Replacing HMG/FSH by low-dose HCG to complete corifollitropin alfa stimulation reduces cost per clinical pregnancy: a randomized pragmatic trial.

RESEARCH QUESTION: The cost of IVF treatment remains high, among other factors because of the medication needed for ovarian stimulation. This study investigated the effect of using low-dose human chorionic gonadotrophin (HCG) for the second phase of follicular maturation after corifollitropin alfa induction, to replace the more expensive, either recombinant or human menopausal gonadotrophin (HMG), on the cost of ovarian stimulation. DESIGN: One hundred and five patients were randomly divided into two groups: patients in the HCG group (n = 50) received low-dose HCG from Day 7 until the diameter of at least three follicles reached 17 mm or more, while patients in the FSH group (n = 55) received conventional ovarian stimulation with highly purified HMG injections. RESULTS: The clinical pregnancy rate in the HCG group was 38% higher than in the FSH group (number needed to treat, NNT = 13). The cost per pregnancy needed for ovarian stimulation was reduced from €4902 in the FSH group to €2684 in the HCG group. Hence, the cost of ovarian stimulation medication to obtain 10 pregnancies using the conventional FSH protocol is sufficient to attain 18 pregnancies when applying the low-dose HCG protocol. CONCLUSION: This study provides evidence that using HCG instead of HMG/FSH for ovarian stimulation results in a significant reduction in the cost of IVF with, at least, an equivalent pregnancy rate.

Forty years of IVF.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.

No need for luteal phase support in IVF cycles after mild stimulation: proof-of-concept study.

This is a pilot study performed in a private IVF unit. The objective of the study was to investigate whether luteal support is required in IVF cycles after mild stimulation with clomiphene citrate and low FSH doses. The study included 15 patients with good prognosis (defined as ≤38 years old with normal ovarian reserve and normovulatory cycles, body mass index <29 kg/m2, no previous cycles, no severe endometriosis, no history of recurrent miscarriage, no endocrine/autoimmune diseases and no surgical semen extraction from the partner) undergoing IVF with mild stimulation. Patients were monitored during the luteal phase by serum progesterone and LH. The luteal support was started only when necessary. No patient needed luteal phase support because the resultant steroid environment was different from that associated with conventional stimulation techniques. The live birth rate was 40% (6/15) and the implantation rate 30% (6/20). There are several benefits to mild stimulation, including low cost, less patient distress and improved endometrial receptivity. Our study supports the concept that mild stimulation may have an additional benefit during the luteal phase, by obviating the need for luteal phase support.

Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.

STUDY QUESTION: What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels? SUMMARY ANSWER: The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm. WHAT IS KNOWN ALREADY: In comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol. STUDY DESIGN, SIZE, DURATION: From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a combination of both, were determined. MAIN RESULTS AND THE ROLE OF CHANCE: The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins. WIDER IMPLICATIONS OF THE FINDINGS: For patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00702845 NCT00696800 NCT00696878.

Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.

In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).

Mild ovarian stimulation with clomiphene citrate launch is a realistic option for in vitro fertilization.

OBJECTIVE: To validate the use of clomiphene citrate in IVF when mild stimulation approaches are chosen to reduce patient discomfort, risk, and cost. DESIGN: Prospective cohort study. SETTING: Private IVF clinic. PATIENT(S): A total of 163 patients undergoing IVF and with a good prognosis (defined as ≤38 years old with normal ovarian reserve and normovulatory cycles, body mass index <29 kg/m(2), no previous assisted reproductive technology cycles, no severe endometriosis, no history of recurrent miscarriage, no endocrine/autoimmune diseases, and no surgical semen extraction). INTERVENTION(S): Mild stimulation using a fixed protocol of clomiphene citrate (100 mg/d from cycle days 3 to 7) in combination with low doses of gonadotropins (150 IU of recombinant FSH on cycle days 5, 7, and 9) and GnRH antagonist. MAIN OUTCOME MEASURE(S): The cumulative delivery rate per patient after three fresh and/or frozen embryo transfers and time to pregnancy. RESULT(S): No dropouts were observed. The cumulative delivery rate was 70%, and the mean time to pregnancy was 2.4 months. CONCLUSION(S): Mild stimulation using clomiphene citrate in combination with low doses of gonadotropins can be considered a realistic option for good-prognosis patients undergoing IVF.

Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology--assisted reproduction technology.

A substantial body of research on mammalian gametogenesis and human reproduction has recently investigated the effect of myo-inositol (MyoIns) on oocyte and sperm cell quality, due to its possible application to medically assisted reproduction. With a growing number of both clinical and basic research papers, the meaning of several observations now needs to be interpreted under a solid and rigorous physiological framework. The 2013 Florence International Consensus Conference on Myo- and D-chiro-inositol in obstetrics and gynecology has answered a number of research questions concerning the use of the two stereoisomers in assisted reproductive technologies. Available clinical trials and studies on the physiological and pharmacological effects of these molecules have been surveyed. Specifically, the physiological involvement of MyoIns in oocyte maturation and sperm cell functions has been discussed, providing an answer to the following questions: (1) Are inositols physiologically involved in oocyte maturation? (2) Are inositols involved in the physiology of spermatozoa function? (3) Is treatment with inositols helpful within assisted reproduction technology cycles? (4) Are there any differences in clinical efficacy between MyoIns and D-chiro-inositol? The conclusions of this Conference, drawn depending on expert panel opinions and shared with all the participants, are summarized in this review paper.

International Federation of Fertility Societies Surveillance 2013: preface and conclusions.

Surveillance is a triennial worldwide compendium of national rules and regulations for assisted reproductive technology. It was last published in 2010.

Severe ovarian hyperstimulation syndrome after gonadotropin-releasing hormone (GnRH) agonist trigger and "freeze-all" approach in GnRH antagonist protocol.

OBJECTIVE: To report two cases with GnRH agonist triggering and a freeze-all approach in a GnRH antagonist protocol resulting in the development of severe ovarian hyperstimulation syndrome (OHSS), requiring hospitalization and peritoneal drainage. DESIGN: Two case reports. SETTING: A tertiary referral center and an obstetrics and gynecology department of a hospital. PATIENT(S): Case 1 and case 2: severe OHSS with abdominal distension, ascites development, and hemoconcentration. INTERVENTION(S): Case 1 and case 2: diagnosed by clinical, hematologic, and ultrasound findings. Hospitalization, IV infusion, and peritoneal drainage. MAIN OUTCOME MEASURE(S): Symptomatic treatment and prevention of further complication. RESULT(S): Complete recovery. CONCLUSION(S): Two cases of severe OHSS after GnRH agonist trigger in a GnRH antagonist protocol without the administration of any hCG for luteal-phase support. Clinicians have to be aware that even the sequential approach to ovarian stimulation with a freeze-all attitude does not completely eliminate OHSS in all patients.

Slightly lower incidence of ectopic pregnancies in frozen embryo transfer cycles versus fresh in vitro fertilization-embryo transfer cycles: a retrospective cohort study.

OBJECTIVE: To analyze the incidence of ectopic pregnancies (EPs) in fresh and frozen/thawed cycles. DESIGN: A retrospective cohort study on the incidence of EPs in all fresh IVF cycles from January 2002 until December 2012. This was compared with the incidence of tubal pregnancies in patients undergoing transfer of frozen/thawed embryos during the same time period. SETTING: The IVF program at Fertility Center, AZ Jan Palfijn, Gent, Belgium. PATIENT(S): A total of 11,831 patients undergoing IVF (i.e., the entire population of the IVF Center) were retrospectively analyzed. INTERVENTION(S): The IVF cycles, fresh IVF-ET, frozen/thawed ET. Laparoscopy for treatment of EP. MAIN OUTCOME MEASURE(S): Primary end point: incidence of EPs in both groups. Secondary end points: clinical pregnancy rate (PR), rate of EPs per clinical pregnancy. RESULT(S): In the fresh IVF cycle group, 10,046 patients underwent oocyte retrieval; 9,174 of them had an ET; 2,243 of these patients had a clinical pregnancy. Of these, 43 (0.47%) appeared to have an ectopic localization of their pregnancy. In the group of the patients undergoing frozen/thawed ET (1,785 patients) there were 467 pregnancies and 6 ectopic implants (0.34%). The incidence of the EPs per established clinical pregnancy was 1.92% for the fresh vs. 1.28% for the frozen/thawed cycles. CONCLUSION(S): No significant difference could be demonstrated on the incidence of EP in fresh IVF cycles vs. frozen/thawed cycles in a large cohort of patients.

Corifollitropin alfa or rFSH treatment flexibility options for controlled ovarian stimulation: a post hoc analysis of the Engage trial.

BACKGROUND: We sought to determine the impact of treatment flexibility on clinical outcomes in either a corifollitropin alfa or recombinant follicle-stimulating hormone (rFSH) protocol. METHODS: Post hoc analysis of a prospective, multicenter, randomized, double-blind, double-dummy non-inferiority clinical trial (Engage). Efficacy outcomes were assessed on patients from the Engage trial who started treatment on menstrual cycle day 2 versus menstrual cycle day 3, patients who received rFSH step-down or fixed-dose rFSH, patients who received rFSH on the day of human chorionic gonadotropin (hCG) compared with those who did not, and patients who received hCG when the criterion was reached versus those with a 1-day delay. RESULTS: The effect of each of the treatment flexibility options on ongoing pregnancy rate was not significant. The estimated difference (95% confidence interval) in ongoing pregnancy rate was -4.3% (-9.4%, 0.8%) for patients who started ovarian stimulation on cycle day 2 versus day 3, 1.8% (-4.1%, 7.6%) for patients who received hCG on the day the hCG criterion was met versus 1 day after, 3.2% (-2.1%, 8.6%) for patients who received rFSH on the day of hCG administration versus those who did not, and -5.8% (-13.0%, 1.4%) for patients who received a reduced versus fixed-dose of rFSH from day 8. CONCLUSIONS: Treatment flexibility of ovarian stimulation does not substantially affect the clinical outcome in patients' treatment following initiation of ovarian stimulation with either corifollitropin alfa or with daily rFSH in a gonadotropin-releasing hormone antagonist protocol. TRIAL REGISTRATION: Trial was registered under ClinicalTrials.gov identifier NCT00696800.

Low tolerance for complications.

Assisted reproductive techniques can lead to medical complications such as multiple pregnancy and ovarian hyperstimulation syndrome. A critical appraisal and strategies to reduce the occurrence of these complications are discussed in this manuscript.

Pregnancy prediction in single embryo transfer cycles after ICSI using QPCR: validation in oocytes from the same cohort.

Cumulus cell (CC) gene expression is being explored as an additional method to morphological scoring to choose the embryo with the highest chance to pregnancy. In 47 ICSI patients with single embryo transfer (SET), from which individual CC samples had been stored, 12 genes using QPCR were retrospectively analyzed. The CC samples were at the same occasion also used to validate a previously obtained pregnancy prediction model comprising three genes (ephrin-B2 (EFNB2), calcium/calmodulin-dependent protein kinase ID, stanniocalcin 1). Latter validation yielded a correct pregnant/non-pregnant classification in 72% of the samples. Subsequently, 9 new genes were analyzed on the same samples and new prediction models were built. Out of the 12 genes analyzed a combination of the best predictive genes was obtained by stepwise multiple regression. One model retained EFNB2 in combination with glutathione S-transferase alpha 3 and 4, progesterone receptor and glutathione peroxidase 3, resulting in 93% correct predictions when 3 patient and treatment cycle characteristics were included into the model. This large patient group allowed to do an intra-patient analysis for 7 patients, an analysis mimicking the methodology that would ultimately be used in clinical routine. CC related to a SET that did not give pregnancy and CC related to their subsequent frozen/thawed embryos which ended in pregnancy were analyzed. The models obtained in the between-patient analysis were used to rank the oocytes within-patients for their chance to pregnancy and resulted in 86% of correct predictions. In conclusion, prediction models built on selected quantified transcripts in CC might help in the decision making process which is currently only based on subjective embryo morphology scoring. The validity of our current models for routine application still need prospective assessment in a larger and more diverse patient population allowing intra-patient analysis.

Does the time interval between antimüllerian hormone serum sampling and initiation of ovarian stimulation affect its predictive ability in in vitro fertilization-intracytoplasmic sperm injection cycles with a gonadotropin-releasing hormone antagonist? A retrospective single-center study.

OBJECTIVE: To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response. DESIGN: Retrospective cohort study. SETTING: University-based tertiary center. PATIENT(S): Five hundred and forty women with AMH values measured before their first IVF-ICSI cycle. INTERVENTION(S): Eligible patients treated with 150-225 IU recombinant follicle-stimulating hormone (FSH) in a gonadotropin-releasing hormone (GnRH) antagonist protocol. MAIN OUTCOME MEASURE(S): Predictive ability of AMH for low and excessive ovarian response in relation to the time interval between serum AMH sampling and initiation of ovarian stimulation for IVF-ICSI. RESULT(S): All patients had their AMH concentration measured up to 12 months before initiation of stimulation. The level of AMH demonstrated a statistically significant positive correlation with number of oocytes retrieved. The time interval between AMH measurement and initiation of stimulation had no influence on this correlation. The area under the receiver operator characteristic curve (ROC AUC) of AMH was high for both poor (0.72) and excessive response (0.80). The ROC regression analysis demonstrated that the time interval from sampling did not affect the performance of either poor response or excessive response prediction. CONCLUSION(S): A time interval up to 12 months between AMH serum sampling and initiation of ovarian stimulation does not appear to affect the correlation between AMH level and the number of oocytes retrieved and the predictive ability of AMH to identify women at risk of low or excessive ovarian response.

Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients: an observational pilot study.

OBJECTIVE: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. DESIGN: Retrospective pilot study. SETTING: University-based tertiary care center. PATIENT(S): Poor ovarian responders fulfilling the Bologna criteria developed by European Society for Human Reproduction and Embryology Consensus Group. INTERVENTION(S): Corifollitropin alfa (150 µg) followed by 300 IU rFSH in a GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Endocrinologic profile and ongoing pregnancy rates. RESULT(S): Among 43 women treated with corifollitropin alfa, mean E(2) levels showed an increasing pattern during the follicular phase, reaching 825 ng/L on the day of hCG administration, whereas FSH values showed a marked increase during the first 5 days, reaching a mean value of 35 IU/L and remaining above 20 IU/L during the late follicular phase. Cycle cancellation rate was 32.6% and embryo transfer rate 53.3%. Five patients (11.7%) had a positive hCG test and three (7%) had an ongoing pregnancy. Ongoing pregnancy rates were 11.1% per oocyte retrieval and 13% per embryo transfer. Ongoing pregnancy rates per patient did not significantly differ compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). CONCLUSION(S): Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH antagonist protocol results in low pregnancy rates, similarly to conventional stimulation with a short agonist protocol.

Human trophectoderm cells are not yet committed.

STUDY QUESTION: Are human trophectoderm (TE) cells committed or still able to develop into inner cell mass (ICM) cells? SUMMARY ANSWER: Human full blastocyst TE cells still have the capacity to develop into ICM cells expressing the pluripotency marker NANOG, thus they are not yet committed. WHAT IS KNOWN ALREADY: Human Day 5 full blastocyst TE cells express the pluripotency markers POU5F1, SOX2 and SALL4 as well as the TE markers HLA-G and KRT18 but not yet CDX2, therefore their developmental direction may not yet be definite. STUDY DESIGN, SIZE, DURATION: The potency of human blastocyst TE cells was investigated by determining their in vitro capacity to develop into a blastocyst with ICM cells expressing NANOG; TE cells were isolated either by aspiration under visual control or after labeling with fluorescent 594-wheat germ agglutinin. Further on, aspirated TE cells were also labeled with fluorescent PKH67 and repositioned in the center of the original embryo. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human preimplantation embryos were used for research after obtaining informed consent from IVF patients. The experiments were approved by the Local Ethical Committee and the 'Belgian Federal Committee on medical and scientific research on embryos in vitro'. Outer cells were isolated and reaggregated by micromanipulation. Reconstituted embryos were analyzed by immunocytochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: Isolated and reaggregated TE cells from full human blastocysts are able to develop into blastocysts with ICM cells expressing the pluripotency marker NANOG. Moreover, the majority of the isolated TE cells which were repositioned in the center of the embryo do not sort back to their original position but integrate within the ICM and start to express NANOG. LIMITATIONS, REASONS FOR CAUTION: Owing to legal and ethical restrictions, manipulated human embryos cannot be transferred into the uterus to determine their totipotent capacity. The definitive demonstration that embryos reconstructed with TE cells are a source of pluripotent cells is to obtain human embryonic stem cell 'like' line(s), which will allow full characterization of the cells. WIDER IMPLICATIONS OF THE FINDINGS: Our finding has important implications in reproductive medicine and stem cell biology because TE cells have a greater developmental potential than assumed previously. STUDY FUNDING/COMPETING INTEREST(S): Scientific Research Foundation-Flanders (FWO-Vlaanderen) and Research Council (OZR) of the Vrije Universiteit Brussel. None of the authors declared a conflict of interest.

Spontaneous triggering of ovulation versus HCG administration in patients undergoing IUI: a prospective randomized study.

The objective of this prospective randomized study was to assess whether spontaneous triggering of ovulation by detecting LH rise with serial serum testing, results in higher pregnancy rates as compared with administration of human chorionic gonadotrophin (HCG) in patients undergoing intrauterine insemination (IUI) in natural cycles. The trial was registered in clinicaltrials.gov as NCT01414673. Three hundred patients treated by IUI in natural cycles at the Centre of Reproductive Medicine of the Dutch-Speaking Brussels Free University were randomized to either spontaneous triggering of ovulation (spontaneous LH group) (n=150) or administration of HCG (n=150). Donor spermatozoa was used in 197/300 patients (65.67%). The duration of the follicular phase was significantly higher in the spontaneous LH group as compared with the HCG group (P=0.004). However, the ongoing pregnancy rate was significantly higher in the spontaneous LH group as compared with the HCG group (34/150 versus 16/150, P=0.008; difference 12.0%, 95% CI - 3.6 to 20.4). The use of LH for timing ovulation in natural cycles might be the best way to maximize the probability of pregnancy for patients undergoing IUI. It remains unclear whether the probability of pregnancy is associated with the mode of ovulation triggering in intrauterine insemination (IUI) natural cycles. The aim of this study was to assess prospectively whether spontaneous triggering of ovulation by detecting LH rise results in higher pregnancy rates as compared to administration of human chorionic gonadotrophin (HCG) in patients undergoing IUI. Based on our results, spontaneous triggering of ovulation is associated with significantly higher ongoing pregnancy rates compared with administration of HCG in patients undergoing IUI. Therefore, the use of LH for timing ovulation in natural cycles might be the best way to maximize the probability of pregnancy for patients undergoing IUI.

Obstetric outcome in donor oocyte pregnancies: a matched-pair analysis.

BACKGROUND: To investigate the obstetrical and perinatal impact of oocyte donation, a cohort of women who conceived after OD was compared with a matched control group of women who became pregnant through in vitro fertilisation with autologous oocytes (AO). METHODS: A matched-pair analysis has been performed at the Centre for Reproductive Medicine of the UZ Brussel, Dutch speaking Free University of Brussel. A total of 410 pregnancies resulted in birth beyond 20 weeks of gestation occurring over a period of 10 years, including 205 oocyte donation pregnancies and 205 ICSI pregnancies with autologous oocytes (AO). Patients in the OD group were matched on a one-to-one basis with the AO group in terms of age, ethnicity, parity and plurality. Matched groups were compared using paired t-tests for continuous variables and McNemar test for categorical variables. A conditional logistic regression analyses was performed adjusting for paternal age, age of the oocyte donor, number of embryos transferred, and singleton/twin pregnancy. RESULTS: Oocyte donation was associated with an increased risk of pregnancy induced hypertension (PIH) (matched OR: 1.502 CI: 1.024-2.204), and first trimester bleeding (matched OR: 1.493 CI: 1.036-2.15). No differences were observed between the two matched groups with regard to gestational age, mean birth weight and length, head circumference and Apgar scores. CONCLUSIONS: Oocyte donation is associated with an increased risk for PIH and first trimester bleeding independent of the recipients' age, parity and plurality, and independent of the age of the donor or the partner. However, oocyte donation has no impact on the overall perinatal outcome.