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In vitro maturation of human oocytes.

Immature oocyte retrieval followed by in vitro maturation (IVM) opens a new horizon for modern assisted reproductive technologies (ART). Recent studies in IVM make it a feasible alternative to in vitro fertilization. Antral follicle count is correlated with the pregnancy rate, so women with polycystic ovarian syndrome or polycystic ovaries are the best candidates for IVM. IVM can also be offered to women at risk of ovarian hyperstimulation syndrome or poor responders. From the available information, IVM is a safe procedure and does not increase congenital anomalies or pregnancy complications. Further research is necessary in order to apply this technique to other patients.

Cells, Cultured↗

Escaping the tyranny of the embryo? A new approach to ART regulation based on UK and Australian experiences.

The early legislative responses to fertilization of human oocytes in vitro exaggerated the protection of the embryo at the expense of the interests of other parties. Although more recent legislative changes have lessened this embryonic grip, it nonetheless still distorts legal thinking and is fundamentally in conflict with biological understanding. Drawing largely on experiences in the UK and Australia, a proposal is explored that reframes the legislative approach to the regulation of assisted reproductive technology (ART) with the following objectives: (i) to align more closely the legal and biological understandings of the earliest stages of human development; (ii) to place the legislative focus on objective, intent and outcome; and in the process (iii) to disentangle legally and conceptually the status of the embryo from that of the potential child. Experiences in the UK and Australia are drawn on, because these two jurisdictions have a common legal heritage and were among the earliest players both scientifically and legally but have pursued very different legal routes to their current legislative practices.

Australia↗

[Clinical results of infertility treatment to male patients with spinal cord injury].

It is difficult for male patients with spinal cord injury (SCI) to have children because of an ejaculation and dysfunction of spermatogenesis. However, owing to progress of assisted reproduction technology in recent years, it has become possible to have children even if the male has SCI, and the rate of success is improving gradually. During the 8 years from 1994 to 2002, infertility treatment was performed on 16 male patients with SCI consulting our hospital for acquistion of a child. We extracted their sperm by electroejaculation (EE) or testicular excision sperm extraction (TESE), and the sperm was artificially inseminated by the techniques such as artificial insemination with husband's semen (AIH), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). Consequently, it was successful in 14 pregnancies on 10 couples, and resulted in 11 healthy live births on 7 couples. Four cases resulted in abortion. Two spouses are pregnant at present. There were no remarkable differences between the success group and the failure group in the quality of sperm such as concentration and motility. The mean age of the spouses who became pregnant was slightly lower than that of those who did not. Assisted reproduction techniques as EE and ICSI were useful techniques for patients with SCI wishing to have children.

Adult↗

A comparison of the ovarian response to external stimulation between women with right or left ovary participating in programs of ICSI/ET.

INTRODUCTION: Single ovary women compose a group of special interest in assisted reproduction technologies. The aim of the present study was to investigate whether the response to external stimulation and the outcome in women with a single ovary was affected by the location of the ovary. METHODS: Sixty cycles from 24 women, which stimulated with either hMG or rFSH and a GnRH agonist, were retrospectively studied. Twelve women had right and 12 had left ovary. In all cases, the fertilization was performed by intracytoplasmic sperm injection. RESULTS: There was not found any statistical significant difference between the two groups regarding the days of stimulation, the peak estradiol levels, the number of aspirated follicles, the number of retrieved oocytes, the fertilization rate and the number of transferred embryos. The cumulative embryo score (CES) was also similar in both groups. Six pregnancies in the group of the right ovary and seven in the group of left ovary were achieved. CONCLUSION: According to these results, right and left ovary, in single ovary women under external stimulation, are equally active and potent for reproduction.

Adult↗

Interrelationships between seminal parameters and sperm nuclear DNA damage before and after density gradient centrifugation: implications for assisted conception.

BACKGROUND: With an increase in the use of assisted reproduction technologies the requirements of the diagnostic semen analysis are constantly changing. METHODS: Spermatozoa from patients undergoing IVF were analysed by examining the conventional semen parameters and DNA/chromatin integrity, using in-situ nick translation (NT) and the Chromomycin A(3) fluorochrome, which indirectly demonstrates a decreased presence of protamine. Samples were examined before and after preparation using discontinuous density gradient centrifugation. RESULTS: Density gradient centrifugation enriched samples by improving the percentage of morphologically normal forms by 138% and sperm nuclear integrity by 450%. Sperm nuclear integrity as assessed by in-situ nick translation (NT) demonstrated a very clear relationship with sperm concentration, motility and morphology. Morphology correlated with fertilization rates of patients undergoing IVF, while NT values of the spermatozoa post-preparation were significantly lower in pregnant patients. CONCLUSIONS: We have demonstrated that along with the classical semen parameters, the assessment of nuclear integrity improves the characterization of the semen sample and may be used as a tool for allocating patients to specific assisted reproduction treatments.

Adult↗

Policy efforts to prevent ART-related preterm birth.

At 12.5%, the preterm birth rate is the highest it has ever been in the US. In tandem with the rise in preterm birth is a dramatic increase in multiple birth rates. The recent trend of delayed maternal age at first birth and the associated use of assisted reproductive technologies (ARTs) have led to the increase in multiple gestation and its attendant increased risk for preterm birth. While ARTs are not responsible for the majority of preterm births, the attributable fraction has increased, is iatrogenic- and preventable. Despite widespread recognition of this problem, the rate of associated twin gestation has not decreased. We offer options for policymakers on several levels--from medical to health systems to societal policy--to decrease ART-related preterm births.

Embryo Transfer↗

The role of ultrasonography in the evaluation of endometrial receptivity following assisted reproductive treatments: a critical review.

We set out to estimate the value of ultrasonographic parameters as prognostic indicators of implantation following in-vitro fertilization (IVF) and embryo transfer. Our survey included 414 natural cycles, 3558 cycles following ovarian stimulation for IVF and embryo transfer, and 411 cycles with hormone replacement therapy for oocyte donation, reviewing 27 reports identified in a computerized literature research. The ultrasonographic prognostic indicators for implantation evaluated included peri-ovulatory endometrial thickness and pattern and Doppler measurements of uterine artery blood flow. Topics include: definitions of the ultrasonographic parameters proposed to evaluate uterine receptivity; the clinical context in which they were used; the proposed optimal timing for sonographic evaluation; and, finally, their actual correlation with pregnancy rate following assisted reproductive technologies. For various sonographic parameters, negative predictive value, positive predictive value, sensitivity and specificity were calculated, based on published data. Sonographic parameters had a high negative predictive value and sensitivity, but a limited positive predictive value and low specificity. Several confounding factors may influence the interpretation of reports, and the statistical evaluation sometimes lacks calculation of the positive and negative predictive values of the parameters examined. Although ultrasonographic parameters of endometrial receptivity have a strong negative value in setting some minimum criteria, their value as prognostic indicators for implantation following embryo transfer has yet to be proved.

Embryo Implantation↗

A ray of light about frozen embryos.

The Tennessee Supreme Court's decision in Davis v. Davis, a case that raises the question of how to allocate frozen embryos in the event of divorce, addresses many of the legal issues posed by in vitro fertilization. The decision considers the interests of the progenitors as well as of the children who may result. For example, the court held that gamete providers' discretion regarding the disposition of embryos can be limited only when their decisions would harm the children who might be born. The court also made clear that efforts to seek genetic parenthood are protected only when accompanied by a desire to raise the resulting children, a conclusion that also affects other reproductive technologies. In addition to elaborating an analytic framework, the court set guidelines for resolving disputes when the couples had made no prior agreements, including holding that while the embryos are ex-utero the desire to avoid genetic parenthood almost always trumps the wish to become a parent. The well-reasoned analysis in Davis v. Davis should help shape legal and ethical discussion regarding the use of in vitro fertilization for many years to come.

Civil Rights↗

Aromatase inhibition for ovarian stimulation: future avenues for infertility management.

Ovarian stimulation is applied during infertility management either alone or in conjunction with intrauterine insemination and assisted reproductive technologies. At the present time, the two main medications used for ovarian stimulation include an oral antiestrogen, clomiphene citrate, and injectable gonadotropins. In spite of the high ovulation rate with the use of clomiphene citrate, the pregnancy rate is much lower. In clomiphene citrate failures, gonadotropin injections have generally been used as the next treatment option. Treatment with gonadotropins is difficult to control and characteristically associated with increased risk of severe ovarian hyperstimulation syndrome and high multiple pregnancies. Therefore, an effective oral treatment that could be used without risk of hyperstimulation and with minimal monitoring is the preferred therapy. We hypothesize that aromatase inhibitors can be administered early in the follicular phase to induce ovulation by releasing the hypothalamus or pituitary from estrogen negative feedback. Based on this hypothesis, we have reported the success of aromatase inhibitors in induction and augmentation of ovulation in addition to improving ovarian response to gonadotropin stimulation. Moreover, there are other potential applications for aromatase inhibitors in infertility management, including improving implantation in assisted reproduction and in-vitro maturation.

Anastrozole↗

Spare embryos: 3000 reasons to rethink the significance of genetic relatedness.

IVF laws in Victoria, Australia provide that human embryos must not remain in storage in excess of 5 years. Studies reviewing the fate of surplus human embryos reveal that close to 90% of couples choose to discard their excess embryos and that hundreds of embryos are disposed of annually. It has been argued that human embryos are a valuable resource and that there is a need to consider educational programmes to encourage couples to donate spare embryos to other infertile couples, rather than discard them. Surveys show that one reason that so few embryos are donated is that couples attach great significance to genetic parenthood. Advances in reproductive technology may necessitate a review of biological definitions of family and the importance of genetic relatedness. It can be argued that it is unreasonable to conclude that genetic ties are so significant that embryos should be discarded rather than donated and raised by non-genetically related parents. It is suggested that education programmes should encourage reflection on people's beliefs about the importance of genetic relatedness with regard to what makes a family. Open embryo donation or directed embryo donation programmes might cause couples to change their minds, or alleviate their anxiety about donating embryos to others.

Attitude↗

Rising multiple maternity rates and medical management of subfertility: better information is needed.

Multiple maternity rates rose rapidly from the mid-1970s onwards in many Western countries. This has major public heath implications, as multiple pregnancies can lead to many problems for the mothers and their children. Ovarian stimulation and assisted reproductive technology (ART) play a major role in these trends but there are few data about them. Consistently defined multiple maternity rates, including twin and triplet maternity rates are needed annually for each country in order to monitor time trends and make international comparisons. In order to assess the contribution of ovarian stimulation and ART to trends in multiple maternities and to monitor their impact on pregnancy outcome, fuller and more consistent data are needed. These could be collected from ART centres and other care providers, or through medical birth registries or national surveys.

Data Collection↗

Ovulatory failure, fertility preservation and reproductive strategies in the setting of gynecologic and non-gynecologic malignancies.

The advances in assisted reproductive technology over time have paralleled the insights gained into the natural history of different gynecologic malignancies. Subgroups of young patients with early stage ovarian cancer, endometrial carcinoma and cervical carcinoma may be considered to be at relatively low risk of recurrence and may be treated conservatively with the aim to preserve fertility when this is of prime concern. Unilateral adnexectomy with preservation of the contralateral ovary and uterus may be appropriate for some patients with epithelial ovarian cancers, and certainly should be the procedure of choice for those young women with borderline tumors and early stage sex cord-stromal and malignant germ cell tumors. Administration of high-dose progestins may obviate the need for immediate hysterectomy in a young patient with a well-differentiated endometrial carcinoma desirous of childbearing. The performance of vaginal radical trachelectomy in conjunction with laparoscopic pelvic lymphadenectomies has emerged as a real breakthrough for a highly select group of young women with early invasive tumors of the cervix. In this review, we also discuss reproductive strategies for women who experience chemotherapy-induced ovulatory failure and also address the potential for ovarian cortex cryopreservation and transplantation, and uterine transplantation, all of which are looming on the horizon.

Female↗

Application of assisted reproduction for population management in felids: the potential and reality for conservation of small cats.

Assisted reproductive technology (ART), using the primary applied tools of AI, ET, and sperm and embryo cryopreservation, has been promoted over the past decades for its potential to conserve endangered wildlife, including felids. However, if the goal is efficient, consistent production of viable offspring for population management, then the 'potential' of ART has yet to become 'reality' for any non-domestic cat species. For the five small-sized felids (i.e., Brazilian ocelot, fishing cat, Pallas' cat, Arabian sand cat, black-footed cat) managed by Species Survival Plans (SSPs) in North American zoos, achieving this potential may be an absolute necessity if genetically viable captive populations are to be maintained into the next century. Modeling programs suggest that current SSP populations are not sustainable without periodic introduction of new founders and improved demographic parameters, including longer generation intervals and larger population sizes. ART provides the means to address each of these management challenges. In each small cat SSP species, fecal hormone metabolite assays and seminal analysis have proven useful for characterizing basal reproductive parameters, a necessary prerequisite to developing ART. Of the five SSP species, ART has been used to produce living offspring only in the ocelot, including after AI with frozen-thawed spermatozoa and following transfer of frozen-thawed IVF embryos. The true efficacy of these techniques, however, is still unknown. To improve the applicability of ART for population management, priorities for immediate research include further investigation of ovarian stimulation protocols, sperm and embryo cryopreservation methods, embryo culture systems, and fetal and neonatal viability following ART.

Animals↗

Intrauterine insemination: a systematic review on determinants of success.

Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in infertility. Here, a systematic review of the literature was performed to examine the current status of clinical and laboratory methodologies used in IUI and the impact of female and male factors on pregnancy success. Emphasis was centred in questioning the following: (i) the value of IUI against timed intercourse; (ii) IUI application with or without controlled ovarian hyperstimulation; (iii) timing and frequency of IUI; and (iv) impact of various parameters (male/female) on the prediction of pregnancy outcome. The odds of multiple pregnancy occurrence and its risk factors, as well as the cost-effectiveness of IUI treatment compared with more complex assisted reproductive technologies are discussed. A computerized literature search was performed including Medline and the Cochrane library, as well as a crossover search from retrieved papers. It is concluded that although IUI is a successful contemporary treatment for appropriately selected cases of female and/or male infertility, further research is needed through well-designed studies to improve the methodologies currently utilized. Importantly, the clinical management of the infertile couple should be performed in an expedited manner taking into consideration the age of the woman, the presence of multifactorial infertility and cost-effectiveness of the available treatment alternatives.

Female↗

Embryo culture does not affect the longevity of offspring in mice.

The oldest assisted reproductive technologies (ART)-conceived child is only 27 years old. Thus, the effects of ART on longevity are unknown, and it will be many years before this can be assessed in humans. We recently reported that culturing preimplantation mouse embryos under suboptimal conditions results in differences in how the offspring perform in behavioral assays that reflect anxiety (elevated zero maze) and spatial memory (Morris hidden water maze; Ecker et al. 2004). Here we monitored the mice generated in our previous study and found no difference in their longevity.

Aging↗

Factors affecting the efficiency of embryo transfer in the domestic ferret (Mustela putorius furo).

Embryo transfer (ET) to recipient females is a foundational strategy for a number of assisted reproductive technologies, including cloning by somatic cell nuclear transfer. In an attempt to develop efficient ET in domestic ferrets, factors affecting development of transferred embryo were investigated. Unilateral and bilateral transfer of zygotes or blastocysts in the oviduct or uterus was evaluated in recipient nulliparous or primiparous females. Developing fetuses were collected from recipient animals 21 days post-copulation and examined. The percentage of fetal formation was different (P<0.05) for unilateral and bilateral transfer of zygotes (71%) in nulliparous females with bilateral transfer (56%) in primiparous recipients. The percentage (90%) of fetal formation in nulliparous recipients following unilateral transfer of blastocysts was higher (P<0.05) than that observed in primiparous recipients with bilateral ET (73%). Notably, the percentage of fetal formation was higher (P<0.05) when blastocyts were transferred as compared to zygotes (90% versus 71%). Transuterine migration of embryos occurred following all unilateral transfers and also in approximately 50% of bilateral transfers with different number of embryos in each uterine horn. These data will help to facilitate the development of assisted reproductive strategies in the ferret and could lead to the use of this species for modeling human disease and for conservation of the endangered Mustelidae species such as black-footed ferret and European mink.

Animals↗

[Psychosocial aspects of the direct path from infertility to the "instant family": are all risks known].

Infertility is invariably described as a crisis event. Couples who encounter infertility are further challenged with the accompanied sense of profound losses: loss of health, sexuality, status and prestige, relationship, self-confidence, self-esteem, security, and the fantasy for biological parenthood. Fertility treatments (ART) create hope and cure for the problem on one hand, but place a tremendous burden on the couple's resources on the other. Assisted Reproductive Technologies (ART), carry potential risks for both the infant and for the mother, in addition to diverse negative psychosocial consequences for the couple. However, it seems that couples either ignore these risks or are unaware of them, and therefore, wish to accomplish the "instant family" (more than one child) via a shortcut (one pregnancy). Although it is impossible to ignore the numerous children born with the aid of ART, it is crucial that professionals inform the couple about the medical as well as the psychological consequences that accompany fertility treatments, to enable couples to make more realistic decisions.

Family↗

Hypospadias after assisted reproduction incorporating in vitro fertilization and gamete intrafallopian transfer.

OBJECTIVE: To determine incidence of hypospadias in infants born as a result of assisted reproductive technology (ART). DESIGN: Prospective data collection. SETTING: Parents with various forms of infertility attended an in-hospital in vitro fertilization program. PATIENTS: Two of the 53 male infants, conceived as a result of ART over a 3-year period, were born with hypospadias. INTERVENTIONS: Patient no. 1 underwent follicular stimulation (17 ampules of human menopausal gonadotropin (hMG), followed by 10,000 IU of human chorionic gonadotropin (hCG) 60 hours after the last hMG). Patient no. 2 underwent follicular stimulation with clomiphene citrate 100 mg/d from days 3 to 7, followed by 14 ampules of hMG starting day 6, and 10,000 IU of hCG 30 hours after her last hMG. MAIN OUTCOME MEASURES: All infants were examined in the immediate postpartum period for congenital anomalies. RESULTS: Infant no. 1, one of a set of dizygotic twins, had penoscrotal hypospadias, with normal renal sonogram and chromosomal studies. Infant no. 2 had glandular hypospadias with the urinary meatus displaced to the border of the glans. CONCLUSION: This high incidence raises concern about possible links between assisted reproduction and hypospadias.

Adult↗