗
PubMed2006

Metabolic effects of obesity on reproduction.

Obese women are characterized by similar comorbidities to men, particularly type 2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some specific problems, including fertility-related disorders and some hormone-dependent forms of cancer. The relationship between excess body fat and reproductive disturbances appears to be stronger for early-onset obesity. Early onset of obesity, particularly during adolescence, favours the development of menses irregularities, chronic oligo-anovulation and infertility in adulthood. Moreover, obesity in women can increase the risk of miscarriage and impair the outcome of assisted reproductive technologies. The main factor implicated in the association between obesity and fertility-related disorders is insulin excess, which accompanies insulin resistance. Hyperinsulinaemia may be directly responsible for the development of androgen excess, through its effects in reducing sex hormone-binding globulin synthesis and circulating concentrations, and in stimulating ovarian androgen production rates. Androgen excess, in turn, represents one of the major factors leading to altered ovarian physiology and associated ovulatory disturbances. Obesity-associated hyperleptinaemia may represent an additional factor involved in anovulation, not only through the induction of insulin resistance, but also through a direct impairment of ovarian function.

Androgens↗
PubMed2001

Cryopreservation of human sperm.

Freezing of human sperm is considered a routine procedure in assisted reproductive technology (ART) laboratories. This article considers various aspects of cryopreservation of human sperm. Human sperm show a specific cryophysical behaviour and different sperm freezing protocols have been developed to avoid damage to the sperm cells. The damage can range from impaired motility and reduced viability to damage to the cellular organelles and effects at the molecular level, resulting in an impaired fertilizing potential. As testicular sperm are immature and only a small number can be retrieved, special techniques are required for successful freezing and thawing of these samples. Banking of human sperm has to be performed in a safe and controlled way and different guidelines are necessary to ensure that this is achieved.

Cell Survival↗
PubMed1993

Prenatal genetic testing and geneticization: mother matters for all.

Prenatal genetic testing represents the most widespread human application of reproductive technology, and its use is necessarily gendered. Moreover, its application both reflects and generates the process of 'geneticization' that increasingly orients contemporary western-world stories of health and disease. Taking a woman-centered approach, this paper examines some of the stories being told about testing; questions their themes of 'reassurance' and 'choice', their construction of 'risk', and their assumptions about disability; and explores the 'life-style' testing creates for (pregnant) women. Testing itself, and its power to control how we live and the children we bear, raises complex and troubling matters that require continued and fresh examination.

Abortion, Induced↗
PubMed1994

Ultrasonographic predictors of implantation after assisted reproduction.

OBJECTIVE: To assess the utility of endometrial thickness, echogenic endometrial pattern, and uterine artery impedance measured as pulsativity index in predicting implantation. DESIGN: Prospective case-controlled study of infertile patients undergoing assisted reproductive technologies (ARTs). PATIENTS: Four hundred five women undergoing ARTs were studied: 100 women after ET of thawed embryos in natural cycles (frozen ET), 107 women after standardized IVF-ET, 99 women receiving donor oocytes after controlled endometrial development with estrogen and P, and 99 women undergoing IUI with various ovarian stimulation regimens (none, 16; GnRH, 7; clomiphene citrate [CC], 29; hMG, 47). INTERVENTIONS: Transvaginal ultrasonographic examination performed on the day of hCG administration during stimulated cycles; on E2 day 15 during controlled endometrial cycles; and on the day of ovulation during natural, CC, and GnRH pump cycles. MAIN OUTCOME MEASURE: The endometrial thickness, echogenic pattern, and pulsativity index results in 170 conception cycles were compared with 235 nonconception cycles. RESULTS: When conception and nonconception cycles were compared, no difference in mean endometrial thickness and significant differences in the frequency of nonmultilayered pattern and pulsativity index > 3.3 were observed. Forty-seven percent of nonconception and 9% of conception cycles were associated with at least one of these factors. CONCLUSION: Ultrasonic measurements of pulsativity index, resistance index, and echogenic pattern are useful in predicting implantation after assisted reproduction.

Case-Control Studies↗
PubMed2003

Fetal development after assisted reproduction--a review.

Despite the success of assisted reproduction technologies (ART) in allowing conception in couples with infertility problems, a growing body of evidence points to implication of ART on fetal birth weight alterations, fetal malformations, chromosomal aneuploidies and syndromes related to genomic imprinting modifications. Different causes can be accounted for to explain the increased risk of fetal defects. Pregnancies generated by ART differ from spontaneously achieved pregnancies in that gametes and embryos are cultured in vitro, more than one conceptus is transferred into the uterine cavity, and the time of transfer is different to what occurs in normal conditions. Epigenetic reprogramming of gene expression has been advocated in relation to the gamete and embryo manipulation, with a significant role of genomic imprinting in determining changes in fetal growth. Moreover, the maternal environment, with the ovarian hyperstimulation of the beginning of pregnancy, could alter the maternal response to the early phases of trophoblast invasion. There are suggestions that placental weights and placental/fetal weight ratios are increased in these pregnancies resembling the model of maternal undernutrition in the early phases of pregnancy. Therefore concern has also arisen around the possible long term and transgenerational effects of assisted reproduction procedures and studies should be carried out to evaluate these possibilities.

Adult↗
PubMed2001

Nuchal translucency measurement and pregnancy outcome after assisted conception versus spontaneously conceived twins.

BACKGROUND: Nuchal translucency (NT) measurement for Down's syndrome screening or detecting various fetal anomalies is a reliable sonographic marker. This study evaluates the contribution of NT screening in spontaneously conceived and assisted conception twin pregnancies. METHODS AND RESULTS: Maternal age at measurement, chorionicity, ultrasound features, karyotype results and pregnancy outcome were recorded prospectively and compared in 83 assisted reproduction treatment and 91 spontaneously conceived twins. Pregnancy outcome was evaluated according to maternal age, method of conception, NT data and chorionicity. NT measurements (> or =95 centiles of the normal range) were considered screen-positive and mid-pregnancy fetal karyotyping was advised. Complicated pregnancy outcome, which could be signalled by increased NT, was defined as either chromosomal abnormalities, severe structural defects or fetal demise. Based on NT measurements, 16 fetuses (4.6%) were found to be screen-positive. Five of them had chromosomal aneuploidy and selective termination was performed. The parents also opted for this procedure in another five fetuses because of major structural abnormality diagnosed during NT assessment. No other chromosomal or major fetal abnormality were found post-natally. Although no difference was found in NT, crown-rump length and maternal age between spontaneous and assisted reproduction technology twin pregnancies, the former group had a significantly higher rate of screen-positive results (7 versus 2%, P = 0.047), amniocentesis uptake (33 versus 22%, P = 0.014), monochorionic twining (32 versus 4%, P = 0.001) and complicated pregnancy outcome (11 versus 5%, P = 0.02). CONCLUSION: The present study confirms that first trimester target scanning can improve outcome by early detection and management of cases with an anomalous co-twin. It also identifies some differences between spontaneously and artificially conceived twin pregnancies in relation to this area of testing.

Abortion, Induced↗
PubMed2004

Seeking more goodly creatures.

In principle, genetic and reproductive technologies might allow "enhanced" children--with mental aptitudes and personal qualities improved beyond their expected abilities or even beyond humanity's normal range. Worry about a "brave new world" has already begun, but is that world imminent? And assuming that parents could choose traits for their children, would this be a bad thing? Many people think so for many different reasons, Henry Greely writes, but before we decide to regulate genetic enhancement, we need to decide how it differs from other forms of enhancement, traditional and new, and if those differences are important enough to justify regulation.

Coercion↗
PubMed2002

Intentional parenthood: responsibilities in surrogate motherhood.

In recent years, a number of writers dealing with questions over parenthood that arise in the context of reproductive technologies and surrogate motherhood, have appealed to the notion of "intentional parenthood". Basing their argument on liberal values such as individual autonomy, the freedom to enter contracts, the right to privacy, and individual self-fulfilment, they argue that contractually stated intentions, rather than genetic or gestational relationships, should form the basis of parental rights. Against this I argue that parental rights do not derive from contractual agreements, but are based in their obligations towards the child. I then examine the nature of the obligations that the various parties have towards the child both pre- and postnatally.

Adoption↗