Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome

BACKGROUND: The aim of this study was to compare the maternal mid-trimester free beta-HCG and alpha-fetoprotein (AFP) levels in pregnancies conceived by assisted reproduction technology and spontaneous pregnancies in Down's syndrome screening. The influence of the number of embryos transferred and the amount of gonadotrophins used on the marker levels was also evaluated. METHODS: The study population consisted of 58 IVF, 32 ICSI and 26 frozen embryo transfer (FET) singleton pregnancies. The levels of beta-HCG and AFP were compared with the control group of 6548 singleton spontaneous pregnancies. RESULTS: The false positive rate (FPR) in the Down's syndrome screening was 19% overall in assisted reproductive technology pregnancies, being highest (30.8%) in the FET group. The free beta-HCG multiples of the median (MoM) values were statistically significantly elevated only in the FET group (1.33 MoM; P = 0.012). A positive correlation between the number of embryos transferred and the marker levels was observed in the IVF group. No correlation was found between the amount of gonadotrophin medication used and the marker levels. CONCLUSIONS: The present data confirm that the overall FPR in the serum screening for Down's syndrome in assisted reproduction pregnancies is high, resulting in unnecessary invasive procedures.     

Maternal serum alpha-fetoprotein and human chorionic gonadotrophin in pregnancies conceived after intracytoplasmic sperm injection and conventional in-vitro fertilization.

Data in the Caucasian population suggest that maternal serum alpha-fetoprotein (AFP) and unconjugated oestriol concentrations are reduced and human chorionic gonadotrophin (HCG) concentrations are elevated in pregnancies conceived after in-vitro fertilization (IVF), leading to a higher than expected Down's syndrome screen-positive rate. There are no previous reports on the serum marker values in pregnancies conceived after intracytoplasmic injection (ICSI). Between 1996 and 1998, we measured maternal serum total HCG and AFP concentrations between 15 and 20 weeks gestation in 42 in-vitro fertilization (IVF) pregnancies and 23 ICSI pregnancies with known normal outcome. The results were compared with that of 2799 naturally occurring singleton pregnancies who were known to have a normal outcome. Median AFP multiple of the median (MOM) in ICSI pregnancies was significantly reduced to 0.76 compared with both that of the controls and that of the IVF pregnancies. For the IVF pregnancies, median HCG MOM was elevated to 1.15, and median AFP MOM was reduced to 0.88 compared with the controls, but these differences were not statistically significant. In both the IVF and ICSI pregnancies the changes might result in a falsely high Down's syndrome risk. In particular, the reduced AFP concentration in ICSI pregnancies was substantial. If this preliminary finding is substantiated by other series, the appropriate adjustment needs to be made to allow for valid interpretation of the screen result and to avoid an unnecessarily high false positive rate.     

Maternal serum hCG and alpha-fetoprotein levels in pregnancies conceived after IVF or ICSI with fresh and frozen-thawed embryos

BACKGROUND: Studies have shown that levels of serum markers of Down's syndrome were altered in pregnancies conceived after IVF, though the reason for this remains unknown. METHODS: Second-trimester maternal serum levels of hCG and alpha-fetoprotein (AFP) in pregnancies conceived with fresh and frozen-thawed embryos after assisted reproduction were compared with those conceived spontaneously. RESULTS: There were 203 pregnancies with fresh embryo transfers (130 IVF cases, 73 ICSI cases) and 98 pregnancies with frozen-thawed embryo transfers (61 IVF cases, 37 ICSI cases). The controls consisted of 17 145 spontaneous pregnancies. The median hCG multiples of the median (MoM) was significantly increased to 1.24 in 98 pregnancies conceived after frozen embryo transfer. This elevation was observed only in the IVF-frozen embryo transfer subgroup (P < 0.001), but not in the ICSI-frozen embryo transfer subgroup. The median AFP MoM for 203 pregnancies after fresh embryo transfer was 0.90. Among the subgroups, the median AFP MoM was significantly reduced to 0.90 and 0.86 in IVF-embryo transfer (P = 0.04) and ICSI-embryo transfer (P = 0.001) pregnancies respectively, and significantly raised to 1.20 in the IVF-frozen embryo transfer subgroup. CONCLUSIONS: The degree of alterations in maternal serum hCG and AFP levels varied between fresh and frozen-thawed embryos, and also between the mode of fertilization. Pregnancies resulting from ICSI or frozen embryo transfer should be regarded as distinct entities from those of IVF-embryo transfer.     

First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction.

BACKGROUND: The possible effect of assisted reproduction on first-trimester screening for trisomy 21 was examined by fetal nuchal translucency thickness (NT), maternal serum free beta-human chorionic gonadotrophin (HCG) and pregnancy-associated plasma protein-A (PAPP-A). METHODS: Parameters were measured at 11-14 weeks in 411 singleton pregnancies achieved by controlled ovarian stimulation, including 220 that had undergone IVF. Results were compared with 1233 singleton pregnancies conceived spontaneously. RESULTS: In the IVF pregnancies, the median fetal NT was not significantly different from that in controls, whilst the median free beta-HCG was significantly increased, and PAPP-A was significantly decreased. In the intracytoplasmic sperm injection group, fetal NT and free beta-HCG values were not significantly different from those in controls, but PAPP-A was significantly decreased. In those pregnancies achieved by ovarian stimulation, neither fetal NT, free beta-HCG nor PAPP-A were significantly different from the control group. CONCLUSIONS: In IVF pregnancies, screening for trisomy 21 by fetal NT, maternal serum free beta-HCG and PAPP-A levels may be associated with a 1.2% higher false-positive rate than in natural conception.     

Does ICSI affect early serum beta-HCG in pregnancies achieved after IVF?

This study was conducted to compare early serum human chorionic gonadotrophin (HCG) concentrations in singleton pregnancies achieved after intracytoplasmic sperm injection (ICSI), with those achieved after conventional in-vitro fertilization (IVF). Early serum HCG, 14-16 days after embryo transfer, was analysed in 99 IVF pregnancies achieved after ICSI (group A), and compared to 105 conventional IVF pregnancies (group B). All women were treated at the IVF Unit, Lis Maternity Hospital. Records were studied retrospectively. The mean +/- SE serum HCG concentration on day 14 after embryo transfer in group A was 190.5 +/- 17.4 mIU/ml, compared to 195.7 +/- 14.03 mIU/ml in group B. HCG concentration 14 days after embryo transfer in both groups A and B was higher in women with mechanical factor than in couples with male factor infertility or unexplained infertility (246 +/- 31.4, 183.3 +/- 16.4, 177.98 +/- 14.3 mIU/ml respectively). On the 16th day after embryo transfer, the HCG concentration increased, and the difference between the groups was maintained. Only in the subgroup of unexplained infertility did we find a difference in concentrations of HCG between ICSI and conventional IVF: on the 16th day following embryo transfer in this group there was a significant difference in HCG concentrations (395. 8 +/- 21 and 545.6 +/- 45.7 respectively; P = 0.04). HCG concentrations did not differ overall in the conventional IVF pregnancies compared with those achieved by ICSI. However, a statistical difference in early serum HCG concentrations was found in relation to the aetiology of infertility.     

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.     

The contribution of maternal serum markers in the early prenatal diagnosis of molar pregnancies

The aim of this study was to evaluate the usefulness of maternal serum markers in the early prenatal diagnosis of molar pregnancies. The ultrasound features, cytogenetic and histopathological findings of 10 cases of molar pregnancy diagnosed at 11-13 weeks of gestation were compared retrospectively with the maternal serum concentrations of human chorionic gonadotrophin (HCG), alpha fetoprotein (AFP), pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta1-glycoprotein (SP1). Free beta-HCG and intact HCG concentrations were very high [> or = 2.5 multiples of the median (MoM)] in all cases. AFP concentrations were extremely low in all cases of singleton complete moles (< or = 0.5 MoM) and were high in one case of twin complete mole, in one case of triploid partial mole and two cases of euploid partial mole (> or = 2.5 MoM). Serum PAPP-A and SP1 were high in complete moles. The combined use of ultrasound features, maternal serum proteins and fetal cytogenetic findings should enable the early differential diagnosis in utero and perinatal management of those molar pregnancies presenting with an anatomically normal fetus.     

Basal and stimulation day 5 anti-Mullerian hormone serum concentrations as predictors of ovarian response and pregnancy in assisted reproductive technology cycles stimulated with gonadotropin-releasing hormone agonist--gonadotropin treatment

BACKGROUND: Anti-Müllerian hormone (AMH) has been recently proposed as a marker for ovarian ageing and poor ovarian response to controlled ovarian hyperstimulation in assisted reproduction cycles. The present study was undertaken to investigate the usefulness of baseline cycle day 3 AMH levels and AMH serum concentrations obtained on the fifth day of gonadotropin therapy in predicting ovarian response and pregnancy in women undergoing ovarian stimulation with FSH under pituitary desensitization for assisted reproduction. METHODS: A total of 80 women undergoing their first cycle of IVF/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproduction programme matching by race, age, body mass index, basal FSH and indication for IVF/ICSI to those in the cancelled group. For each cancelled patient, three IVF/ICSI women who met the matching criteria were included. RESULTS: Basal and day 5 AMH serum concentrations were significantly lower in the cancelled than in the control group. Receiver-operating characteristic (ROC) analysis showed that the capacity of day 5 AMH in predicting the likelihood of cancellation in an assisted reproduction treatment programme was significantly higher than that for basal AMH measurement. However, the predictive capacity of day 5 AMH was not better than that provided by day 5 estradiol. In addition, neither basal nor day 5 AMH or estradiol measurements were useful in the prediction of pregnancy after assisted reproductive treatment. CONCLUSIONS: AMH concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproduction are better predictors of ovarian response than basal AMH measurements. However, AMH is not useful in the prediction of pregnancy. Definite clinical applicability of AMH determination as a marker of IVF outcome remains to be established.     

Serial first- and second-trimester Down's syndrome screening tests among IVF-versus naturally-conceived singletons

BACKGROUND: It has been reported that second-trimester serum markers may be affected by assisted reproduction, leading to a higher false-positive rate. METHODS: A total of 285 naturally and 71 IVF-conceived singletons which underwent a serial disclosure Down's syndrome screening programme were compared. The study protocol included first-trimester combined [nuchal translucency (NT), free beta-HCG and pregnancy-associated plasma protein-A (PAPP-A)] testing. The second-trimester triple serum screening included alpha-fetoprotein (AFP), intact HCG and unconjugated estriol (uE3). After excluding aneuploidies, miscarriages, anatomical anomalies and cases with incomplete follow-up, the serum samples of normal cases were assessed and correlated. RESULTS: NT measurement was not significantly changed in either group. However, the IVF group had lower PAPP-A [0.96 versus 1.05 multiples of normal median (MoM)] and higher AFP (1.13 versus 1.07 median MoM). Both groups had similar rates of first-trimester false-positive results (FPR; 7 and 9% respectively), but the IVF group had a significantly higher mid-gestation FPR rate (10 versus 5%; Pearson chi2, P = 0.029). This has contributed to amniocentesis uptake rates of 15 and 13% for the IVF and natural conception pregnancies respectively. CONCLUSIONS: The IVF group tended to have a significantly higher second-trimester FPR rate. To counterbalance this phenomenon, integrated first- and second-trimester screening tests or the use of NT alone might be a reasonable option that deserves further investigation.     

Cell-free fetal DNA levels in pregnancies conceived by IVF

BACKGROUND: Increased second-trimester levels of maternal serum HCG in IVF conceptions lead to an increased false-positive rate in Down syndrome screening. Increased levels of cell-free fetal DNA (cffDNA) in maternal plasma have been correlated with increased HCG levels. Our aim was to determine whether cffDNA levels are elevated in IVF pregnancies compared with natural pregnancies. METHODS: Sixteen archived second-trimester serum samples from IVF pregnancies were matched with five control samples from naturally conceived pregnancies per case, all carrying a singleton male fetus. cffDNA concentrations were measured by real-time PCR amplification of a Y chromosome sequence and compared with four standard second trimester serum screening markers (alpha-fetoprotein, estriol, HCG and inhibin A). RESULTS: Mean cffDNA levels for cases and controls were 57.9 and 57.1 genome equivalents/ml, respectively (P = 0.95). Mean observed rank (from 1 to 6) of cffDNA was 3.625 in the IVF conceived group, compared with an expected value of 3.5 (P = 0.53). No significant correlations were observed between cffDNA and serum markers. CONCLUSIONS: IVF does not affect levels of cffDNA, which appears to be independent of traditional screening markers (e.g. HCG). Therefore, cffDNA can be used as an additional serum marker (e.g. Down syndrome screening) without adjustment for IVF pregnancies.     

Serum HCG 12 days after embryo transfer in predicting pregnancy outcome

BACKGROUND: Assisted reproduction treatment (ART) entails a risk of ectopic pregnancy and early pregnancy loss. Serum HCG has been found to be predictive of pregnancy outcome. Our aim was to assess the clinical value of a single early HCG assay in ART pregnancies taking into account the aetiology and treatment of infertility. METHODS: During 1994-1999, we studied 774 embryo transfer cycles resulting in pregnancy defined as a serum HCG concentration of > or =5 IU/l on day 12 following embryo transfer. The treatment included IVF in 518, ICSI in 119, and frozen embryo transfer in 137 cycles. Serum HCG concentrations were measured by fluoroimmunometric assay. Pregnancies were classified as viable (live fetus at > or =22 weeks gestation) or non-viable (biochemical pregnancy, miscarriage, ectopic pregnancy and molar pregnancy). Data on the outcomes were retrospectively retrieved from the records. RESULTS: The median HCG concentration was 126 IU/l in viable pregnancies and 31 IU/l in non-viable pregnancies (P < 0.0001). The median HCG concentration was 115 IU/l in singleton pregnancies and 201 IU/l in multiple pregnancies (P < 0.0001). Male factor infertility was associated with viable pregnancies (P = 0.004) and tubal factor with non-viable pregnancies (P = 0.003); the lowest HCG level (88 IU/l) was observed in subjects with both male factor infertility and ICSI treatment (P = 0.001). An HCG value of 76 IU/l emerged as the most suitable cut-off point to predict viable pregnancy. Probabilities of each type of outcome related to the HCG level are given. CONCLUSIONS: A single HCG reading on day 12 after embryo transfer helps to plan the subsequent follow-up. Male factor infertility and ICSI are associated with relatively low HCG values in viable pregnancies.     

Maternal serum inhibin A concentrations in early pregnancy after IVF and embryo transfer reflect the corpus luteum contribution and pregnancy outcome

To compare maternal serum inhibin A concentrations in early pregnancy with pregnancy outcomes and treatment protocols, serum samples were collected from 237 women undergoing in-vitro fertilization (IVF) and embryo transfer cycles. Samples were collected on day 16 after oocyte retrieval for beta human chorionic gonadotrophin (HCG) pregnancy testing and inhibin A measurement. The samples were divided into non-pregnant (n = 128) and pregnant (n = 109) groups, the pregnancies were followed and outcomes determined. Inhibin A concentrations were significantly lower in non-pregnant women than in women with ongoing pregnancies (P: < 0.001) and those resulting in spontaneous abortions (P: < 0.001). In ongoing pregnancies, inhibin A concentrations were significantly lower in the absence of functioning ovaries (donor oocyte/embryo) (P: < 0.01) and in natural cycles (frozen-thawed embryo transfer) (P: < 0.01) compared with concentrations after ovarian stimulation. Further, since inhibin A concentrations were not significantly different between singleton and multiple pregnancies in the ovarian stimulation protocol, the size of the early trophoblast does not appear to influence the secretion of inhibin A. These data strongly support the concept that the corpus luteum is a major source of circulating inhibin A in early pregnancy. Additionally, low concentrations of serum inhibin A may be useful in predicting betaHCG-positive preclinical 'biochemical' pregnancies.     

Comparison of triple serum screening and pregnancy outcome in oocyte donation versus IVF pregnancies

The current study compared triple serum screening results and outcomes in 37 oocyte donation (OD) and 46 self oocyte IVF-conceived singletons of similarly aged women (28.8 +/- 4.4 years and 30.7 +/- 4.5 years respectively). Both groups were followed from their embryo transfer and throughout pregnancy. Although the daily pattern of first-trimester serum beta-human chorionic gonadotrophin (HCG) was similar in both groups, higher mid-gestation HCG serum concentrations were found, i.e. 1.38 and 1.32 multiples of the median (median MoM) for IVF and OD respectively, in comparison with 0.99 median MoM from the same reference laboratory. Only the OD group had significantly increased alpha fetoprotein (AFP) concentrations (1.45 median MoM) (P = 0.002) compared with the reference laboratory. A total of 11% of the IVF and 13% of the OD women were found to be screen positive. In neither group were chromosomal abnormalities detected and no fetal or neonatal deaths were recorded. Seven (15%) of the OD and seven (19%) of the IVF women had an adverse obstetric outcome. Of those cases, six IVF and four OD women had serum HCG > or = 1.2 MoM and five OD women had AFP >1.2 MoM. Therefore, in those pregnancies the high serum HCG concentrations may alert for adverse obstetric outcome rather than indicating a high risk for Down's syndrome fetuses.     

LH serum levels during ovarian stimulation as predictors of ovarian response and assisted reproduction outcome in down-regulated women stimulated with recombinant FSH

BACKGROUND: There has been much debate about the effect of 'residual' LH levels in normogonadotrophic women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH ovarian stimulation. The aim of this prospective study, where receiver-operating characteristic (ROC) analysis was used, was to assess further the usefulness of serum LH levels as predictors of ovarian response, assisted reproduction treatment outcome, and the outcome of pregnancy when measured throughout the ovarian stimulation period in a large cohort of such assisted reproduction treatment women. METHODS: A total of 246 consecutive women undergoing their first cycle of IVF or ICSI treatment were included in this study. Blood samples for hormone analyses were obtained on day S0 (the day when pituitary suppression was evidenced) and every other day from stimulation day 5 (S5) until the day of hCG injection. RESULTS: LH serum levels throughout ovarian stimulation treatment were similar for cancelled (n =32) versus non-cancelled (n = 214) cycles, non-conception (n = 132) versus conception (n = 82) cycles, and ongoing pregnancy (n = 66) versus early pregnancy loss (n = 16) groups. There was no correlation between LH serum levels in non-cancelled cycles and parameters of ovarian response and assisted reproduction treatment outcome. ROC analysis showed that serum LH concentration during ovarian stimulation was unable to discriminate between cancelled and non-cancelled cycles, conception versus non-conception cycles, or early pregnancy loss versus ongoing pregnancy groups. CONCLUSIONS: Serum LH measurements during ovarian stimulation with recombinant FSH under pituitary suppression in normogonadotrophic women undergoing assisted reproduction treatment cannot predict ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy. Thus, there is little underlying physiological support for the addition of LH in stimulation protocols if daily doses of an appropriate GnRH agonist (leuprolide or triptorelin having lower potency than buserelin) and a step-down regimen of recombinant FSH administration are used.     

Serum müllerian-inhibiting substance in Down's syndrome pregnancies

BACKGROUND: To examine whether maternal serum levels of müllerian-inhibiting substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS: Case-control study was conducted using stored serum from an antenatal screening programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20 degrees C storage together with 125 unaffected controls individually matched for maternal age, weeks of gestation and duration of storage. Results were expressed in multiples of the gestation-specific median value (MoM) in controls. RESULTS: The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically significant correlation between MIS and pregnancy-associated plasma protein-A (P < 0.05). MIS levels were elevated in pregnancies where assisted reproduction techniques had been used. CONCLUSION: There is no evidence for a substantial reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study provides useful information regarding serum MIS levels in pregnancy.     

The value of serum levels of oestradiol, progesterone and beta-human chorionic gonadotrophin in the prediction of early pregnancy loss.

Serial serum levels of oestradiol, progesterone and the beta-subunit of human chorionic gonadotrophin (beta-HCG) had been performed in 674 cycles in women conceiving a singleton pregnancy, either spontaneously or as a result of assisted conception. To determine the value of these estimations in the prediction of early pregnancy loss, frequency distribution curves and receiver operating characteristic curves were derived for the respective hormones measured at weeks 4-7 of gestation and expressed as multiples of the median (MoM) values in pregnancies occurring both with and without ovarian stimulation. A cut-off level of beta-HCG less than 0.5 MoM gave a sensitivity of 68% with an odds ratio of 4.0 at 7 weeks in unstimulated cycles in the prediction of pregnancy failure. A cut-off of 0.8 MoM for progesterone gave a sensitivity of 59% and an odds ratio of 2.8. Prospective hormonal monitoring during the early weeks of gestation may be useful in the prediction of early pregnancy loss and should help to avoid the emergency presentation of some of the complications of early pregnancy, in particular ectopic pregnancy. The limitations imposed by multiple pregnancies and uncertain gestation due to menstrual data may restrict the use of this strategy to specialist fertility centres.     

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.     

Maternal serum inhibin levels in twin and singleton pregnancies conceived by assisted reproduction

BACKGROUND: To investigate whether second trimester serum inhibin levels differ in pregnancies conceived by assisted reproduction technology (ART). METHODS: In Israel, serum samples from twin pregnancies were obtained for inhibin testing from women either referred for routine ultrasound monitoring, follow up after multi-fetal reduction or amniocentesis, largely for advanced maternal age. In the UK, inhibin had been tested prospectively in singleton and twin pregnancies of women having routine Down's syndrome (DS) screening. Results were available from 207 ART pregnancies: 170 singletons and 37 twins. This includes 15 twins from Israel, known to have been reduced from triplets to twins. Comparison was made with 4384 spontaneous pregnancies: 4334 singletons and 50 twins. Results were expressed in multiples of the gestation-specific median (MoM) for normal spontaneous pregnancies. RESULTS: In ART singletons, the median maternal inhibin level was higher (1.11 MoM) than in spontaneous singletons (0.99 MoM, P < 0.001, two-tail Wilcoxon Rank Sum Test). In twins, there was no material difference between ART and spontaneous pregnancies with medians of 1.98 and 2.18 MoM, respectively (P = 0.62). There was no effect of multi-fetal reduction, with medians of 1.76 and 1.81 MoM in reduced and non-reduced twins, respectively (P = 0.46). CONCLUSION: It appears that serum inhibin levels are increased on average in ART singletons but not in ART twin pregnancies. More data will be needed before deciding whether risk calculation parameters need to be altered when using inhibin for DS screening in pregnancy.     

Cryopreserved oocytes of infertile couples undergoing assisted reproductive technology could be an important source of oocyte donation: a clinical report of successful pregnancies

BACKGROUND: Surplus oocytes in assisted reproduction treatment cycles could be saved and donated to other couples. ICSI is usually performed for oocytes that have been stored frozen, considering possible exocytosis of cortical granules (CG). The unavoidability of ICSI merits further study. METHODS: We used a slow method to freeze excess oocytes from infertile couples. After thawing, oocytes were fertilized by either IVF or ICSI according to semen parameters. Some oocytes were examined for CG. RESULTS: Twenty-eight infertile couples cryopreserved a proportion of their oocytes and 12 thawed their oocytes. Three couples used their own oocytes, whereas nine donated their oocytes to nine other couples for 12 cycles. The survival rate from thawing was 90% (73/81). The fertilization rate using IVF (83%) was similar to ICSI (82%). Seven pregnancies (47% per cycle) were achieved; one used her own oocytes and six received donated oocytes. Five women delivered six babies including one set of twins. Two pregnancies aborted. The frozen-thawed oocytes (15/15) revealed no exocytosis of CG. CONCLUSIONS: To freeze oocytes of infertile couples undergoing assisted reproduction treatment may help other couples. Our successful experience may facilitate oocyte banks to become a reality. Both IVF and ICSI are valuable for frozen oocytes.     

Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization.

There is increased risk of early pregnancy loss after assisted reproduction. In this study the use of serum human chorionic gonadotrophin (HCG) concentrations on day 12 after in-vitro fertilization (IVF) and embryo transfer was evaluated to predict pregnancy outcome. A total of 417 IVF pregnancies were included. Early pregnancy loss was defined as biochemical pregnancies, ectopic pregnancies and first trimester abortions. Vital pregnancies were defined as delivered singletons, multiple pregnancies and second trimester abortions. On the post embryo transfer day 12, the mean HCG concentration of the vital pregnancy group was significantly higher than in early pregnancy loss outcomes (P < 0.00001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value of HCG giving maximal sensitivity and specificity in order to discriminate early pregnancy losses from vital pregnancies. A patient with a HCG value higher than the calculated cut-off value (55 IU/l) had a 90% chance of having a vital pregnancy after IVF and embryo transfer. It can be concluded that a discriminatory HCG value on day 12 after IVF and embryo transfer cycles may be useful in predicting pregnancy outcome and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population.