Javier Domingo

Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications

OBJECTIVE To evaluate the results of controlled ovarian hyperstimulation (COH) for oocyte vitrification to preserve fertility for medical and nonmedical indications. DESIGN A retrospective, multicenter, observational study performed between March 2007 and June 2012. SETTING University-affiliated infertility clinics. PATIENT(S) Of 560 nononcological patients and 475 oncological patients, we performed 1,080 oocyte vitrification cycles, 725 for nonmedical reasons and 355 in patients affected with cancer. Cycle outcome is presented, including 30 women who returned to use their frozen eggs with, 20 pregnancies obtained, 6 newborns, and 8 ongoing pregnancies. INTERVENTION(S) Controlled ovarian hyperstimulation, oocyte retrieval, warming of oocytes, and ET in those who already came back. MAIN OUTCOME MEASURE(S) Days of stimulation, total dose of gonadotropins, estrogen (E) and P levels, number of oocytes retrieved and vitrified, pregnancy rate (PR). RESULT(S) Comparable results were obtained in both groups of patients, with lower total dose of gonadotropins used and lower serum E(2) levels in patients affected with cancer. Frozen/thawed oocytes performed similarly in both groups. CONCLUSION(S) Patients who vitrify eggs for medical or nonmedical reasons perform similarly, as observed in this large series. This technique offers realistic expectations to both groups of patients to have a child with their own eggs. These data could be used to adequately counsel our patients.

Oocyte vitrification as an efficient option for elective fertility preservation

OBJECTIVE To provide a detailed description of the current oocyte vitrification status as a means of elective fertility preservation (EFP). DESIGN Retrospective observational multicenter study. SETTING Private university-affiliated center. PATIENT(S) A total of 1,468 women who underwent EFP because of age or having associated a medical condition other than cancer (January 2007 to April 2015). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Survival and cumulative live birth rate (CLBR) per consumed oocyte. RESULT(S) Mean age was higher with EFP due to age versus having an associated medical reason (37.7 y [95% confidence interval (CI) 36.5-37.9] vs. 35.7 y [95% CI 34.9-36.3]). In total, 137 patients (9.3%) returned to use their oocytes. Overall survival rate was 85.2% (95% CI 83.2-87.2). Live birth rate per patient was higher in women ≤35 years old than ≥36 years old (50% [95% CI 32.7-67.3] vs. 22.9% [95% CI 14.9-30.9]). CLBR was higher and increased faster in younger women. The gain in CLBR was sharp from 5 (15.4%, 95% CI -4.2 to 35.0) to 8 oocytes (40.8%, 95% CI 13.2-68.4), with an 8.4% gain per additional oocyte, in the ≤35-year-old group. The increase was slower with 10-15 oocytes, reaching a plateau CLBR of 85.2%. A milder increase (4.9% gain) was observed in the ≥36-year-old group (from 5.1% [95% CI -0.6 to 10.7] to 19.9% [95% CI 8.7-31.1] when 5-8 oocytes were consumed), reaching the plateau with 11 oocytes (CLBR 35.6%). Forty babies were born. CONCLUSION(S) At least 8-10 metaphase II oocytes are necessary to achieve reasonable success. Numbers should be individualized in women >36 years old. We suggest encouraging women who are motivated exclusively by a desire to postpone childbearing because of age, to come at younger ages to increase success possibilities.

Effect of different cryopreservation protocols on the metaphase II spindle in human oocytes

The aim of this study was to evaluate the impact of different cryopreservation protocols on the repolymerization of metaphase (M)II spindles in human oocytes. Fresh aspirated donor oocytes were cryopreserved 3-4 h after retrieval using four different protocols: slow freezing using 1.5 mol/l 1,2-propanediol (PROH) + 0.2 mol/l sucrose (n = 36); 1.5 mol/l PROH + 0.3 mol/l sucrose (n = 34); 1.5 mol/l PROH + 0.3 mol/l sucrose with Na(+) depleted-choline replaced media (n = 27), and vitrification by the Cryotip method (n = 23). The control group comprised 34 fresh oocytes. Three hours after thawing, surviving and control oocytes were fixed for meiotic spindle/chromatin assessment. Survival rates were 63.8, 73.5, 74.1 and 86.9% respectively for the four protocols described above. Survival for vitrified oocytes was higher than that observed for slow freezing with 0.2 and 0.3 mol/l sucrose (P < 0.05). The proportion of oocytes showing normal spindle configuration was similar for the four protocols (81, 73.9, 88.9 and 81.3% respectively) and 88.5% for controls, showing that the MII spindle returns to its normal configuration after 3 h of post-thawing incubation under standard conditions, irrespective of the cryopreservation technique used.

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.

Ovarian response to controlled ovarian hyperstimulation in cancer patients is diminished even before oncological treatment

OBJECTIVE To evaluate the results of controlled ovarian stimulation before chemotherapy for oocyte vitrification to preserve fertility in women diagnosed with cancer and compare them with a historical control group. DESIGN A retrospective, multicenter, observational study performed between March 2007 and January 2011. SETTING University-affiliated infertility clinics. PATIENT(S) Of 272 patients affected by cancer in our Fertility Preservation Program, 223 women underwent a stimulated cycle for oocyte vitrification according to our protocols before cancer treatment. Their results were compared with a historical control group of 98 patients diagnosed with male factor infertility who were stimulated for a conventional IVF cycle. INTERVENTION(S) Controlled ovarian stimulation and oocyte retrieval. MAIN OUTCOME MEASURE(S) Days of stimulation, total dose of gonadotropins, estrogen levels, and number of oocytes retrieved and vitrified. RESULT(S) No differences were found in days of stimulation, but significant differences in E(2) levels and the number of retrieved oocytes were measured, especially in the hormone-dependent cancer group. CONCLUSION(S) Patients with hormone-dependent cancer had a weaker response to controlled ovarian stimulation compared with patients with non-hormone-dependent cancer. Whether the oncological disease already affects the ovaries before chemo-/radiotherapy remains to be elucidated.

Obstetric outcome after oocyte vitrification and warming for fertility preservation in women with cancer.

Obstetric outcome of first pregnancies achieved after vitrification and warming oocytes from women being treated for cancer was evaluated. Of a total of 493 women who consulted for fertility preservation, 357 had their oocytes cryopreserved after being diagnosed with cancer, and 11 returned after being cured for assisted reproduction treatments (eight had breast cancer, one Hodgkin lymphoma, one endometrial adenocarcinoma, and one thyroid cancer). The oocyte survival rate was 92.3%, the fertilization rate was 76.6%, and the mean number of embryos transferred was 1.8 ± 0.7. Beta-human chorionic gonadotropin was detected in seven out of the 11 embryo transfers carried out. Four ongoing pregnancies were achieved and delivered at term with normal fetal weight and no major or minor malformations. Women diagnosed with cancer who have their eggs cryopreserved before anti-cancer treatment have good assisted reproductive technology performance and good perinatal outcomes. Cryopreservation of oocytes seems to be a good alternative for fertility preservation in these women.

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.

Los trastornos de la conducta alimentaria, consideraciones sobre nosología. etiopatogenia y tratamiento en el siglo XXI

Amazing advances have been made in medical sciences since the first international conference on eating disorders (ED) was held in the 1970s, and there have been remarkable changes in the field of ED itself. Back then, virtually all that was talked about was anorexia nervosa; clinicians and researchers were mainly concerned about the possible hypothalamic and endocrine factors that seemed to be involved and there had been no epidemiological studies or controlled trials with psychiatric drugs or psychotherapy. Although the picture today is quite different, there are still significant gaps which even affect the classification of these disorders, as well as their neurobiological bases and both the pharmacological and psychological treatments which should be used. This paper gives a brief summary of these gaps and discusses the need to find endophenotypes which may help in categorising and directing research into these disorders. Mention is made of possible contributions from other fields for the benefit of greater progress in understanding eating disorders. Specific reference is made to the addictive model, out of which neuropsychology and animal models may provide data transferable to our area of expertise. Lastly, the current state of ED treatment is discussed with pointers as to from what perspective it would be most useful to seek improvements.

Oocyte cryopreservation for fertility preservation in women with cancer

Purpose of reviewIt is necessary to clarify the fertility preservation-related points of concern that often frighten patients or physicians when it comes to deciding about oocyte cryopreservation for fertility preservation, which are often perceived as procedure limitations, are sometimes real and often theoretical and may make the prognosis worse. Recent findingsLetrozole added to gonadotrophins for controlled ovarian stimulation is safe when applied to hormone-sensitive cancer patients as it avoids associated high estradiol levels. This benefit is only for estrogens, but not for progesterone. Triggering ovulation with gonadotropin releasing hormone agonist bolus and adding the gonadotropin releasing hormone antagonist after oocyte retrieval help minimize its effect. A random start is currently widespread as neither results nor offspring are compromised, and it avoids waiting for menstruation and, therefore, delaying treatment. SummaryThe cumulative live birth rate is conditioned by the number of available oocytes and patients age. Assisted reproductive technologies may help cancer patients to achieve pregnancy with good obstetric outcomes and apparent oncological safety. Although counseling should be provided on an individual basis, fertility preservation in cancer patients and later pregnancy in survivors after adequate treatment and follow-up should not be discouraged.

The timing of administration of letrozole significantly affects the oocyte recovery rate in breast cancer patients undergoing controlled ovarian stimulation for fertility preservation

THE TIMING OF ADMINISTRATION OF LETROZOLE SIGNIFICANTLYAFFECTS THE OOCYTE RECOVERY RATE IN BREAST CANCER PATIENTS UNDERGOING CONTROLLED OVARIAN STIMULATION FOR FERTILITY PRESERVATION. C. Diaz-Garcia, J. Domingo, A. Romero, M. Martinez, J. M. Rubio, J. A. Garcia-Velasco, A. Pellicer. Woman’s Health Area, La Fe University Hospital, Valencia, Spain; IVI-Las Palmas, Las Palmas de Gran Canaria, Spain; IVIMadrid,Madrid, Spain; La Fe University Hospital, Valencia, Spain; IVI-Valencia, Valencia, Spain.