First babies conceived with Automated Intracytoplasmic Sperm Injection.

RESEARCH QUESTION: Can an automated sperm injection robot perform Automated Intracytoplasmic Sperm Injection (ICSIA) for use in human IVF? DESIGN: The ICSIA robot automated the sperm injection procedure, including injection pipette advancement, zona pellucida and oolemma penetration with piezo pulses, and pipette removal after sperm release. The robot was first tested in mouse, hamster and rabbit oocytes, and subsequently using discarded human oocytes injected with microbeads. A small clinical pilot trial was conducted with donor oocytes to study the feasibility of the robot in a clinical setting. The ICSIA robot was controlled by engineers with no micromanipulation experience. Results were compared with those obtained with manual ICSI conducted by experienced embryologists. RESULTS: The ICSIA robot demonstrated similar results to the manual procedure in the different animal models tested as well as in the pre-clinical validations conducted in discarded human oocytes. In the clinical validation, 13 out of 14 oocytes injected with ICSIA fertilized correctly versus 16 out of 18 in the manual control; eight developed into good-quality blastocysts versus 12 in the manual control; and four were diagnosed as chromosomally normal versus 10 euploid in the manual control. Three euploid blastocysts from the ICSIA robot group have been transferred into two recipients, which resulted in two singleton pregnancies and two babies born. CONCLUSIONS: The ICSIA robot showed high proficiency in injecting animal and human oocytes when operated by inexperienced personnel. The preliminary results obtained in this first clinical pilot trial are within key performance indicators.

Mitochondrial DNA depletion in oocytes of HIV-infected antiretroviral-treated infertile women.

BACKGROUND: HIV-infected women under highly active antiretroviral therapy (HAART) undergoing in vitro fertilization (IVF) have a lower pregnancy rate than noninfected controls, which depends on oocyte-related factors. We hypothesized that mitochondrial toxicity caused by antiretrovirals could be the underlying mechanism of such disturbance. METHODS: We have studied 16 and 19 frozen-thawed oocytes obtained after oocyte retrieval IVF cycles from 8 and 14 infertile HIV-infected and uninfected women, respectively, matched by age. At inclusion, HIV-positive women had been infected for >13 years and had received HAART for >9 years, including at least one nucleoside reverse transcriptase inhibitor. All of them had undetectable HIV viral load and a good immunological status. Mitochondrial DNA (mtDNA) content was determined by quantitative real-time PCR in each individual oocyte. RESULTS: HIV-infected infertile women on HAART showed significant oocyte mtDNA depletion when compared with uninfected controls (32% mtDNA decrease, P<0.05). This oocyte mtDNA depletion was even greater on those HIV-infected women who failed to become pregnant when compared with controls (39% mtDNA decrease, P=0.03). No significant correlation was found between mtDNA oocyte content and cumulative doses of antiretrovirals or the immunological status of HIV patients. CONCLUSIONS: Oocytes from infertile HIV-infected HAART-treated women show decreased mtDNA content, and this could explain their poor reproductive outcome.

Lower endometrial receptivity in HIV-infected women receiving oocyte donation: a comorbidity of HIV infection?

STUDY QUESTION: Are the reproductive outcomes of HIV-infected donor oocyte recipient women comparable to those of non-infected women? SUMMARY ANSWER: HIV-infected women have lower clinical pregnancy and live birth rates than non-infected women. WHAT IS ALREADY KNOWN: The literature on the effect of HIV infection on reproductive outcome is scarce at best; the only report to date comparing oocyte donation cycles in HIV-infected women versus non-infected controls found no differences in pregnancy rates between the two groups. However, this study was performed nearly a decade ago and did not evaluate the effect of immuno-virological characteristics of oocyte recipients or the HIV antiretroviral therapy effect. STUDY DESIGN SIZE AND DURATION: This is a matched-cohort study including 514 oocyte donation cycles, 257 from HIV-infected women and 257 non-infected controls, performed between April 2004 and November 2014. PARTICIPANTS/MATERIALS SETTING AND METHOD: Each cycle of an HIV-infected woman (n = 257) was matched with a cycle of a non-infected woman (1:1). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy and live birth in the two groups were compared using a multivariate logistic regression analysis. The effect of antiretroviral treatment options on pregnancy outcomes of HIV-infected women was analyzed using a logistic regression model adjusted for time elapsed from diagnosis, and CD4 levels and viral load prior to embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Cycles of HIV-infected patients receiving oocyte donation presented lower pregnancy and live birth rates than matched non-infected controls. Treatment options and infection parameters analyzed do not seem to affect the reproductive results in HIV-infected women. The variable most influencing pregnancy outcomes was the number of transferred embryos; lower pregnancy rates were obtained after single embryo transfer. LIMITATIONS REASONS FOR CAUTION: Patients with HIV infection have specific health issues, such as infection/treatment side effects, which makes it impossible to find a matching control group of non-infected patients for these variables. WIDER IMPLICATIONS OF THE FINDINGS: HIV-infected women receiving donated oocytes present lower pregnancy rates when compared to non-infected controls, regardless of the antiretroviral treatment followed. The complexity of the treatments (both in medication types and combinations) makes it difficult to define whether any one treatment option is better than the others in terms of pregnancy outcomes in oocyte recipients. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Decreased pregnancy rate after in-vitro fertilization in HIV-infected women receiving HAART.

A study on in-vitro fertilization (IVF) was conducted among HIV-infected women. In these patients, a reduced pregnancy rate after IVF was observed if the patient's own oocytes were used. However, no significant reduction in the pregnancy rate was found if donated oocytes were used. The CD4 lymphocyte count was independently associated with ovarian resistance to hyperstimulation. Subclinical hypogonadism mediated by immunosuppression may explain these observations, suggesting the need to optimize the immunological status of the patient before considering assisted reproduction treatments.

Triggering with human chorionic gonadotropin or a gonadotropin-releasing hormone agonist in gonadotropin-releasing hormone antagonist-treated oocyte donor cycles: findings of a large retrospective cohort study.

OBJECTIVE: To compare pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) in donor stimulation cycles where final maturation of oocytes was induced with recombinant hCG or GnRH agonist. DESIGN: Retrospective, cohort study. SETTING: Private infertility clinic. PATIENT(S): A total of 1171 egg donors performing 2077 stimulation cycles. INTERVENTION(S): Controlled ovarian hyperstimulation of egg donors with GnRH antagonist protocol triggered with recombinant hCG (rhCG; 250 microg) or GnRH agonist (triptorelin 0.2 mg) based on the physician's decision. MAIN OUTCOME MEASURE(S): Proportion of mature and fertilized oocytes per donor cycle; clinical, ongoing pregnancy and implantation rate in recipients; and incidence of moderate/severe OHSS in oocyte donors. RESULT(S): The proportion of mature oocytes was comparable, whereas the difference in the fertilization rate reached statistical significance (65% vs. 69%). No significant differences were observed in the implantation rate or clinical and ongoing pregnancy rates per ET. The incidence of moderate/severe OHSS was 1.26% (13/1031; 95% confidence interval [CI], 0.74-2.15) and 0% (0/1046; 95% CI, 0.00-0.37) in the rhCG and GnRH agonist groups, respectively. CONCLUSION(S): Recipient outcome was not significantly different when using oocytes from GnRH antagonist-treated donor cycles triggered with hCG or GnRH agonist. However, GnRH agonist triggering was associated with a lower incidence of moderate/severe OHSS in egg donors.