Maternal C-reactive protein levels are raised at 4 weeks gestation

BACKGROUND: The aim of this study was to determine whether there is evidence of a systemic maternal inflammatory response in very early pregnancy. METHODS: Successive women receiving treatment by IVF or ICSI had serum C-reactive protein (CRP) levels measured on the day of their pregnancy blood test at 4 weeks gestation (14 days post-egg collection). Women with positive betaHCG levels had ongoing pregnancies confirmed by serial transvaginal ultrasound scans up to 8 weeks gestation. RESULTS: Pregnant women (n = 40) were significantly younger (mean age 34 years) than women who failed to become pregnant (n = 95, mean age 37 years, P < 0.001), received significantly lower treatment doses of recombinant FSH (2000 versus 2400 IU, P < 0.05) and had significantly more eggs collected (11 versus 8, P < 0.01). There were no significant differences in body mass index, parity, a history of smoking, endometriosis or polycystic ovaries, pre-treatment CRP levels and white cell counts, peak serum estradiol levels and numbers of embryos transferred. Pregnant women had significantly higher CRP levels (median 3.68 mg/l) than those who were not pregnant (median 1.495 mg/l, P < 0.0001), a difference that persisted after excluding potential confounding variables. Six pregnant women with ovarian hyperstimulation syndrome had higher CRP levels than those who did not (P < 0.01). CONCLUSIONS: This well-controlled study is the first to demonstrate that maternal CRP levels are raised as early as 4 weeks gestation and thus that the maternal inflammatory response is established during the earliest phases of implantation. It is hypothesized that an abnormal response (either exaggerated or absent) could cause some cases of miscarriage.     

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.     

Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial

BACKGROUND: The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF. METHODS: Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used. All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test. The study group (n = 150) withdrew vaginal progesterone from the day of positive HCG. The control group (n = 153) continued administration of vaginal progesterone during the next 3 weeks of pregnancy. RESULTS: The number of miscarriages prior to and after week 7 of gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and 13 (8.5%) in the control group respectively. The number of deliveries was 118 (78.7 %) in the study group and 126 (82.4 %) in the control group. The differences were not significant. CONCLUSIONS: Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate, and thus no effect on the delivery rate. Progesterone supplementation can safely be withdrawn at the time of a positive HCG test.     

Improved sensitivity and specificity of a single measurement of serum progesterone over serial quantitative beta-human chorionic gonadotrophin in screening for ectopic pregnancy.

The sensitivity and specificity of a single serum progesterone measurement was compared against two beta-human chorionic gonadotrophin (HCG) measurements 48 h apart in screening for abnormal pregnancy, i.e. ectopic pregnancy, completed or incomplete abortion. Of 1120 patients in the first trimester presenting with a positive urinary pregnancy test, 116/1120 (10.4%) had an ectopic pregnancy, 755/1120 (67.4%) had ultrasonographically confirmed intra-uterine pregnancies, and 249/1120 (22.2%) had abnormal intra-uterine pregnancies documented as complete, incomplete or missed abortions. Of the ectopic pregnancies, 113/116 (97.4%) had a serum progesterone level less than 25 ng/ml while 516/755 (68.3%) viable intra-uterine pregnancies had a serum progesterone level greater than or equal to ng/ml. Of the 1120 patients screened, 402 (35.9%) had both a serum progesterone and two HCG measurements and were eligible for inclusion in this study. Setting a cut-off of 25 ng/ml, the sensitivity and specificity of a single serum progesterone measurement was then compared against two serial HCG measurements, utilizing receiver operating characteristic curves. This analysis demonstrated that a single serum progesterone measurement was significantly more sensitive (P less than 0.05) than two HCG measurements in screening for an abnormal pregnancy. In some patients, a single serum progesterone makes possible the diagnosis of ectopic pregnancy 2 days earlier than two HCG determinations because a second blood sample was not required. We conclude that a single serum progesterone measurement should be added to serial HCG determinations as a standard diagnostic screening test for ectopic pregnancy.     

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH

BACKGROUND: It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. METHODS: A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. RESULTS: The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. CONCLUSIONS: Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.     

Is intracytoplasmic sperm injection (ICSI) a safe procedure? What do we learn from early pregnancy data about ICSI?

The aim of this study was to evaluate the safety of the intracytoplasmicsperm injection (ICSI) procedure by analysing early pregnancydata from ICSI and in-vitro fertilization (IVF) patients. Inall, 50 ICSI pregnancies were compared with 226 FVF pregnancies.Comparisons were made during the first 9 weeks after the theoreticallast menstrual period (7 weeks after oocyte retrieval) withregard to epidemiological data, plasma hormonal concentrationsand transvaginal ultrasonographical findings. Although patientswere significantly (P < 0.001) younger in ICSI (31 years)than in IVF pregnancies (33 years), their duration of infertilitywas similar. Miscarriage and multiple gestation rates were notsignificantly different in ICSI pregnancies (respectively 24and 24%) from those found after IVF (32 and 29%). The probabilityof developmental arrest of the intrauterine sac (miscarriagesand vanishing twins) was similar in both ICSI (16%) and IVF(25%) cases. The mean plasma hormonal concentrations startingfrom day 11 after oocyte retrieval were similar in both groups.Every ICSI and IVF pregnancy showed an embryo with cardiac activityat 7 weeks. Early pregnancy data did not show any abnormal findingsfor pregnancies achieved using ICSI compared to those achievedby FVF.     

Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone

This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.     

Obstetric outcome of pregnancies after the transfer of cryopreserved and fresh embryos obtained by conventional in-vitro fertilization and intracytoplasmic sperm injection.

This study reports the obstetric outcome of pregnancies obtained after the transfer of cryopreserved or fresh embryos where the initial procedure was standard in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Pregnancies obtained after frozen IVF (n = 245) or frozen ICSI (n = 177) were compared with a control group of pregnancies after fresh embryo transfer in standard IVF (n = 245) and ICSI (n = 177) cycles were selected as controls. The controls were matched according to maternal age, parity and date of embryo transfer. In the standard IVF group, the biochemical pregnancy rates in the cryopreserved and fresh groups were 18.8 and 9.8% respectively (P < 0.01). In the ICSI group, the biochemical pregnancy rates in the cryopreserved and fresh groups were 16.4 and 6.8% respectively (P < 0.01). The miscarriage rates were comparable between the cryopreserved and fresh groups. However, in the frozen ICSI group the miscarriage rate (26.0%) was significantly higher than in the frozen conventional IVF group (13.1%) (P = 0.001). The frequencies of preterm deliveries, infants with very low birthweight and intrauterine deaths were similar in the groups. The low birthweight rates in the frozen IVF (16.1%) and ICSI (12.1%) groups were significantly lower than those in the fresh IVF (32.2%) and ICSI (32.7%) groups (P < 0.001). The major malformation rates in the frozen IVF (2.4%) and ICSI (2.9%) groups were not different from the major malformation rates in the fresh IVF (4.5%) and ICSI (2.4%) groups. In conclusion, the cryopreservation process had no negative impact on the outcome of pregnancies over 20 weeks of gestation. Long-term follow-up studies are needed in order to prove the safety of the freezing-thawing process.     

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.     

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.     

Single progesterone assay for early recognition of abnormal pregnancy

Serum progesterone and human chorionic gonadotrophin (HCG) were analysed using a time-resolved fluoroimmunoassay in an unselected group made up of 158 women with clinical suspicions of abnormal early gestation. Only cases in which endovaginal sonography had failed to localize the pregnancy were included. A single HCG determination had no diagnostic value. On the other hand, a critical progesterone level of 30 nM was determined below which no viable intrauterine pregnancies were found. Eighty-eight per cent of the ectopic pregnancies (n = 97) and 83% of the spontaneous abortions had progesterone levels below this limit. The discriminatory efficacy of one single progesterone determination was independent of the actual HCG level and serial determinations of progesterone did not increase the discriminatory power.     

Andrology: Successful treatment of severe male factor infertility in 100 consecutive cycles using intracytoplasmic sperm injection

In this report, we present the results of our first 100 consecutivecycles of intracytoplasmic sperm injection (ICSI). Overall,fertilization occurred in 98% of cycles and embryos were transferredin 94% (2.6 embryos per cycle). About 50% of patients had embryosfrozen. The overall fertilization rate was 71%, of which 4%were abnormally fertilized (three pronuclei). A total of 30clinical pregnancies were established (32% per transfer), resultingin 18 singleton, six twin and one triplet ongoing pregnancies.The implantation rate per embryo was 15%. There were no significantdifferences in the fertilization or pregnancy rates betweenpatients Who had only occasional motile spermatozoa in the ejaculate,semen that was too poor for routine in-vitro fertilization (IVF),or who had failed routine IVF and/or subzonal sperm injection(SUZI). A group of 18 patients were treated with both ICSI androutine IVF on their first cycle because of the high likelihoodof failed fertilization due to poor sperm morphology (<20%normal). In this group, ICSI oocytes had a fertilization rateof 76% compared to only 15% for the routine IVF (control) oocytes,and six patients conceived after transfer of ICSI embryos (33%),indicating that ICSI can be used successfully on 50% of theoocytes if fertilization failure is expected. Similarly, patientswho had failed to become pregnant with SUZI achieved excellentresults after ICSI. There were no significant differences betweenICSI and routine IVF in the proportions of grade 1, 2 or 3 embryoson day 3 post-oocyte recovery. In conclusion, we have achievedresults comparable to those reported from Belgium and we havefound that ICSI is universally applicable to all forms of severemale factor infertility. ICSI produces fertilization, pregnancyand freezing rates comparable to routine IVF with normozoospermicsamples and has none of the drawbacks of other assisted fertilizationtechniques.     

Decreased serum levels of macrophage migration inhibition factor in miscarriages with normal chromosome karyotype

BACKGROUND: The aim of this study was to determine serum concentrations of macrophage migration inhibition factor (MIF) during normal pregnancies, and to assess whether serum MIF concentrations early in pregnancies predict the subsequent outcome in women with recurrent miscarriage (RM). METHODS: Serum MIF concentrations were measured by ELISA. Sera were collected from normal women in the first (Group I, n = 29), second (Group II, n = 25) and third trimester (Group III, n = 26) and from 78 RM women at 4-6 weeks gestation. Eleven of these 78 pregnancies subsequently ended in first trimester miscarriage with normal fetal chromosome karyotype (MsNK), seven ended in first trimester miscarriage with abnormal karyotype (MsAK), and three ended in biochemical pregnancy. The other 57 pregnancies ended in live birth (LB) between 32-41 weeks gestation, and only one woman developed preeclampsia. RESULTS: Median MIF concentrations in Group I, II and III were similar at 17.6, 16.4 and 15.1 ng/ml respectively. MIF concentrations during early gestation in RM women with subsequent MsNK, MsAK and LB were 8.1, 11.4 and 16.4 ng/ml respectively. MIF concentrations in RM women with MsNK were significantly lower than those in RM women with LB (P < 0.01) and than those in Group I (P < 0.01), II (P < 0.05) and III (P < 0.05). CONCLUSIONS: Decreased serum MIF concentrations during early gestation were found in RM women with MsNK, and might be related to the aetiology of miscarriage.     

Progesterone supplementation increases luteal phase endometrial thickness and oestradiol levels in in-vitro fertilization.

Luteal phase supplementation with natural progesterone appears to increase the pregnancy rate in in-vitro fertilization (IVF). The objective of this investigation was to examine the effect of intravaginal progesterone on endometrial thickness and hormonal parameters 7-9 days after embryo transfer. IVF patients receiving progesterone supplementation (Prog +, n = 64), who did not conceive, were compared to patients not receiving progesterone (Prog -, n = 23) because of failed fertilization. These two groups were also compared to 20 women (Preg) who conceived and to 16 women (control) in the mid-luteal phase of natural cycles. Endometrial thickness was greater (P < 0.01) in the Prog + (0.88 +/- 0.04 cm) and Preg (0.92 +/- 0.02 cm) groups compared to the Prog - (0.71 +/- 0.05 cm) and control (0.65 +/- 0.05 cm) groups. Mean luteal phase serum oestradiol levels were also higher (P < 0.05) in the Prog + (1118 +/- 112 pmol/l) and Preg (2267 +/- 757 pmol/l) groups than in the Prog - (574 +/- 70 pmol/l) and control (468 +/- 38 pmol/l) groups. These findings suggest that progesterone supplementation may affect pregnancy rates in IVF by increasing endometrial thickness, thereby enhancing receptivity for implantation. The mechanism through which this effect occurs is unclear but may involve serum oestradiol elevation.     

Maternal and neonatal outcomes in dichorionic twin pregnancies following IVF treatment: a hospital-based comparative study

Aim: To compare maternal, and neonatal outcomes in IVF/ICSI and spontaneously conceived dichorionic twin pregnancy. Method: We collected data regarding dichorionic twin pregnancies following in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI, n=162) with the transfer of fresh embryos as well as data regarding spontaneously conceived pregnancies (n=213) delivered after 28 weeks of gestation at the Department of Obstetrics and Gynecology, Renmin Hospital in Wuhan in the years of 2010-2013. We then compared maternal and neonatal outcomes between IVF/ICSI and spontaneous dichorionic twin pregnancies, with a subgroup analysis separating traditional IVF from ICSI pregnancies. Odds ratios (OR) for associations between IVF/ICSI and pregnancy outcomes were adjusted for maternal factors. Results: The mean maternal age and the percentage of primiparous women were significantly higher in the IVF/ICSI group. Multivariate analysis revealed that maternal outcomes were comparable in both groups with/without adjustment for maternal age and parity. However, IVF/ICSI twins were less likely to have birth weight discordance than those spontaneously conceived (unadjusted OR=0.526, 95% CI 0.297-0.932; adjusted OR=0.486, 95% CI 0.255-0.856). In subgroup analyses, these associations were confirmed in the IVF (adjusted OR=0.496, 95% CI 0.265-0.926), but not in the ICSI group (adjusted OR=0.500, 95% CI 0.139-1.807). Conclusion: IVF/ICSI treatment was not a risk factor for adverse maternal neonatal outcomes, but the risk for birth weight discordance is lower among IVF/ICSI twins.     

Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur either as an early (early onset) or a late pattern (late onset). This observational study was designed to identify whether the onset pattern of OHSS is associated with the occurrence of pregnancy and the early pregnancy outcome. METHODS: Among 4376 consecutive IVF/ICSI cycles, 113 patients were hospitalized for OHSS after IVF/ICSI treatment and were included in the study. The setting was the Dutch-speaking Brussels Free University Hospital, between June 2000 and September 2002. RESULTS: Early OHSS occurred in 53 patients, and late OHSS complicated 60 patients. A total of 96.7% of the late OHSS cases occurred in a pregnancy cycle and were more likely to be severe than the early cases (P < 0.05). Although in the early group there initially was a 41.5% positive HCG rate per cycle, the clinical pregnancy rate fell to 28.3% as a result of a significantly (P < 0.05) increased preclinical pregnancy loss rate compared with the non-OHSS patients (31.8 versus 88.3%, respectively). The ongoing pregnancy rate per cycle was 14.4% in the early and 26.4% in the late group. Multiple pregnancy rates were high in both groups (40 and 45.5%, respectively), but only in the late group did the incidence reach significance compared with the non-OHSS population (45.5 versus 29.1%, P = 0.02). Estradiol levels and number of follicles on the day of HCG were significantly higher in the early OHSS group. However, there was no difference in estradiol values on the day of hospital admittance between the two groups. In addition, the number of follicles on the day of HCG administration appears to be a better prognostic indicator for the occurrence of severe OHSS than the estradiol values (87% of the severe cases had > or = 14 or follicles of a diameter > or = 11 mm, whereas only 50% of them had an estradiol value > or = 3000 ng/l). CONCLUSIONS: The early OHSS pattern is associated with exogenously administered HCG and a higher risk of preclinical miscarriage, whereas late OHSS may be closely associated with the conception cycles, especially multiple pregnancies, and is more likely to be severe. Further clarification of these two different clinical entities could have implications for research protocols as well as for preventive and management strategies for OHSS.     

Pregnancy: The expectant management of early pregnancies of uncertain site

The role of expectant management was evaluated in 80 women inwhom clinical examination, including vaginal ultrasound, hadfailed to identify the location of an early pregnancy. In 45cases, spontaneous resolution of the pregnancy products occurred.A normal intra-uterine pregnancy was diagnosed in 12 patients.A total of 23 patients underwent active therapeutic measuresdue to an ectopic pregnancy (n = 16) or a spontaneous abortion(n = 7). The effectiveness of different diagnostic measuresto identify patients suitable for expectant management was analysed.In 33/34 patients (97%) with a relative daily human chorionicgonadotrophin (HCG) change of <–5%, and a serum progesteroneconcentration of <20 nmol/l, spontaneous resolution of thepregnancy products occurred. Among 46 cases, with a relativedaily HCG change of >–5% and/or serum progesterone>20 nmol/l, active therapeutic measures were carried outin 22 cases (48%), a normal intra-uterine pregnancy was diagnosedin 12 cases (26%) and spontaneous resolution of the pregnancyproducts occurred in 12 cases (26%). In conclusion, the combinationof a single progesterone assay and serial HCG determinationsretrospectively identified early pregnancies of uncertain locationin whom expectant management was a safe management option.     

Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.     

Maternal serum beta-HCG and alpha-fetoprotein concentrations in singleton pregnancies following assisted reproduction

BACKGROUND: The reason for the elevated levels of HCG in assisted reproduction pregnancies remains unknown. Our hypothesis was that this increase is caused by the ovarian superovulation therapy. METHODS: We compared the beta-HCG and alpha-fetoprotein (AFP) multiples of the median (MoM) in singleton pregnancies after IVF or ICSI with those achieved by frozen embryo transfer (FET) in spontaneous cycles. RESULTS: The HCG and AFP MoMs (plus minus SEMs) of 59 FET pregnancies were compared with 144 IVF (including 48 ICSI) pregnancies. The maternal HCG of pregnancies following ovarian stimulation was 1.31 plus minus 0.08 MoM compared with 1.35 plus minus 0.12 MoM in the unstimulated ones. The values for AFP were 1.06 plus minus 0.05 versus 1.11 plus minus 0.05 respectively. No significant differences could be observed between pregnancies following stimulated IVF/ICSI and unstimulated FET cycles. CONCLUSIONS: Our results show that second trimester maternal serum HCG is also elevated in singleton pregnancies following spontaneous FET cycles. The increased maternal serum HCG in IVF pregnancies is thus not related to superovulation therapy. Because of the elevated maternal serum HCG levels, serum screening cannot be performed reliably in pregnancies following assisted reproduction technology. Ultrasonographic detection of the nuchal translucency is unaffected and should be used for this group of women undergoing assisted reproduction.     

Predictive value of a single serum pregnancy associated plasma protein-A or progesterone in the diagnosis of abnormal pregnancy

The value of a single measurement of serum levels of pregnancy associated plasma protein-A (PAPP-A) or progesterone (P4) in predicting abnormal gestations was assessed in 65 patients. P4 was greater than 20 ng/ml (mean +/- SEM 61.2 +/- 6.6 ng/ml, range 22.4-100.0 ng/ml) in all patients with normal intrauterine pregnancies (n = 21), and greater than 20 ng/ml (mean +/- SEM 8.5 +/- 3.9 ng/ml, range 0.1-68.8 ng/ml) in 16 out of 17 patients destined to abort spontaneously. Patients with ectopic gestations (n = 27) exhibited P4 values less than 20 ng/ml (mean +/- SEM 6.4 +/- 1.2 ng/ml, range 0.1-17.2 ng/ml). P4 levels in normal pregnancies were significantly higher (P = 0.001) than those of abnormal gestations. PAPP-A levels ranged from undetectable to 6448 mIU/ml in normal gestations. In 42 out of 44 abnormal pregnancies levels of PAPP-A were less than 100 mIU/ml, as were 7 out of 14 normal intrauterine pregnancies of less than 7 weeks gestational age. No ectopic demonstrated a value of PAPP-A greater than 50 mIU/ml and in 23 out of 27 ectopics, levels were undetectable. However, PAPP-A was less specific than P4 in correctly discriminating normal from abnormal gestations and exhibited lower positive and negative predictive values. It can be concluded therefore that a single PAPP-A measurement is of limited value in discerning normal from abnormal pregnancy prior to 8 weeks gestation. However, a single serum P4 is highly accurate and specific in detecting abnormal pregnancy, regardless of gestational age.