Juana Crespo

Twins born after transplantation of ovarian cortical tissue and oocyte vitrification

OBJECTIVE To present a combination of ovarian tissue and oocyte cryopreservation as an effective strategy for achieving pregnancy in a breast cancer patient. DESIGN Case report. SETTING Tertiary care university-affiliated hospital, tissue bank, and infertility clinic. PATIENT(S) A 36-year-old patient diagnosed with atypical medullar breast cancer and negative for estrogen, P, and HER2 receptors underwent ovarian tissue cryopreservation before receiving chemotherapy and radiotherapy. INTERVENTION(S) Laparoscopic ovarian cortex extraction, ovarian tissue cryopreservation, ovarian tissue thawing and transplantation, controlled ovarian stimulation (COS), oocyte retrieval, vitrification and IVF, and embryo culture and replacement. MAIN OUTCOME MEASURE(S) Resumption of spontaneous ovarian function after transplantation, response to COS, oocyte vitrification, IVF, pregnancy, and delivery. RESULT(S) Menses occurred 63 days after transplantation. Sixteen mature oocytes were obtained in four COS procedures. All vitrified oocytes survived warming, and 77.7% were fertilized. Two day 3 embryos were replaced, and two healthy boys were born at 34 weeks. CONCLUSION(S) Ovarian tissue cryopreservation and grafting preserves fertility. Simultaneous oocyte vitrification increases the success of assisted reproductive technology in poor-prognosis patients and avoids the consequences of the short lifespan of the transplanted tissue.

Accumulation of oocytes: a new strategy for managing low-responder patients

Accumulation of oocytes from several ovarian stimulation cycles is currently possible using novel vitrification technologies. This strategy could increase the inseminated cohort, creating a similar situation to normoresponders. This study included 242 low-responder (LR) patients (594 cycles) whose mature oocytes were accumulated by vitrification and inseminated simultaneously (LR-Accu-Vit) and 482 patients (588 cycles) undergoing IVF/embryo transfer with fresh oocytes in each stimulation cycle (LR-fresh). Drop-out rate in the LR-fresh group was >75%. The embryo-transfer cancellation per patient was significantly lower in the LR-Accu-Vit group (9.1%) than the LR-fresh group (34.0%). Live-birth rate (LBR)/patient was higher in the LR-Accu-Vit group (30.2%) than the LR-fresh group (22.4%). Cumulative LBR/patient was statistically higher in the LR-Accu-Vit group (36.4%) than the LR-fresh group (23.7%) and a similar outcome was observed among patients aged ⩾40years (LR-Accu-Vit 15.8% versus LR-fresh 7.1%). The LR-Accu-Vit group had more cycles with embryo cryopreservation (LR-Accu-Vit 28.9% versus LR-fresh 8.7%). Accumulation of oocytes by vitrification and simultaneous insemination represents a successful alternative for LR patients, yielding comparable success rates to those in normoresponders and avoiding adverse effects of a low response. The accumulation of oocytes from several ovarian stimulation cycles is currently possible with the aid of novel vitrification technologies. This strategy could be useful for low-responder patients, contributing to increase the inseminated cohort and creating a similar situation as in normal responders. According to the results presented herein (higher live-birth rate per patient treated), this strategy represents a successful alternative for low-responder patients, yielding comparable success rates to those in normal responders and avoiding the adverse effects of a low response.

Implications of sperm chromosome abnormalities in recurrent miscarriage

Purpose:Our purpose was to assess the existence of sperm chromosome abnormalities in recurrent pregnancy loss in an assisted reproduction program.Methods:In this prospective study, 12 sperm samples from couples undergoing in vitro fertilization with two or more first-trimester spontaneous abortions were analyzed. Diploidy and disomy in decondensed sperm nuclei were assessed for chromosomes 13, 18, 21, X, and Y using two- and three-color fluorescence in situ hybridization.Results:Sex chromosome disomy in sperm samples from recurrent abortion couples was significantly increased compared to that from internal controls (0.84% vs 0.37%). In a subpopulation of seven couples who underwent oocyte donation, mean frequencies for sex chromosome disomy (1%) were even higher and diploidy (0.43%) was also significantly increased.Conclusions:These results suggest an implication of sperm chromosome abnormalities in some cases of recurrent pregnancy loss.

New options in assisted reproduction technology: the Cryotop method of oocyte vitrification

The Cryotop vitrification method has been shown to be a very useful tool for oocyte cryopreservation, giving excellent results regarding survival and clinical outcome. There are several clinical situations in which oocyte cryopreservation provides solutions that have not been available to date. This report describes three of these situations: (i) a low-responder patient who needed a single gene diagnosis due to the presence of a genetic disease; (ii) a patient undergoing endometrial bleeding on the day of oocyte retrieval who was also affected by a genetic disorder; and (iii) a patient who failed to become pregnant after the donation of vitrified oocytes and subsequently had the re-vitrified surplus embryos transferred. The resolution of these cases provides evidence of the enormous potential of the Cryotop method as a tool within assisted reproduction technology.

Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis

OBJECTIVE To analyze the impact of LH administration on cycle outcome in ovarian stimulation with GnRH antagonists. DESIGN Randomized, open-label, controlled trial performed in two age subgroups. Recombinant (r) FSH versus rFSH + rLH administration was compared. SETTING University-affiliated private infertility clinic. PATIENT(S) Up to 35 years old (n = 380) and aged 36 to 39 years (n = 340), undergoing their first or second IVF cycle. INTERVENTION(S) Recombinant LH administration since stimulation day 1. MAIN OUTCOME MEASURE(S) Implantation rate, ongoing pregnancy rate. RESULT(S) In the young population, implantation rates were similar: 27.8% versus 28.6%, odds ratio (OR) 1.03 (95% confidence interval [CI] 0.73-1.47), as was the ongoing pregnancy rate per started cycle: 37.4% versus 37.4%, OR 1.0 (95% CI 0.66-1.52). In older patients, the implantation rate was significantly higher in the rFSH + rLH group: 26.7% versus 18.6%, OR 1.56 (95% CI 1.04-2.33). Ongoing pregnancy rates per started cycle were 33.5% versus 25.3%, OR 1.49 (95% CI 0.93-2.38). CONCLUSION(S) Recombinant LH administration significantly increased the implantation rate in patients aged 36 to 39 years. A clinically relevant better ongoing pregnancy rate per started cycle was observed, although the difference was not statistically significant. Patients younger than 36 years do not obtain any benefit from rLH administration.

The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: is it hypoandrogenic?

STUDY QUESTION What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? SUMMARY ANSWER Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. WHAT IS KNOWN ALREADY Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. STUDY DESIGN, SIZE AND DURATION A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E₂), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed. MAIN RESULTS AND THE ROLE OF CHANCE Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology. LIMITATIONS, REASONS FOR CAUTION The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power. WIDER IMPLICATIONS OF THE FINDINGS This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long-interval androgen priming to potentially increase the recruitment of small antral follicles rather than increasing the intraovarian androgen levels within the current cycle. STUDY FUNDING/COMPETING INTEREST The present project has been supported by the R+D programme from the Generalitat Valenciana (Regional Valencian Government) IMPIVA MIDTF/2010/95. The authors have no conflict of interest to declare.

New approaches to female fertility preservation

Survival rates have been improved in young cancer patients due to advances in oncologic treatments. It is necessary to focus on the consequences of cancer treatments and try to elude or at least prevent them. Menopause and infertility are two of the main causes for concern to those patients who survive cancer. When a solution is offered to these patients, their quality of life and self-esteem can be dramatically increased after therapy. Results observed in vitrified oocytes are similar to those achieved with fresh oocytes, giving this method great potential. Recommendations on fertility preservation should be focused on the oocyte vitrification method, which should be considered as the first option. Limitations of this approach are the need for ovarian stimulation, which means a 2–3 week period prior to chemotherapy and the possibility of high oestradiol levels when tumours are hormone dependent.