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Category Archives: Human Reproduction

Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation

BACKGROUND

Grafting of testicular tissue into immunodeficient mice has been used to differentiate the neonatal testes from different animal species up to the level of complete spermatogenesis; however, this approach has not been successful for human testicular tissue. The aim of this study was to evaluate the capacity for differentiation of infant human testicular tissue grafts.

METHODS AND RESULTS

Testicular tissue from a 3-month-old patient with testicular cancer was grafted into immunodeficient nude mice. At the time of grafting, A spermatogonia were the only germ cells present in the testicular tissue. B spermatogonia and first spermatocytes were observed at 7 months and 1 year after grafting, respectively. Positive immunostaining with antibodies against BOULE and CDC25A suggested that spermatocytes in the graft were not arrested but in meiosis. Furthermore, ultrastructural and immunohistochemical analyses showed that the onset of both Sertoli cell maturation and partial differentiation of Leydig cells preceded the appearance of spermatocytes. Differentiation of testicular cells was accelerated compared with in vivo development.

CONCLUSIONS

Spermatogenesis in the xenograft of infant human testicular tissues proceeded successfully from the stage of spermatogonial stem cells until pachytene spermatocyte formation. The differentiation of Sertoli cells and Leydig cells was reproduced in a manner similar to that in normal testicular development. Grafting of infant human testicular tissue may be a powerful tool to examine the early period of human spermatogenesis and may pave the way for fertility preservation among infant patients.

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Who should pay for assisted reproductive techniques? Answers from patients, professionals and the general public in Germany

BACKGROUND

Financing ART is variously regulated in the different countries of Europe. In Germany, coverage of assisted reproduction by statutory health insurances was restricted to 50% in 2004. We conducted a national survey among patients, professionals (physicians and other academics in IVF centres, psychosocial counsellors, medical ethicists, social lawyers, health politicians) and the general public in Germany regarding their opinions on financing ART.

METHODS

Standard questionnaire techniques (paper and pencil interviewing, computer-aided web interviewing, computer-aided telephone interviewing) were used.

RESULTS

The vast majority of all groups supported public coverage of ART. Co-payments by patients were considered appropriate by about one-third of the patients, two-third of the physicians and three quarters of all other groups. According to the respondents, the amount of co-payment should cover 15–25% of the costs, considerably less than what patients actually have to pay (50%). Support for public coverage was strongly correlated with the views (i) of infertility as a disease, (ii) that there is a need for assisted reproduction for infertile couples and (iii) that every human should have the opportunity to have children. The respondents had varying opinions on whether to increase medical insurance premiums in order to cover ART. Reducing services in other areas of health care in favour of reproductive medicine was supported only by the group of reproductive physicians. Financial incentives for oocyte sharing were rejected by most groups as was a money-back guarantee for unsuccessful treatments.

CONCLUSIONS

Experts and the general public in Germany accept moderate co-payments for ART. No clear pattern of opinion emerged regarding the question of how public co-funding should be financed.

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Avoidance of weekend oocyte retrievals during GnRH antagonist treatment by simple advancement or delay of hCG administration does not adversely affect IVF live birth outcomes

BACKGROUND

The use of GnRH antagonists in IVF treatment has many advantages over agonist long down-regulation, yet its uptake has been hampered by an inability to program the start date for gonadotrophin stimulation so as to minimize weekend oocyte retrievals (ORs). In this study, we retrospectively analyzed whether conducting a strict Monday to Friday OR program impacts on IVF outcomes.

METHODS

A total of 1642 non-programmed IVF antagonist cycles were analyzed to determine if advancing or delaying the OR by 1 day from ‘ideal’ to avoid Saturday or Sunday OR, respectively, had any impact on IVF outcomes. The IVF outcomes of Tuesday to Thursday served as a control as no modification in OR timing was required on these days.

RESULTS

Advancing the OR by 1 day from the ideal resulted in a small but significant decrease in the number of oocytes collected and embryos created. Delaying the OR by 1 day from ideal resulted in a small increase in the number of oocytes collected and embryos created. However, deviation from the ideal day of OR had no significant effect on live birth rates.

CONCLUSIONS

It is possible to safely avoid weekend ORs during GnRH antagonist cycles by simply advancing an ideal Saturday OR to Friday, and delaying an ideal Sunday OR to Monday, without adversely impacting on IVF live birth outcomes.

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Offering excess oocyte aspiration and vitrification to patients undergoing stimulated artificial insemination cycles can reduce the multiple pregnancy risk and accumulate oocytes for later use

BACKGROUND

The prevention of multiple pregnancies remains a major challenge in patients treated with ovarian stimulation prior to intrauterine insemination (IUI). The pilot study presented here investigates whether multiple pregnancies can be minimized by a microscopically confirmed aspiration of oocytes from supernumerary follicles immediately before intrauterine insemination and evaluates the benefit of concomitant excess oocyte cryopreservation for future use.

METHODS

Thirty-four aspirations of supernumerary follicles were performed immediately prior to IUI in 31 patients undergoing ovarian stimulation. sIUI was only performed if cumulus-oocyte complexes were microscopically observed in the aspirated follicular fluid. All collected mature excess oocytes were cryopreserved using the vitrification technique.

RESULTS

Only four sIUI procedures had to be cancelled due to failed oocyte retrieval or premature ovulation. IUI treatment resulted in a clinical pregnancy rate of 23.5% per cycle. All were singleton pregnancies. A total of 111 oocytes were cryopreserved. Patients with polycystic ovary syndrome (PCOS) had an average of 6.07 oocytes vitrified, whereas patients without PCOS had 1.3 oocytes vitrified per cycle.

CONCLUSION

Microscopically confirmed collection of excess oocytes prior to stimulated IUI reduced cancellation rates, further reduced the risk for multiple pregnancy and may lead to future additional pregnancies because, based on current information, approximately 5% of the vitrified oocytes could potentially establish a pregnancy.

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Pregnancy outcome in female childhood cancer survivors

BACKGROUND

The number of childhood cancer survivors has dramatically increased and consequently, an increasing number of survivors may now wish to conceive. Recently, several studies have described that previous treatment with abdominal radiotherapy may increase the risk of adverse pregnancy outcome.

METHODS

We conducted a retrospective single centre cohort study of childhood cancer survivors with a singleton live birth between January 2000 and December 2005. Pregnancy outcome was compared with data from the Netherlands Perinatal Registry, a nationwide database of pregnancy outcome parameters of all births in the Netherlands registered by midwives, obstetricians and paediatricians.

RESULTS

Data were available on 40 survivors and 9031 controls. Median age at diagnosis was 6.9 years (range 0.1–16.8 years). The median interval between diagnosis and date of delivery was 21.6 years (range 7.4–36.1 years). In the whole cohort, pregnancy outcome was not different between survivors and controls. However, survivors treated with abdominal radiotherapy delivered preterm and had post-partum haemorrhage (mean gestational age in survivors = 34.9 versus 39.2 weeks in controls, P = 0.001; 33% in survivors versus 5% in controls, P = 0.007, respectively). The offspring of survivors had normal birthweight after adjustment for gestational age (mean birthweight in offspring of survivors 2503 versus 1985 g; P = 0.22).

CONCLUSION

Childhood cancer survivors irradiated to the abdomen have an earlier delivery and higher incidence of post-partum haemorrhage. This stresses the need for close monitoring of the delivery, including inpatient perinatal care, in this group of childhood cancer survivors.

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Cumulative ongoing pregnancy rate achieved with oocyte vitrification and cleavage stage transfer without embryo selection in a standard infertility program

BACKGROUND

Recent advancement of minimum volume vitrification methods has resulted in a dramatic increase in the efficiency of the process. The aim of this study was to estimate the cumulative reproductive outcome of a cohort of infertile couples undergoing ICSI and oocyte vitrification in restrictive legal conditions, where only a limited number of oocytes could be inseminated per cycle and embryo selection and cryopreservation were forbidden.

METHODS

In this prospective longitudinal cohort study, the cumulative ongoing pregnancy rates obtained by the insemination of fresh and vitrified oocytes from the same cohort were calculated as primary outcome measures. Moreover, the effect of basal and cycle characteristics on clinical outcomes were assessed.

RESULTS

Between September 2008 and May 2009, 182 ICSI cycles were performed where oocyte vitrification was possible. A total of 104 first and 11 second oocyte warming cycles were then performed in non-pregnant patients of the same cohort. The overall ongoing pregnancy rates obtained in the fresh, and first and second warming cycles were 37.4, 25.0 and 27.3%, respectively. The overall cumulative ongoing clinical pregnancy rate observed per stimulation cycle was 53.3%. Maternal age was the only characteristic found to influence the reproductive outcome, with an inverse correlation between the age >40 and the ongoing pregnancy rates (P = 0.04, by Cox regression analysis).

CONCLUSIONS

High cumulative ongoing pregnancy rates can be obtained with transfers of embryos derived from fresh and cryopreserved oocytes in a typical infertile population. Female age significantly affects outcomes in this system.

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