Oocyte cryopreservation following failed testicular sperm extraction: a French case report with implications for the management of non-obstructive azoospermia.

The French law regulating assisted reproductive technologies forbids donor spermatozoa to be available in case of failed testicular sperm extraction (TESE) performed on the day of oocyte retrieval. This article reports the first French live birth after intracytoplasmic sperm injection of donated spermatozoa into frozen-thawed oocytes cryopreserved following failure of TESE. By reinforcing the relevance of TESE performed on the day of oocyte retrieval, oocyte cryopreservation in couples having beforehand consented to go to sperm donation will avoid cycle cancellation and potentially lead to successful live birth. Therefore, it could modify the French policy of management of patients suffering from non-obstructive azoospermia.

Results and unsolved problems following the amendment to the Italian Law on assisted reproduction brought about by the Constitutional Court.

Since the approval of Law N° 40/2004, Italian specialists have been applying assisted reproductive techniques in compliance with a number of restrictions. Several attempts were made to find a solution to the practical and ethical issues brought about by this restrictive legislation. Finally, in May 2009, the Italian Constitutional Court banned most of the limitations. In the last year the authors worked together to study the impact of the Italian Constitutional Court modifications on assisted reproduction from both a gynecological and medico-legal point of view. Despite the clinically positive impact of the ruling, a lot of technical and legal unsolved issues still exist. Analyzing these problems, the authors stress the importance of a multidisciplinary approach to achieve adequate legislation in order to improve patients' outcome and avoid "reproductive migration" from Italy to other European Countries. New regulation could also be important for practitioners by keeping the risk of legal troubles to the minimum.

The 2004 Italian legislation on the application of assisted reproductive technology: epilogue.

OBJECTIVE: To evaluate how the unique Italian fertility regulations (≤3 inseminated oocytes/cycle, transfer of all embryos, prohibition of embryo cryopreservation) affected outcomes of ART. STUDY DESIGN: Case-control study from the Center of Reproductive Medicine, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. We compared outcomes of ART patients between five years before (n=1791) and five years after (n=2474) the implementation of the law. RESULTS: The mean embryo transfer (ET) rate was 3.1±2.1 and 1.7±1.1 before and after the law. Significantly more ICSI procedures were performed in women above 35 years old during the post-law period. The ET rate was higher before (88.6%) than after (80.5%) the law (OR 1.9, 95% CI 1.6, 2.2) especially in women >37 years undergoing ICSI (88.2 vs. 76.1%; OR 2.3, 95% CI 1.3, 4.2). The clinical pregnancy rates were practically unchanged but the proportion of triplet births significantly decreased after the law (10.3 vs. 4.1%, OR 2.7, 95% CI 1.4, 5.0). CONCLUSION: In contrast to interim analyses, we found that the statutory obligation to transfer all available embryos produced from up to three inseminated oocytes reduced the ET rates, especially in older women, and decreased the triplet births rate.

Contribution of cryopreservation in a mandatory SET policy: analysis of 5 years of application of law in an academic IVF center.

OBJECTIVE: To analyse treatment outcomes after SET law enforcement and to evaluate the contribution of cryopreservation in a SET policy. MATERIAL: Embryo transfer cycles performed after the law enforcement (SET period) was retrospectively compared to the cycles performed before the law enforcement (DET period). RESULTS: Pregnancy and delivery rates after fresh transfer of SET and DET periods were comparable (31.7% versus 33.3% and 24.5% versus 26.2%, respectively, NS). Overall twin delivery rate is significantly decreased after the law enforcement (11.3% versus 22.4%, p < 0.001) but not in patients aged 36 to 39 years (20.3% versus 24%, NS). Frozen-thawed embryo cycles allowed similar cumulative pregnancy rate (30.6%, NS). Taking into account all frozen embryos still to be transferred, SET period offers a better overall pregnancy rate than the DET period (36.1% versus 32.3%, p < 0.01). CONCLUSIONS: The Belgian law allowed a dramatic reduction of twin deliveries especially for patients under 39 years. Cryopreservation maintains a similar cumulative pregnancy rate.

Italian Constitutional Court modifications of a restrictive assisted reproduction technology law significantly improve pregnancy rate.

BACKGROUND: In May 2009, the Italian Constitutional Court banned most of the limitations of a restrictive law regulating assisted reproduction technology on the grounds that it limited a couple's right to have access to the best possible medical treatment and reduce any possible higher risk of complications. The aim of the study was to compare our results in fresh cycles before and after this change. MATERIALS AND METHODS: We analysed retrospectively 3274 IVF cycles: 2248 before and 1026 after the law was modified. RESULTS: There was no significant difference between the two groups in terms of age, basal FSH levels, years of infertility, the number of previous cycles or the number of oocytes retrieved but the number of oocytes used (2.7 ± 0.6 versus 4.6 ± 1.8; P = <0.001), the number of embryos obtained (2.0 ± 0.9 versus 3.3 ± 1.8; P = <0.001) and transferred (2.2 ± 0.7 versus 2.3 ± 0.7; P = <0.001) were all higher after the removal of the previous restrictions, as was the pregnancy rate per started cycle (23.49% versus 20.42%; P = 0.047). Before modification of the law, the pregnancies were single in 74.11% of the cases (versus 71.43% afterwards), twins in 23.44% (versus 26.89%; P = 0.318) and triplets in 2.46% (versus 1.68%; P = 0.594). CONCLUSIONS: Our preliminary results after the removal of the previous legal restrictions show a higher pregnancy rate per started cycle (3.7% represents a 15% difference) and a positive (albeit non-significant) trend towards a reduction in the number of multiple pregnancies.

The effect of the 2004 Italian law on outcomes of assisted reproduction technology in severe male factor infertility.

The Italian law regulating assisted reproductive technologies that came into force in 2004 restricts the number of fertilized oocytes per cycle to three, obliges the subsequent transfer of all resulting embryos and prohibits the freezing of surplus embryos. This study evaluates the impact of the law on severe oligozoospermic, cryptozoospermic, obstructive azoospermic and non-obstructive azoospermic patients. Intracytoplasmic sperm injection outcomes of 1066 cycles performed in the 4years before the passing of the law were compared with 804 cycles performed in the 4years after the law came to pass. Globally, analysis of clinical and obstetric outcomes showed a significant decrease in terms of pregnancy and delivery rates per cycle (17.8% versus 10.9% and 14.2% versus 8.5%, respectively) and per embryo transfer (18.8% versus 13.8% and 15.0% versus 10.7%, respectively), and a significant drop in multiple deliveries (35.1% versus 17.6%) in the post-law period. Cryptozoospermic and azoospermic couples were affected by the Italian law more than severe oligozoospermic couples. The results showed that the Italian law limits the efficiency of assisted reproduction treatment in couples with severe male factor. It is hoped that the Italian assisted reproductive technologies law is altered as soon as possible, allowing the insemination of more than three oocytes.

[Significance of reproductive medicine in regard to judicial and ethical concerns in Germany]. / Gesellschaftlicher Stellenwert und juristische Aspekte der Reproduktionsmedizin in Deutschland.

Reproductive medicine becomes more and more important due to demographic changes and an increased demand. Since the German "Embryonenschutzgesetz" was set in 1991 many medical improvements could be achieved which are not covered by law. Health can be improved avoiding multiple pregnancy rates. In Germany we are facing an insufficient law concerning reproductive medicine. Therefore, it is very important to renew the law in order to create a better health supply clearing crucial medical questions.

Egg freezing, procreative liberty, and ICSI: the double standards confronting elective self-donation of oocytes.

The consensus view among relevant professional societies opposing the offering of elective oocyte cryopreservation for potential future self-donation withstands neither clinical nor ethical scrutiny. The favorable risk-benefit ratio of this technology mandates both the prioritization of patient autonomy for informed women seeking to maximize-not guarantee-their chances of having genetically related children, and a justification for viewing egg freezing differently from intracytoplasmic sperm injection.

Selective microsurgical removal of a pronucleus from tripronuclear human oocytes to restore diploidy: disregarded but valuable?

OBJECTIVE: To review data on the microsurgical removal of a single pronucleus from tripronuclear human oocytes and evaluate the future potential of this technique for obtaining diploid, transferable embryos. DESIGN: Literature review. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Ten relevant studies were identified. These differ considering the removal technique itself, the application of cytoskeletal relaxants, and the survival rate after epronucleation. Diploidy and heteroparental inheritances could be confirmed in some preimplantation stages derived from epronucleated oocytes. Transfer of "corrected" embryos has been attempted only once, and resulted in a live birth. Noteworthy pitfalls associated with the procedure concern the exact identification of the supernumerary pronucleus, the presence of two centrosomes in dispermic oocytes, and cytogenetically abnormal pronuclear patterns after intracytoplasmic sperm injection. CONCLUSION(S): Patients with exclusively abnormally or few normally fertilized oocytes would profit from epronucleation to assure embryo transfer or increase the number of transferable embryos. Further research appears necessary and promising.

Fertility services for human immunodeficiency virus-positive patients: provider policy, practice, and perspectives.

OBJECTIVE: To examine demand for, and access to, fertility services for HIV-positive patients in the United States. DESIGN: An electronic survey. SETTING: The URL for the Web-based survey was e-mailed to those surveyed. PATIENT(S): The 916 members of the Society of Reproductive Endocrinology and Infertility of the American Society of Reproductive Medicine. MAIN OUTCOME MEASURE(S): Policy and practice in evaluation and treatment of HIV-positive and HIV-serodiscordant couples who desire conception, demand for services, and perceived barriers to providing these services. RESULT(S): The response rate was 22%. Forty percent of respondents reported policies. Fifty-one percent reported requests. Sixty-four percent reported offering treatment to HIV-serodiscordant couples, and 57% reported offering treatment to HIV-positive couples. Treatments most frequently offered to HIV-serodiscordant male-positive couples were reproductive surgery (50%), ovulation induction (46%), and intracytoplasmic sperm injection (45%). Twenty-nine percent of those offering treatment test-washed specimens for HIV. Factors limiting care included the following: low volume of requests (45%), concern for child welfare (37%), no laboratory policy (32%), and legal risk (32%). CONCLUSION(S): Patients who are HIV-positive are seeking fertility services in the United States. The small demand is a major limiting factor to provision of services. There is a lack of global application of current American Society of Reproductive Medicine guidelines. Provider education is needed to ensure that the safest reproductive services are offered to HIV-positive patients. Legal reform is imperative to improve access to reproductive services for the HIV-positive population.

Proposed ethical guidelines and legislative framework for permitting gestational surrogacy in Singapore.

Gestational surrogacy is currently banned in Singapore but is much debated. Some ethical guidelines and legislation for permitting gestational surrogacy in Singapore are proposed and discussed including: (i) review and approval of gestational surrogacy by the Ministry of Health on a case-by-case basis; (ii) stringent guidelines for gonadotrophin stimulation, IVF and ICSI procedures in 'traditional' surrogacy; (iii) restriction of gestational surrogates to parous married women with stable family relationships; (iv) exclusion of foreign women from acting as gestational surrogates, except for close relatives of the recipient couple; (v) reimbursement and/or compensation of gestational surrogates based on the direct expenses model; (vi) exclusion of medical professionals from surrogate recruitment and reimbursement; (vii) the surrogacy contract must make it legally binding for the prospective recipient couple to accept the child, even if it is born with congenital deformities; (viii) stringent guidelines for combining surrogacy with egg donation from a third woman, who is neither the social nor gestational mother. Policymakers in Singapore should conduct a public referendum on the legalization of gestational surrogacy and actively consult the views of healthcare professionals, religious and community leaders, as well as the general public, before reaching any decision.

A critical assessment of the impact of the European Union Tissues and Cells Directive (2004) on laboratory practices in assisted conception.

The European Union's Tissues and Cells Directive (2004) establishes an extensive framework of standards for all tissue banks throughout the EU. This article considers how the requirements of the Directive might be expected to achieve the stated goals of promoting the safety of assisted conception treatments and/or facilitating the achievement of higher success rates. While there will certainly be some significant costs to implementing these systems, there are substantial benefits and returns, for example, quality improvement and risk minimization. However, there are grave problems with the feasibility, effectiveness, and probable adverse impacts of applying arbitrary clean room air quality standards to assisted conception facilities, especially IVF laboratories. This is likely to have negligible impact on the already low risks of both culture contamination and operator infection, but would severely compromise the ability to maintain gametes and embryos under optimum environmental conditions. Proper consideration must therefore be given to the particular circumstances that affect reproductive tissues (indeed, the same is true for all areas of tissue banking), to ensure that the final technical regulations are founded upon realistic expectations based on objective evidence from process-based systems. The creation of the highest quality embryos, and healthy children, must always remain the primary focus of assisted conception treatment.

Outcome of ICSI in HIV-1-infected women.

BACKGROUND: Since 2001, French law has permitted the use of assisted reproductive technology in human immunodeficiency virus (HIV)-1 infected women under strict conditions. This report describes a preliminary series of seropositive women who underwent assisted reproduction treatment at our facility. To minimize contamination of culture media, equipment, and therefore of male gametes and embryos, we chose to perform ICSI in all cases. The outcome of ICSI was compared with the outcome in an age-matched group of non-HIV-1-infected women. Since several previous reports have indicated that HIV infection may be associated with a decrease in spontaneous fertility, our goal was also to assess the fertility status of the HIV-1-infected women entering our ICSI programme. METHODS: The French law governing the use of assisted reproduction protocols in HIV-1-infected women was strictly applied. The inclusion criteria were absence of ongoing disease, CD4((+)) count >200 cells/mm(3), and stable HIV-1 RNA level. Since mean age at the time of ICSI was higher in HIV-1-infected women than in the overall group of non-HIV-infected women, we compared outcome data in HIV-1-infected women (group I) to a group of non-HIV-1-infected women matched with regard to age and follicle retrieval period (group II) as well as to the overall group of women who underwent ICSI at our institution (group III). RESULTS: A total of 66 ovarian stimulations was performed in 29 HIV-1-infected-infected women. The percentage of cancelled cycles was higher in infected women than in matched controls (15.2 versus 4.9%, P < 0.05). The duration of ovarian stimulation (13.3 versus 11.7 days, P < 0.05) and amount of recombinant FSH injected (2898 versus 2429 IU, P < 0.001) were also higher in infected women. The number of retrieved oocytes, mature oocytes, and embryos obtained as well as embryo quality was similar in all groups. The fertilization rate was higher in infected women than in matched controls (67 versus 60%, P < 0.01). The pregnancy rate was not significantly different between groups I and II (16.1 versus 19.6%) in spite of the fact that the number of embryos transferred was purposefully restricted in the HIV-1-infected group to minimize multiple pregnancy (2.0 versus 2.4, not significant). CONCLUSION: The results of this preliminary series of ICSI cycles in HIV-1-infected women indicate that optimal ovarian stimulation is slightly more difficult to achieve than in matched seronegative women. However, when criteria for oocyte retrieval were fulfilled, ICSI results were similar to those of age-matched controls.

The 2004 Italian legislation regulating assisted reproduction technology: a multicentre survey on the results of IVF cycles.

BACKGROUND: The new Italian law, passed in 2004, regulating assisted reproduction technology imposes that no more than three oocytes can be fertilized at one time and that all embryos obtained must be transferred simultaneously. Oocyte cryopreservation is allowed while embryo cryostorage is banned. The aim of this study was to evaluate the clinical impact of these limitations. METHODS: Seven Italian infertility centres were invited to collect data on IVF cycles performed over the first 4 months of application of the new legislation. As a control, all centres provided data on cycles performed in the same solar period, 1 year before. RESULTS: Data from 1861 cycles were obtained, 961 in the pre-law period and 900 in the post-law period. Pregnancy rate per oocyte retrieval and rate of multiple pregnancies in the pre- and post-law periods were 27.0 and 24.2% (P=0.18) and 25.8 and 20.9% (P=0.11) respectively. However, the prohibition to freeze embryos does appear to have markedly reduced the cumulative rate of success. CONCLUSIONS: The rate of success of IVF-ICSI cycles using fresh embryos is not significantly influenced by the new legislation while the prohibition to freeze embryos seems to result in a more relevant impact.