Elisabet Clua

Elective single-embryo transfer in oocyte donation programmes: should it be the rule?

The aim of this study is to compare the cumulative clinical pregnancy and live birth rates (fresh embryo transfers followed by frozen-thawed embryo transfers from the same stimulated cycle) between single-embryo transfer (SET) and double-embryo transfer (DET) in an oocyte donation programme. A retrospective analysis of the outcome in 1139 recipient fresh cycles (1073 from DET and 66 from SET) with at least three available embryos for transfer was performed. The clinical pregnancy rates were similar after SET (45.5%, 30/66) and DET (57.1%, 613/1073), whereas the multiple pregnancy rate was 0% and 39.5% for SET and DET, respectively. After evaluating the results using the Kaplan-Meier survival analysis in a period of 1 year, no statistically significant differences were observed in the cumulative clinical pregnancy and live birth rates (SET 82.8% and 76.4% versus DET 77.2% and 63.7%). The results indicate that for women who have at least three available embryos in oocyte donation programmes, one single embryo should be transferred as no significant decrease in the success rate is observed and multiple pregnancy can be avoided. Clinical pregnancy rate is higher when transferring two embryos compared with one. However, this also results in a higher incidence of twin pregnancy, which is associated with increased obstetric and perinatal risks. The aim of this study was to compare the cumulative clinical pregnancy and live birth rates (fresh embryo transfers followed by frozen-thawed embryo transfers from the same stimulated cycle) between single-embryo transfer (SET) and double-embryo transfer (DET) cycles in our oocyte donation programme. A retrospective analysis of the outcome in 1139 recipient fresh cycles (1076 from DET and 66 from SET) with at least three available embryos for transfer was performed. The clinical pregnancy rates were similar after SET (45.5%, 30/66) and DET (57.1%, 613/1073), whereas the multiple pregnancy rate was 0% and 39.5% for SET and DET, respectively. The cumulative clinical pregnancy and live birth rates were similar between the two strategies (SET 82.8% versus DET 77.2%) and the same was found for the cumulative live birth rates (SET 76.4% versus DET 63.7%). Our results indicate that for women who have at least three available embryos in OD programmes, one single embryo should be transferred as no significant decrease in the success rate is observed while multiple pregnancy is avoided.

Identification and molecular cloning of two homologues of protein phosphatase X from Arabidopsis thaliana

In a recent paper [Ariño et al., Plant Mol Biol 21: 475–485 (1993)] we reported the amplification of a DNA fragment (AP-2) from the genome of Arabidopsis thaliana encoding an amino acid sequence corresponding to a Ser/Thr protein phosphatase distantly related to type 2A protein phosphatases. In this paper we report the use of the AP-2 fragment to isolate several cDNA clones from a leaf cDNA library. Two of these (EP 124 and Ep 129) largely overlap and contain the AP-2 sequence, whereas a third clone (EP 128) is different although very related in sequence (86% of identity). Clones EP 124/EP 129 and EP 128 were found to encode two highly related polypeptides (93% identity) of 305 residues, showing a very high identity (83%) to the catalytic subunit of protein phosphatase X (PPX) from rabbit. Therefore, they have been named PPX-1 (EP 124/EP 129) and PPX-2 (EP 128). Southern blot analysis of genomic DNA indicates that only these two genes encoding phosphatases closely related to PPX are present in the genome of A. thaliana. Both PPX-1 and PPX-2 are expressed at very low levels in A. thaliana flowers, leaves, stems and roots. The expression levels of four previously identified type 2A phosphatases are higher than those of PPX genes. PP2A-1 appears to be the major mRNA species detected in all the tissues analyzed.

Analysis of factors associated with multiple pregnancy in an oocyte donation programme

The aim of this study is to identify the factors associated with multiple pregnancy in an oocyte donation programme. A retrospective study (2000-2007) of 945 synchronous cycles was performed. Two embryos were transferred in all cycles on day 2 after oocyte retrieval. All variables (egg donor and recipient age, number of inseminated oocytes, fertilized oocytes, cleaved embryos, good-quality embryos available, good-quality embryos transferred and frozen embryos) were analysed in relation to the clinical pregnancy rate per transfer (PR) and the multiple pregnancy rate (MPR). The donor age was 26.8±4.5 years and recipient age was 41.0±5.4. The number of good-quality embryos per recipient was 3.1±2.5. The PR was 55.1% and the MPR 36.5%. The number of good-quality embryos transferred (2 versus 0) was significantly associated (P<0.05) with the PR (60.6% versus 43.5%). The relationship between the MPR and the number of good-quality embryos transferred was adjusted by donor and recipients age. For those patients who received 2 versus 0 good-quality embryos, the odds ratio of a multiple pregnancy was 2.1 (95% CI 1.121-3.876). The only predictive factor for multiple pregnancies in an oocyte donation programme is the quality of the transferred embryos. Since the development of assisted reproduction techniques, most countries have witnessed increased rates of multiple pregnancy. In IVF/intracytoplasmic sperm injection, effective strategies must be established to prevent multiple pregnancy without reducing overall pregnancy rates. In oocyte donation programmes, there is less awareness about the related risks. Actually, a minimum of two embryos are still transferred in most centres. The patients age is higher and this fact implies more obstetric and perinatal complications. The aim of this study is to identify the factors associated with multiple pregnancy to contribute to establish future guidelines to avoid those risks.

Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes

OBJECTIVE To assess the clinical pregnancy rate per transfer in recipients of embryos from donor oocytes obtained after ovarian stimulation initiated on day 2 (D2) or day 15 (D15) of the menstrual cycle with a secondary end point of comparing the response to stimulation. DESIGN Prospective observational comparative study. SETTING Private in vitro fertilization (IVF) program. PATIENT(S) Oocyte donors (OD) and recipients. INTERVENTION(S) Donors stimulated within 3 months, starting on day 2 or day 15 after bleeding, with recombinant follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH) antagonist, and GnRH agonist trigger, and oocytes vitrified and later assigned to recipients, followed by routine IVF procedures one to two embryos transferred. MAIN OUTCOME MEASURE(S) Primary outcome pregnancy rate, and secondary outcome number of mature oocytes retrieved. RESULT(S) Nine D2 and nine D15 cycles were performed in nine donors. There were no differences between D2 and D15 in the number of mature oocytes obtained (14.0±6.96 vs. 16.89±7.52). To date, 20 recipients have received vitrified oocytes (8 recipients received D2 oocytes and 12 recipients received D15 oocytes). There were no differences between the groups of recipients in fertilization rate (77.3% vs. 76.5%) or number of embryos transferred (1.50±0.53 vs. 1.67±0.65). Twelve clinical pregnancies were obtained. No differences were noted in pregnancy rates (62.5% vs. 58.3%) or implantation rates (41.67% vs. 45%) between recipients of D2 oocytes and recipients of D15 oocytes. CONCLUSION(S) Donor oocytes obtained after ovarian stimulation initiated on day 15 of the cycle achieve good pregnancy rates. This information is useful for patients with cancer undergoing fertility preservation. CLINICAL TRIAL REGISTRATION NUMBER NCT 01645241.

Heterotopic pregnancy in a cross border oocyte donation patient: the importance of cooperation between centers

OBJECTIVE To report a case of tubal heterotopic pregnancy after oocyte donation in a cross border patient. DESIGN Case report. SETTING Private University Clinic, Spain, and Public University Hospital, Italy. PATIENT(S) A woman with a tubal heterotopic pregnancy after oocyte donation. INTERVENTION(S) Oocyte donation and ET (Spain), laparoscopic removal of the tubal heterotopic pregnancy (Italy). MAIN OUTCOME MEASURE(S) Diagnosis and treatment of the heterotopic pregnancy. RESULT(S) Laparoscopic treatment of the heterotopic pregnancy resulting in a single ongoing intrauterine pregnancy. CONCLUSION(S) Cross border reproductive care is increasing in Europe. When patients go back to their respective countries of origin they may not inform their doctors about having undergone fertility treatments abroad. This can lead to a delayed diagnosis in case of complications arising after treatment or during pregnancy. It is of vital importance that clinicians are aware of this possibility to speed up the diagnosis and treatment of potentially fatal situations such as the one described in the present case report.

Prevention of prematurity by single embryo transfer

Abstract The development of assisted reproduction techniques (ART) represents an important advance in the treatment of human infertility. However, their great effectiveness has brought with it an excessive increase in multiple pregnancy rates with the serious medical, financial and social consequences that they entail. Now, the scientific societies, the health professionals, and the infertile couples themselves are aware of these risks and have worked together to implement various strategies to deal with this situation. The result that is being obtained from the strategy of selectively reducing the number of embryos transferred is obvious. The pandemic of multiple pregnancies is being brought under control and so we have effective prevention of the obstetric and neonatal complications arising from it. It is to be hoped that it will also contribute to significantly reducing the rates of prematurity and thus of severe neonatal complications.

Investigations into implantation failure in oocyte-donation recipients

In recent decades, the Western world has been experiencing a societal trend to prioritize the professional careers of women who postpone motherhood to about 40 years of age, when, unfortunately, natural reproductive potential declines. This is the reason why these women increasingly find it necessary to resort to oocyte donation to have a child. Thanks to the young age of the donors, the efficacy of oocyte donation is the highest of all assisted reproduction treatments and pregnancy rates achieved with this technique exceed 50%. Moreover, the large registries from ESHRE and ASRM show live birth rates close to this figure. However, there are patients who experience repeated failures in several oocyte-donation cycles, and so far oocyte-donation repeated implantation failure has not been clearly defined. This study analysed the results obtained from 2531 oocyte-donation cycles carried out in 1990 patients and defines oocyte-donation repeated implantation failure as failure to implant with more than two embryo transfers and more than four high-grade embryos transferred. This study observed this condition in 140 oocyte recipients (7%). Also, oocyte cohort size, uterine factors and systemic thrombophilias as important aetiological factors were identified were to offer new therapeutic strategies to patients.

Replacing GnRH agonists with GnRH antagonists in oocyte recipient cycle did not adversely affect the pregnancy rates

UNLABELLED The synchronization of the donor stimulation with the endometrial preparation of the recipient is usually done by downregulating the recipients pituitary with a GnRH analog. OBJECTIVE The aim of this study is to compare pregnancy and implantation rates among premenopausal oocyte recipients synchronized by pituitary suppression with GnRH agonist (Group AGO) or antagonist (Group ANTAG) and standard endometrial preparation with estrogen and gestagen. STUDY DESIGN Prospective, observational, transversal, comparative study. Consecutive recipients treated at Institut Universitari Dexeus between July 2008 and December 2009. RESULTS One hundred and eighty-three premenopausal women were included. No differences were found regarding the age of donors nor the age of recipients, fertilization rates, number of embryos transferred and embryo quality. No differences were found in clinical pregnancy rates (56.1% Group AGO vs. 52.4% Group ANTAG). CONCLUSION The administration of GnRH antagonists during endometrial preparation in oocyte recipients facilitates synchronization without affecting the pregnancy rate.

Is it justified to transfer two embryos in oocyte donation? A pilot randomized clinical trial

Multiple pregnancies involve high obstetric and perinatal risks. The aim of this study is to evaluate, in a pilot randomized control study, if the cumulative pregnancy and live birth rates of elective single embryo transfer (eSET) are comparable to the ones obtained with elective double embryo transfer (eDET). A total of 65 patients with at least two good quality embryos was randomized, 34 (52.3%) assigned to the eSET group and 31 (47.7%) to the eDET group. The cumulative pregnancy rates (eSET: 73.5% and eDET: 77.4%. RR: 0.95 95% CI: 0.72-1.25) and live birth rates (eSET: 58.8% and eDET: 61.3%. RR: 0.96 95% CI: 0.64-1.42) were similar in the two groups. The twin pregnancy rate in the fresh transfers of eDET group was 47.7% and 0% in the eSET group. The medical team decided to interrupt the study for reasons related to risks associated with elevated twin pregnancy rate, leaving low numbers of patients within the study as a result. When considering cumulative success rates, eSET and eDET are similar in terms of efficacy. However, eDET involves an increased and unacceptable twin pregnancy rate. The only prevention strategy is single embryo transfer.

Obstetric and perinatal complications in an oocyte donation programme. Is it time to limit the number of embryos to transfer

Abstract The aim of this study is to describe obstetric and perinatal complications in pregnancies from oocyte donation (OD) cycles, delivering in our centre and to determine the impact of maternal age. Retrospective observational study of a 225 singleton pregnancies, 113 multiple pregnancies and 447 live birth. Pearson’s χ2 test or Fisher’s exact test were used for the statistical analysis. A higher incidence of obstetric complications was observed in multiple compared to singleton pregnancies with regard to preeclampsia (24.8% versus 8%), premature rupture of membranes (9.7% versus 1.8%), preterm delivery at <37 weeks (54.9% versus 10.2%) and caesarean section (81.4% versus 64%) (p < 0.05). If the age factor is added, the caesarean sections are higher in the single pregnancy group aged ≥40 years than in the group of <40 years (73.5% versus 49.4%) (p < 0.05). A higher incidence is found in multiple versus singleton pregnancies for low birth weight (<2500 g) (61.1% versus 8.2%), admissions to the intensive care unit (15.2% versus 4.7%) and perinatal mortality (13.5‰ versus 0‰) (p < 0.05). It is necessary to consider preconception counselling prior to an OD cycle to inform patients about the incidence complications observed and recommend to transfer only a single embryo.