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Biomedical subjects

Antonio Pellicer

Publications and source records attributed to Antonio Pellicer.

At least 19 recordsLinked to original sources

Early pregnancy loss in women stimulated with gonadotropin-releasing hormone antagonist protocols according to oral contraceptive pill pretreatment.

OBJECTIVE: To evaluate and compare the risk of early pregnancy loss in patients stimulated with GnRH antagonist protocols according to oral contraceptive pill (OCP) pretreatment. DESIGN: Retrospective case-control study. SETTING: Instituto Valenciano de Infertilidad. University of Valencia. Spain. PATIENT(S): One thousand five hundred thirty-nine patients, aged <36, stimulated with GnRH antagonists for IVF between January 1, 2000 and November 1, 2005. INTERVENTION(S): Reproductive outcome was compared based on the application (or not) of OCP pretreatment: 944 women were included in the OCP group and 595 in the non-OCP group. The Student's t test was used for statistics. MAIN OUTCOME MEASURE(S): Pregnancy, biochemical pregnancy, ectopic pregnancy, early clinical pregnancy loss, early pregnancy loss, and ongoing pregnancy rates. RESULT(S): No significant differences were observed in any of the outcome parameters. Early pregnancy loss rates were similar: 23% in the OCP pretreatment group versus 19.2% in the non-OCP pretreatment group. However, longer periods of ovarian stimulation and higher doses of gonadotropins needed to be employed in the OCP group. CONCLUSION(S): There is not sufficient evidence to confirm OCP pretreatment as a risk factor for miscarriage in patients stimulated with GnRH antagonist protocols.

Adult↗

Heteroparental blastocyst production from microsurgically corrected tripronucleated human embryos.

OBJECTIVE: To prove the efficiency of identification and removal of one of the surplus paternal pronuclei in dispermic IVF zygotes to obtain heteroparental blastocysts. DESIGN: Experimental. SETTING: One hundred fourteen tripronucleated (3PN) embryos from conventional IVF. PATIENT(S): After informed and signed consent, the patients from Instituto Valenciano Infertilidad (IVI), Valencia, donated their abnormally fertilized embryos. INTERVENTION(S): Seventy-two embryos were diploidized by microsurgical removal of the pronucleus located at the farthest position to the second polar body. Forty-two 3PN embryos served as controls. MAIN OUTCOME MEASURE(S): Survival and correction rate; in vitro development up to the blastocyst stage; X, Y, and 18 chromosome determination by triple fluorescent in situ hybridization and, inheritance analysis for 10 polymorphic repeat regions using polymerase chain reaction (PCR) amplification and sequencing. RESULT(S): Seventy-eight percent of 3PN zygotes (56/72) survived manipulation and eventually 51 zygotes had two pronuclei (71%). Forty-one percent of manipulated embryos progressed in vitro to the blastocyst stage (21/51). Fluorescent in situ hybridization analysis performed on eight manipulated embryos confirmed their diploid state; all four controls were triploid. Heteroparental inheritances were also confirmed in four of six manipulated embryos. CONCLUSION(S): Heteroparental blastocysts can be derived from corrected dispermic zygotes.

Adult↗

The effectiveness of modified sperm washes in severely oligoasthenozoospermic men infected with human immunodeficiency and hepatitis C viruses.

Men who are seropositive for human immunodeficiency virus (HIV) or hepatitis C virus now can father children safely, thanks to sperm washing and nested polymerase chain-reaction techniques, followed by intracytoplasmic sperm injection. However, in a small percentage of such patients, it is impossible to recover spermatozoa after said procedures because of their highly impaired spermatogenesis. We have established that less rigorous methods, such as repeated centrifugation, yield nested polymerase chain-reaction HIV- and hepatitis C virus-negative specimens, even in sperm samples from men with severe oligoasthenozoospermia.

Adult↗

Effect of sperm glutathione peroxidases 1 and 4 on embryo asymmetry and blastocyst quality in oocyte donation cycles.

OBJECTIVE: To prospectively determine the impact of concrete components of the sperm oxidative glutathione stress system in terms of enzymatic activity and mitochondrial RNA (mRNA) expression on embryo quality and reproductive outcome. Human spermatozoa use the glutathione system to inactivate reactive oxygen metabolites, and there is a close correlation between some components of the glutathione system and male fertility. However, very few data are published regarding this system in sperm cells and its effect on fertilization ability and embryo development in human beings. DESIGN: An oocyte-donation model, used to homogenize the female factor. SETTING: University-affiliated private IVF setting. PATIENT(S): Semen samples from infertile males (n = 43) of couples undergoing oocyte-donation cycles (n = 43). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gene expression and activity of glutathione peroxidases (GPXs) 1 and 4, glutathione reductase, and intracellular glutathione (GSH) by fluorescent quantitative polymerase chain reaction and spectrophotometry, respectively. RESULT(S): Fertilization rate, pronuclear number, asymmetry, and pronuclear body distribution were not correlated with any sperm glutathione parameters that were considered. When day 3 embryo parameters were evaluated, only GPX4 mRNA expression in sperm cells was statistically significantly lower when asymmetric embryos were observed. Also, worst embryo development and morphology on day 5 was statistically significantly correlated with lower sperm GPX1 activity (101.07 vs. 258.8 IU/mg protein). Glutathione system analysis in fresh sperm was not statistically significantly different in patients achieving pregnancy compared with those who not, and we did not find any correlation with implantation rate. CONCLUSION(S): We have been able to correlate embryo morphology on day 3 with the sperm expression of GPX family members. The results indicate that sperm-derived mRNA may condition human embryo quality and persist even to blastocyst stage. The correlation of the sperm GPX family mRNA expression with embryo health appears quite promising for discovery of molecular causes of male infertility.

Adult↗

Low-dose dopamine agonist administration blocks vascular endothelial growth factor (VEGF)-mediated vascular hyperpermeability without altering VEGF receptor 2-dependent luteal angiogenesis in a rat ovarian hyperstimulation model.

No specific treatment is available for ovarian hyperstimulation syndrome (OHSS), the most important complication in infertile women treated with gonadotropins. OHSS is caused by increased vascular permeability (VP) through ovarian hypersecretion of vascular endothelial growth factor (VEGF)-activating VEGF receptor 2 (VEGFR-2). We previously demonstrated in an OHSS rodent model that increased VP was prevented by inactivating VEGFR-2 with a receptor antagonist (SU5416). However, due to its toxicity (thromboembolism) and disruption of VEGFR-2-dependent angiogenic processes critical for pregnancy, this kind of compound cannot be used clinically to prevent OHSS. Dopamine receptor 2 (Dp-r2) agonists, used in the treatment of human hyperprolactinemia including pregnancy, inhibit VEGFR-2-dependent VP and angiogenesis when administered at high doses in animal cancer models. To test whether VEGFR-2-dependent VP and angiogenesis could be segregated in a dose-dependent fashion with the Dp-r2 agonist cabergoline, a well-established OHSS rat model supplemented with prolactin was used. A 100 microg/kg low-dose Dp-r2 agonist cabergoline reversed VEGFR-2-dependent VP without affecting luteal angiogenesis through partial inhibition of ovarian VEGFR-2 phosphorylation levels. No luteolytic effects (serum progesterone levels and luteal apoptosis unaffected) were observed. Cabergoline administration also did not affect VEGF/VEGFR-2 ovarian mRNA levels. Results in the animal model and the safe clinical profile of Dp-r2 agonists encouraged us to administer cabergoline to oocyte donors at high risk for developing the syndrome. Prophylactic administration of cabergoline (5-10 microg/kg x d) decreased the occurrence of OHSS from 65% (controls) to 25% (treatment). Therefore, a specific, safe treatment for OHSS is now available.

Animals↗

Ultrastructure of preimplantation genetic diagnosis-derived human blastocysts grown in a coculture system after vitrification.

OBJECTIVE: To evaluate ultrastructural features of preimplantation genetic diagnosis (PGD) blastocysts before and after vitrification. DESIGN: Descriptive study of both vitrified and fresh hatching blastocysts. SETTING: PGD program at the Instituto Universitario, Instituto Valenciano de Infertilidad. PATIENT(S): Patients undergoing PGD donated their abnormal embryos for research (n = 26). INTERVENTION(S): Biopsied embryos were cultured in the presence of human endometrial cells until day 6. Sixteen blastocysts were vitrified. A total of 11 high-scored hatching blastocysts, 6 warmed and 5 fresh, were fixed for ultrastructure. MAIN OUTCOME MEASURE(S): The cytoskeleton structure, type of intercellular junctions, and basic intracellular organelles in trophoectoderm cells and the inner cell mass were analyzed. RESULT(S): Ten of 16 blastocysts (62%) survived the warming process. Six of these showed no signs of cell degeneration and light microscopy revealed similar ultrastructural characteristics to those of controls. However, in trophoectoderm cells from both fresh and cryopreserved blastocysts, a reduced number of tight junctions and the presence of degradation bodies were detected. CONCLUSION(S): The particular ultrastructural features observed in PGD-derived blastocysts could be related to embryo manipulation and culture conditions. Vitrification does not seem to alter blastocysts, as those that survive hatching do not display detectable cellular alterations when observed through electron microscopy.

Blastocyst↗

Plasma levels of soluble vascular endothelial growth factor receptor-1 may determine the onset of early and late ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a life-threatening condition associated with ovarian stimulation. Its pathophysiology is unknown and its treatment continues to be empirical. Early (E)- and late (L)-OHSS occur in women at risk, though not in all cases. Vascular endothelial growth factor (VEGF) is related to increased vascular permeability in OHSS. We analysed the dynamics of the VEGF system in E- and L-OHSS. METHODS: A prospective cohort of women undergoing IVF-ICSI treatment were divided into groups. E-OHSS: Nonpregnant patients classified as women not at risk (group 1) (n = 11) and patients at risk who did not (group 2) (n = 18) and did (group 3) (n = 8) develop severe OHSS. Blood was drawn on the day of ovum retrieval (day 0) and 3, 6, 10 and 14 days later. L-OHSS: Single pregnancies classified as women who did not (group 4) (n = 8) and did develop (group 5) (n = 4) OHSS. Single pregnancies after oocyte donation (OD) (n = 4) were compared with groups 4 and 5 (IVF-ICSI). Blood was obtained weekly (weeks 4-12). Total VEGF (VEFG-A), free (f)-VEGF and soluble VEGF receptor 1 (sVEGFR-1) in plasma and in serum alpha2-macroglobulin (M) were also measured. RESULTS: Group 3 showed significantly (P < 0.05) higher VEFG-A and f-VEGF than group 1 on day 6 because of lower sVEGFR-1 secretion. Similarly, group 5 had significantly (P < 0.05) more VEFG-A and f-VEGF and less sVEGFR-1 than group 4. Oocyte donation was associated with decreased sVEGFR-1 secretion, and alpha2M was not relevant in OHSS development. CONCLUSION: In E- and L-OHSS, the ability to secrete sVEGFR-1 and bind VEGF seems to be the determinant factor in OHSS. f-VEGF acts locally in the ovary.

Adult↗

Potential pitfalls in fetal neurosonography.

OBJECTIVE: To present anatomic variants of the fetal brain and artifacts related to scanning techniques that could be misinterpreted as abnormalities on prenatal neurosonographic studies. METHODS: The findings were derived from fetal neurosonographic studies performed routinely from 16 to 36 weeks' gestation during the last 3 years, supervised by a sonologist specialized in neonatal cranial sonography. RESULTS: The pitfalls were divided into three groups: brain parenchyma, ventricular system and choroid plexus. We provide images of these pseudolesions and clues to their differentiation from true brain pathology. CONCLUSIONS: Knowledge of misleading images seen on fetal neurosonographic studies that could be misinterpreted as lesions is essential for the proper interpretation of these studies and will help avoid the use of more invasive diagnostic tests. To the best of our knowledge, the majority of the pitfalls presented here have only been described in neonates.

Artifacts↗

Value of the sperm deoxyribonucleic acid fragmentation level, as measured by the sperm chromatin dispersion test, in the outcome of in vitro fertilization and intracytoplasmic sperm injection.

OBJECTIVE: To determine the prognostic value of sperm DNA fragmentation levels, as measured by the sperm chromatin dispersion (SCD) test, in predicting IVF and ICSI outcome. DESIGN: Double-blind prospective study. SETTING: University-affiliated private IVF setting. PATIENT(S): A total of 85 couples undergoing infertility treatment with IVF/ICSI. INTERVENTION(S): Analysis of DNA fragmentation by the SCD test in 170 aliquots obtained from the ejaculate and from the processed semen used for assisted reproductive technologies (ART). MAIN OUTCOME MEASURE(S): Percentage of spermatozoa with fragmented DNA was statistically correlated with embryo quality and reproductive success. RESULT(S): Fertilization rate was inversely correlated with DNA fragmentation (r = -0.245 P = .045). Higher DNA fragmentation rate gave an increased proportion of zygotes showing asynchrony between the nucleolar precursor bodies of zygote pronuclei (73.8% vs. 28.8% P < .001). In addition, the slower embryo development and worst morphology on day 6 was correlated with higher sperm DNA fragmentation (47.7% vs. 29.4% P = .044). We also observed a negative correlation between DNA fragmentation and the implantation rate (r = -0.250 P = .042). However, SCD test values were not statistically different in cycles that resulted in a pregnancy compared with those that did not (33.2 vs. 28.2 and 32.4 vs. 34.7). CONCLUSION(S): This is the first report that describes a correlation between sperm DNA integrity, as measured by the SCD test, and fertilization rate, embryo quality, and implantation rate in IVF/ICSI. The degree of DNA fragmentation was inversely correlated with fertilization rate, synchrony of the nucleolar precursor bodies' pattern in pronuclei, embryo ability to achieve blastocyst stage, and embryo morphological quality. Because SCD test values were correlated with embryo quality and blastocyst rate, the lack of correlation between sperm DNA fragmentation and pregnancy outcome in IVF might be due to embryo selection before transfer. The ability of the SCD test to predict the blastocyst rate after IVF/ICSI warrants further study.

Adult↗

Coasting for the prevention of ovarian hyperstimulation syndrome: much ado about nothing?

OBJECTIVE: To review and critique the literature and our own experience regarding coasting as a strategy to prevent ovarian hyperstimulation syndrome (OHSS). DESIGN: Identification of relevant clinical literature through PubMed and EMBASE databases, as well as the experience of our institution with this approach. CONCLUSION(S): Coasting is a rescue procedure that can be avoided by carefully adjusting the gonadotropin dosage. It is a good alternative that can be used to avoid cycle cancellation in extremely high responders to controlled ovarian hyperstimulation, who have a high risk of developing severe OHSS. Even if OHSS develops after coasting, both its incidence and severity will be diminished. Each case should be individually counseled to determine whether the patient should be coasted, and her hypothetical risks and benefits should be evaluated. Until the multifactorial etiopathogenesis of OHSS is completely understood, absolute prevention will not be possible, but coasting is definitely of great benefit.

Dose-Response Relationship, Drug↗

Sperm cryopreservation in oncological patients: a 14-year follow-up study.

OBJECTIVE: Oncologic treatments can destroy spermatogenic dividing cells and cause azoospermia which could be irreversible. Sperm banking is the best option to preserve male fertility after these treatments. It is easy, inexpensive, and safe. To date, few clinical data are available about large series of cancer patients. Our objective was to determine the usefulness of these preventive sperm freezing protocols. DESIGN: Prospective study. SETTING: University-affiliated private fertility center. PATIENT(S): One hundred eighty-six cancer patients who banked sperm samples at our center before surgery or chemo- or radiotherapy treatments from 1991 to 2004. INTERVENTION(S): Conjugal status, age, type of cancer, treatment, and future use (if any) of the cryopreserved sperm samples for assisted reproduction technology (ART), and cycle results were recorded, analyzed, and compared with a control group. MAIN OUTCOME MEASURE(S): Basic sperm analysis of semen samples from cancer patients prior to freezing, after thawing, and after capacitation for ART. RESULT(S): A total of 320 semen samples were frozen before antineoplasic treatment. Six months later, 27% of the males recovered normal sperm production. From all frozen samples, 8.7% were discarded; the reasons were pregnancy achievement (55%), normal sperm production (28%), and patient death (18%). Finally, 5 IUI cycles and 30 ICSI cycles were done from frozen samples, with 1 and 15 pregnancies, respectively; results were comparable with those obtained in a control group. CONCLUSION(S): A significant number of males who cryopreserved semen samples before receiving antitumoral treatments have employed them. The results obtained showed that this is the strategy of choice, aiming to preserve fertility for the future, because the cost/benefit ratio is favorable. Patients should be counseled accordingly.

Adult↗

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

OBJECTIVE: To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. DESIGN: A MEDLINE computer search was performed to identify relevant articles. RESULT(S): Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. CONCLUSION(S): Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.

Adiponectin↗

Delaying the initiation of progesterone supplementation until the day of fertilization does not compromise cycle outcome in patients receiving donated oocytes: a randomized study.

OBJECTIVE: To determine whether the initiation of P supplementation as artificial luteal phase support (day -1, day 0, or day +1 of egg donation) in extensive programs of ovum donation influences cycle cancellation, pregnancy outcome, and implantation rate in day 3 embryo transfers. DESIGN: Prospective randomized trial. SETTING: Oocyte donation program at the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): Three hundred recipients with normal ovarian function, absence of uterine anomalies, and undergoing their first egg donation were recruited between September 2003 and September 2004. INTERVENTION(S): A computer-based randomization divided the recipients into three groups when hCG was administered to their matched donors. The first group (group A) started P supplementation the day before oocyte retrieval; the second group (group B) started P supplementation on the day of the oocyte retrieval; and the third group (group C) started P supplementation 1 day after the egg retrieval once fertilization was confirmed. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and ongoing pregnancy rates were the primary outcome measures considered. The secondary outcome measure was the cancellation rate, especially due to fertilization failure. RESULT(S): Global cancellation rate and cancellation rate due to fertilization failure were significantly higher in group A (12.4% and 8.2%, respectively) than in group C (3.3% and 0%, respectively). Reproductive outcome was similar in all the groups except for a higher biochemical pregnancy rate in group A (12.9%) than in groups B (6.6%) and C (2.3%). CONCLUSION(S): Initiation of P on day +1 of embryo development decreases cancellation rates of day 3 embryo transfers in extensive programs of ovum donation without any deleterious effect on pregnancy outcome or implantation rate.

Adolescent↗

Derivation and characterization of three new Spanish human embryonic stem cell lines (VAL -3 -4 -5) on human feeder and in serum-free conditions.

A total of 184 human embryos, frozen for >5 years, were donated; informed consent was obtained according to Spanish law 45/2003. Survival rate was 40% and three out of 24 blastocysts (12.5%) developed into putative hESC lines, named VAL-3, VAL-4, and VAL-5. The derivation process was performed on microbiologically tested and irradiated human foreskin fibroblasts and designed to minimize contact with xeno-components in knockout DMEM supplemented with knockout serum replacement, and basic fibroblast growth factor. Fingerprinting and HLA typing of the cell lines allowed their identification and traceability. Karyotype was normal for VAL-3 (46XY), VAL-4 (46XX) and VAL-5 (46XX). All three hESC lines expressed specific markers for non-differentiation (Nanog, stage-specific embryonic antigen-4 [SSEA-4], tumour-related antigen [TRA]-1-60, and TRA-1-81) and were negative for SSEA-1. RT-PCR further demonstrated the expression of Oct-4, Sox2, Rex-1, Nanog, Cripto, Thy-1, and Lefty-A. Furthermore, they were found to be negative for classical differentiation markers such as neurofilament heavy chain (ectoderm), renin (mesoderm), and amylase (endoderm). All three cell lines displayed high levels of telomerase activity, and were shown to successfully overcome cryopreservation and thawing. Finally, these three new hESC lines have demonstrated the potential to differentiate in vitro and in vivo (teratoma formation) into cell types originating from all three germ layers.

Animals↗

Obesity and assisted reproductive technology outcomes.

Obesity is a rising health problem in Western societies. It has been related to increased morbidity and mortality rates due to several pathologies. In the field of gynaecology and reproduction, obesity is associated with menstrual disorders, hirsutism, infertility, miscarriage and obstetric complications. It is known to impair human reproduction through different mechanisms such as insulin resistance, hyperandrogenism and elevated leptin levels. Weight management and dietary intervention can reverse this situation and improve reproductive function. Obesity can also impair the outcome of assisted reproductive technologies. The lower probability of a healthy live birth described in obese women seems to be the result of a combination of lower implantation and pregnancy rates, higher preclinical and clinical miscarriage rates and increased complications during pregnancy for both mother and fetus. Studies performed in infertile women undergoing assisted reproduction technologies indicate that the ovary plays a leading, but not exclusive, role in the fertility prognosis of these patients. The endocrine and metabolic environment may affect oocyte quality and, therefore, embryo development, implantation and pregnancy outcome. The endometrium seems to play a subtle role in the more negative reproductive outcome of obese women, according to recent studies based on the ovum donation model.

Endometrium↗

The role of the leptin in reproduction.

PURPOSE OF REVIEW: Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function. RECENT FINDINGS: This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo-pituitary-gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reproductive tissues, indicating that this system could be also implicated in several processes such as embryo development, implantation and pregnancy. Moreover, disorders of the leptin system have been related to some reproductive pathologies such as pre-eclampsia and polycystic ovary syndrome. However, controversy surrounds several aspects of the action of leptin in reproduction that require a deeper investigation of this system. SUMMARY: Results to date suggest that this system could be implicated in important reproductive processes such as embryonic development and implantation. Moreover, understanding the role of leptin might be useful for new treatments in reproductive pathologies.

Embryo Implantation↗

Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study.

BACKGROUND: Sperm DNA integrity has been used as a new marker of sperm quality in the prediction of pregnancy. Nevertheless, no previous study has been performed by analysing the same samples that were employed in assisted reproduction. The main objective of this work was to correlate sperm chromatin dispersion (SCD), measured by the SCD test, with semen parameters and pregnancy outcome in intrauterine insemination (IUI). METHODS: A total of 100 semen samples obtained from males of couples undergoing IUI were analysed by the SCD test before and after swim-up, and the results were correlated with semen parameters and pregnancy outcome. RESULTS: SCD was negatively correlated with sperm motility in both ejaculated and processed semen. Sperm recovered by swim-up did not show a significant improvement in DNA integrity. No correlation was found between SCD and pregnancy outcome in IUI. CONCLUSIONS: DNA dispersion, as measured by the SCD test, is not correlated with pregnancy outcome in IUI.

Chromatin↗

First trimester biochemical screening for Down's syndrome in singleton pregnancies conceived by assisted reproduction.

BACKGROUND: Serum biochemical markers [free betahCG (fbetahCG); pregnancy-associated plasma protein-A (PAPP-A)] used in first trimester Down's syndrome screening have not been fully investigated in pregnancies achieved by assisted reproduction techniques. We present data on pregnancies conceived by all types of assisted reproduction techniques, including pregnancies following ovum donation (OD) and a large sample by ICSI. METHODS: First trimester Down's syndrome screening was performed in 1054 normal singleton pregnancies: natural conception (n = 498), ovulation induction (OS, n = 97), IVF (n = 47), ICSI (n = 222) and OD (n = 190). RESULTS: No differences in maternal levels of fbetahCG and PAPP-A, measured by the Kryptor system, appeared between naturally conceived pregnancies (n = 498) and those obtained with assisted reproduction techniques (n = 556). Several differences were apparent when comparing fbetahCG levels between different technologies but PAPP-A levels only differed between OS and IVF pregnancies (P < 0.05). In a further small study, no differences were observed using frozen embryos (n = 37), preimplantation genetic diagnosis (n = 53) or sperm from testicular biopsy (n = 21). CONCLUSIONS: Data accumulated so far suggest that first trimester biochemical markers either do not need any adjustments (e.g. in pregnancies obtained after OS and ICSI), or have very little impact (e.g. IVF pregnancies) or no impact (e.g. OD pregnancies) on the false positive rates.

Biomarkers↗