hCG Pregnancy Research Articles

The reproductive outcome of rescue ICSI cycles with a complete fertilization failure after in vitro fertilization insemination is conditioned by the number of oocytes reinseminated

The reproductive outcome of rescue ICSI cycles with a complete fertilization failure after in vitro fertilization insemination is conditioned by the number of oocytes reinseminated

Urine Pregnancy Testing in Two Women with Cancer

Questions1. What are the most striking clinical and laboratory findingsin these patients?2. Why is it important to assess pregnancy status?3. What are some of the causes of false-positive serum andurine pregnancy tests?4. How would you rule out human or technical error as a possiblecause of a false-positive or -negative urine pregnancy test?5. What can cause discordances between urine and serum hCGtest results?6. What is the most likely diagnosis for these patients?7. What is the clinical significance of a false-positive urinepregnancy test?8. Are serum hCG tests unaffected by factors that can causefalse-positive test results?Possible Answers1. The most striking laboratory findings in both of thesepatients was a positive urine pregnancy test in patients who,based on their medical history (data not shown), were not ex-pected to have a positive urine hCG pregnancy test.2. Determination of pregnancy status is important in thework-up of a woman presenting with vaginal bleeding or lowerabdominal pain. Women with these symptoms should bescreened for pregnancy using a urine pregnancy test, especiallyprior to undergoing an x-ray procedure. Clinical decisions re-garding additional diagnostic testing should be based on the re-sults of the urine pregnancy test and knowledge of thoseconditions that can cause false-positive screening tests for humanchorionic gonadotropin (hCG) in urine and serum, includingthe presence of serum human anti-mouse antibodies (HAMA)and diseases (eg, colon or cervical cancer) associated with excre-tion of hCG into the urine.3. A number of preanalytical conditions, other than preg-nancy, including trophoblastic disease and certain non-trophoblastic neoplasms (eg, testicular tumors, prostate cancer,breast cancer, and lung cancer), can cause elevated serum levelsof hCG that are then excreted into the urine.

Quantification of urinary chorionic gonadotropin in spontaneous abortion of pre-clinically recognized pregnancy: Method development and analytical validation

Determination of environmental impacts on reproductive health and specifically on the incidence of early spontaneous abortion requires accurate estimates of the latter. This negative reproductive outcome can be detected by the pattern of elevation and decline of human chorionic gonadotropin (hCG) levels near and shortly beyond the expected time of implantation, requiring daily biomonitoring of hCG levels during the relevant period of the menstrual cycle. Prospective pregnancy studies to assess effects of potentially toxic exposures on human reproductive outcomes can involve up to three menstrual cycles and a huge number of samples in each, for the quantification of the inherently very low hCG levels usually can be determined only in serum. The invasive nature of blood collection, the number of samples needed for the development of prospective studies, and the lack of quantitative methods for the determination of low hCG levels in urine point to the need for collecting urine rather than blood and make it imperative to develop suitable quantitative methods for biomonitoring of very low levels of hCG in urine. This paper describes the development and validation procedures of an automated solid-phase two-site chemiluminescent immunometric assay for the quantification of urinary hCG in early pregnancy and early pregnancy loss. For the validation, both undiluted and diluted urine and control samples have been prepared. From the results, it can be concluded that the assay has a calibration range that extends to 5000 mIU/ml, with a detection limit of approximately 1.2 mIU/ml, practically identical to that found by the IMMULITE 2000 manufacturer's validation study. The intra- and inter-assay precision ranges up to a maximum of around 7%, meaning that the practical limit for functional sensitivity can be established as low as 10%. This means that the immunoassay from DPC ® can identify, with relatively high confidence, non-pregnant women and the typical “rise and fall” pattern of early pregnancy loss through analysis of urine samples. Results also lead to the conclusion that there is a very good agreement between expected and observed urinary hCG levels indicative of good immunoassay accuracy for the studied range of hCG concentrations. In terms of analyte stability, it can be concluded that urinary hCG is stable under the expected conditions required for ongoing investigations that include temperatures of 2–8 °C for up to 48 h and temperatures of around −20 °C for longer periods that can extend to over 3 months.

Hourly human chorionic gonadotropin secretion profiles during the peri-implantation period of successful pregnancies

To characterize the hourly profiles of hCG secretion in blood during conceptive cycles that ended in successful pregnancy. Prospective study. University fertility clinic and research laboratories. Healthy spontaneously ovulating women with regular menses, no history of infertility, and either no male partner or an azospermic partner. Frequent blood samples were collected daily from 11 spontaneously ovulating women during 11 cycles of artifical insemination with donor semen. The concentrations of hCG, LH, and FSH were measured in the blood by immunoassay. The concentration of hCG in the frequent blood samples and the rate that the concentration of hCG changed during the period of frequent sampling. For the conceptive cycles resulting in successful pregnancies analyzed, hourly hCG concentrations were observed to increase in a consistent nonpulsatile manner. These data provide the first characterization of the hourly secretion profile of hCG in early pregnancy as well as provide further evidence that individual daily blood samples are sufficient for the accurate assessment of pregnancy.

Serum levels of interleukin-6, interleukin-1β and human chorionic gonadotropin in pre-eclamptic and normal pregnancy

Studies in placentas from the first trimester and in vitro models indicate that interleukin (IL)-1β and IL-6 induce the release of human chorionic gonadotropin (hCG). During pre-eclampsia there is an increase of pro-inflammatory cytokines; however, its relationship with hCG levels during the third trimester of pregnancy has not been determined. The aim of the present study was to evaluate the relationship between blood levels of IL-6, IL-1β and hCG in normal pregnancy and pre-eclampsia. Blood samples during the third trimester of pregnancy from women with severe pre-eclampsia (n = 20) or normal pregnancy (n = 20) were assayed for hCG by immunoassay, IL-6 and IL-1β by enzyme-linked immunosorbent assay. Serum level of IL-6 was significantly higher in pre-eclamptic than in normal women (16.5 ± 2.1 vs. 4.9 ± 1.1 pg/ml); however, IL-1β was similar in both groups. Although hCG was higher in pre-eclampsia than normal pregnancy, the difference was not statistically significant. Furthermore, IL-1β in normal pregnancy was correlated negatively with hCG (r = −0.69, p < 0.001). In conclusion, serum levels of IL-6 were increased in pre-eclampsia but were not correlated with hCG or IL-1β; however, in normal pregnancy there was a negative correlation between IL-1β and hCG. The interaction between IL-1β and hCG at the third trimester needs to be investigated.

Previous aneuploidy does not significantly alter 1st trimester free beta hcg and papp-a in subsequent normal pregnancies

ObjectiveTo investigate the influence of a previous aneuploid pregnancy on the screening values of a subsequent, normal gestation.Study designWeight and race adjusted free beta hCG and PAPP-A levels were compared in patients with previous aneuploid pregnancy. Data were analyzed using ANOVA of natural log(MOM) values. Significance was determined using Dunnett's procedure for all groups vs. control using a two-sided test at a significance level of 0.05. Dunnett's critical value was adjusted for unequal sample sizes.ResultsThe table shows the geometric mean and SD of natural log(MOM) for free Beta hCG and PAPP-A for each type of previous aneuploidy. The difference between the log(MoM) mean in each group and the “none” group in terms of standard errors was 2.28, 1.81, 2.66, 0.75 for free Beta hCG and 1.87, 2.51, 1.66, 1.82 for PAPP-A, in the previous trisomy 21, trisomy 18, trisomy 13 or 45,X groups, respectively. Dunnett's critical value for 4 groups and 36076 degrees of freedom is 2.61 so only free Beta hCG levels in previous Trisomy 13 were significant.ConclusionTabled 1Free Beta MoMPAPP-A MoMPrevious AneuploidyNGeom Mean (SD)Geom Mean (SD)None33,2260.99 (0.4972)1.00 (0.5675)Trisomy 211,7831.02 (0.5110)1.03 (0.5771)Trisomy 187961.02 (0.5100)1.05 (0.5694)Trisomy 131601.10 (0.5090)1.08 (0.6185)45, X1121.03 (0.4557)1.10 (0.5356) Open table in a new tab ObjectiveTo investigate the influence of a previous aneuploid pregnancy on the screening values of a subsequent, normal gestation. To investigate the influence of a previous aneuploid pregnancy on the screening values of a subsequent, normal gestation. Study designWeight and race adjusted free beta hCG and PAPP-A levels were compared in patients with previous aneuploid pregnancy. Data were analyzed using ANOVA of natural log(MOM) values. Significance was determined using Dunnett's procedure for all groups vs. control using a two-sided test at a significance level of 0.05. Dunnett's critical value was adjusted for unequal sample sizes. Weight and race adjusted free beta hCG and PAPP-A levels were compared in patients with previous aneuploid pregnancy. Data were analyzed using ANOVA of natural log(MOM) values. Significance was determined using Dunnett's procedure for all groups vs. control using a two-sided test at a significance level of 0.05. Dunnett's critical value was adjusted for unequal sample sizes. ResultsThe table shows the geometric mean and SD of natural log(MOM) for free Beta hCG and PAPP-A for each type of previous aneuploidy. The difference between the log(MoM) mean in each group and the “none” group in terms of standard errors was 2.28, 1.81, 2.66, 0.75 for free Beta hCG and 1.87, 2.51, 1.66, 1.82 for PAPP-A, in the previous trisomy 21, trisomy 18, trisomy 13 or 45,X groups, respectively. Dunnett's critical value for 4 groups and 36076 degrees of freedom is 2.61 so only free Beta hCG levels in previous Trisomy 13 were significant. The table shows the geometric mean and SD of natural log(MOM) for free Beta hCG and PAPP-A for each type of previous aneuploidy. The difference between the log(MoM) mean in each group and the “none” group in terms of standard errors was 2.28, 1.81, 2.66, 0.75 for free Beta hCG and 1.87, 2.51, 1.66, 1.82 for PAPP-A, in the previous trisomy 21, trisomy 18, trisomy 13 or 45,X groups, respectively. Dunnett's critical value for 4 groups and 36076 degrees of freedom is 2.61 so only free Beta hCG levels in previous Trisomy 13 were significant. ConclusionTabled 1Free Beta MoMPAPP-A MoMPrevious AneuploidyNGeom Mean (SD)Geom Mean (SD)None33,2260.99 (0.4972)1.00 (0.5675)Trisomy 211,7831.02 (0.5110)1.03 (0.5771)Trisomy 187961.02 (0.5100)1.05 (0.5694)Trisomy 131601.10 (0.5090)1.08 (0.6185)45, X1121.03 (0.4557)1.10 (0.5356) Open table in a new tab

P-299: Vaginal vs. abdominal ultrasound guidance for embryo transfer

ObjectiveCorrect placement of the catheter in the uterus during embryo transfer (ET) is essential for a successful outcome. Abdominal ultrasound is primarily utilized to visualize the catheter during embryo transfer. Vaginal ultrasound is generally utilized in instances when there is difficulty visualizing the catheter with the abdominal ultrasound. The objective of this study is to compare the efficacy of abdominal ultrasound and vaginal ultrasound for catheter placement in the uterus during embryo transfer.DesignA retrospective study in a private ART center.Materials and methodsAll fresh autologous and donor invitro fertilization (IVF) cycles performed between January 1, 2005 and December 31, 2005 resulting in ultrasound guided embryo transfer (n=779) were included in this study. All transfers were performed by a single physician. Group 1 (n=690) had abdominal ultrasound guided ET and Group 2 (n=89) had vaginal ultrasound guided ET. Cycles resulting in positive hCG (>5MIU/mL) and Clinical Pregnancy (CP) rates for each group were determined and compared.ResultsTable 1 illustrates the summary of our findings.Tabled 1* Not statistically significant using Chi Squared testConclusionWe can therefore conclude that both catheter visualization methods are acceptable for ultrasound guided embryo transfer. ObjectiveCorrect placement of the catheter in the uterus during embryo transfer (ET) is essential for a successful outcome. Abdominal ultrasound is primarily utilized to visualize the catheter during embryo transfer. Vaginal ultrasound is generally utilized in instances when there is difficulty visualizing the catheter with the abdominal ultrasound. The objective of this study is to compare the efficacy of abdominal ultrasound and vaginal ultrasound for catheter placement in the uterus during embryo transfer. Correct placement of the catheter in the uterus during embryo transfer (ET) is essential for a successful outcome. Abdominal ultrasound is primarily utilized to visualize the catheter during embryo transfer. Vaginal ultrasound is generally utilized in instances when there is difficulty visualizing the catheter with the abdominal ultrasound. The objective of this study is to compare the efficacy of abdominal ultrasound and vaginal ultrasound for catheter placement in the uterus during embryo transfer. DesignA retrospective study in a private ART center. A retrospective study in a private ART center. Materials and methodsAll fresh autologous and donor invitro fertilization (IVF) cycles performed between January 1, 2005 and December 31, 2005 resulting in ultrasound guided embryo transfer (n=779) were included in this study. All transfers were performed by a single physician. Group 1 (n=690) had abdominal ultrasound guided ET and Group 2 (n=89) had vaginal ultrasound guided ET. Cycles resulting in positive hCG (>5MIU/mL) and Clinical Pregnancy (CP) rates for each group were determined and compared. All fresh autologous and donor invitro fertilization (IVF) cycles performed between January 1, 2005 and December 31, 2005 resulting in ultrasound guided embryo transfer (n=779) were included in this study. All transfers were performed by a single physician. Group 1 (n=690) had abdominal ultrasound guided ET and Group 2 (n=89) had vaginal ultrasound guided ET. Cycles resulting in positive hCG (>5MIU/mL) and Clinical Pregnancy (CP) rates for each group were determined and compared. ResultsTable 1 illustrates the summary of our findings.Tabled 1* Not statistically significant using Chi Squared test Table 1 illustrates the summary of our findings. * Not statistically significant using Chi Squared test ConclusionWe can therefore conclude that both catheter visualization methods are acceptable for ultrasound guided embryo transfer. We can therefore conclude that both catheter visualization methods are acceptable for ultrasound guided embryo transfer.

P-254: No advantage of using the sequential GIII media versus the single media Global

The sequential media system is based on the concept of the different nutritional requirements of the pre-embryo prior to and post its third day of cell culture (Gardner and Lane, 1998, review). This logic has become the mainstream of the ART lab cell culture media system. The Global media is a modification of the KSOM media, which is based on the potassium simplex optimized calculation. Recently, Biggers and Racowsky (2002) reported on a one media culture system (KSOM + amino acids) that gave similar blastocyst formation rate as the sequential media (P1◊CCM). Using mouse embryos, Biggers, et.al., (2005), reported no significant difference of mouse embryo development and delivery rates between the one-step and two-step sequential culture system. This study intends to compare the performance of the sequential GIII media system with one-step Global media in a human ART trial. A ramdomized prospective study. The Global media was purchased from IVFonline.com, Guelph, Ontario, Canada. The GIII was purchased from Vitrolife, Englewood, Colorado, U.S.A.. With the help from Mr. Michael Baird, Vitrolife’s cell culture specialist, we were familiarized with the unique GIII media culture methodology sequence. All steps were followed to the exact standards. A total 60 cycles were randomly assigned, 30 to the GIII culture system, and 30 to the Global culture system. The criteria for inclusion in this prospective random study were patient age less than 40, and no PGD case (no embryo biopsy). The parameters of hCG pregnancy, ongoing pregnancy, and blastocyst formation rate were analyzed by the Chi-Square test. The GIII media culture system had more biochemical pregnancies while the Global media system had more SAB. Since the number is very small, it is impossible to derive any conclusion. The results did not show any significant trend in favor of any of the specified media systems.Tabled 1 In our system, and with our patient population, there was no advantage of the GIII media over the Global media. The results support Bigger’s conclusion that a 2-step sequential culture protocol is sufficient for the pre-implantation pre-embryo development, and that a one, correctly supplemented media, can also do a successful job throughout the entire length of the cell culture. Apparently, the pre-embryos have some flexibility in adjusting to variations of properly supplemented culture media.

Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study

To compare the clinical outcomes between letrozole and clomiphene citrate (CC) in gonadotropin-combined intrauterine insemination (IUI) cycles. Prospective pilot study. One university hospital and two private infertility clinics. Ninety-three infertile couples eligible for superovulation and IUI. A letrozole dose of 2.5 mg/day (n = 66) or a CC dose of 100 mg/day (n = 27) was given on day 3-7 of the menstrual cycle, combined with human menopausal gonadotropin (hMG) at a dose 150 IU every other day starting on day 5. The number of mature follicles, serum estradiol (E2) and progesterone (P) levels, endometrial thicknesses on the day of human chorionic gonadotropin (hCG), and clinical pregnancy rates. The patients' clinical characteristics were comparable between the two groups. The number of mature follicles (3.2 +/- 1.7 vs. 5.6 +/- 2.4) and serum E2 levels on the day of hCG (231.0 +/- 179.8 vs. 1,371.7 +/- 750.5 pg/mL) were significantly lower in the letrozole group. No significant differences were found in endometrial thickness measured on the day of hCG or clinical pregnancy rates (18.2% vs. 25.9%). The rate of patients with serum P levels > 1.0 ng/mL on the day of hCG was significantly lower in the letrozole group (4.5% vs. 25.9%). Letrozole produced a comparable pregnancy rate vs. CC in gonadotropin-combined IUI cycles. Our results should be confirmed in larger populations with proper randomization.

P-30: Reliability of Predicting Pregnancy Outcome Using Day 12 Serum hCG Following Emryo Transfer in ICSI-IVF Cycles

Objective: Correlation between serum HCG and pregnancy outcome has been the subject of great discussion. We aimed to evaluate the clinical value of a day 12 HCG level in patients undergoing in-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) in determining the final outcome. Unlike other studies that have reported early pregnancy HCG values in IVF patients with and without the ICSI protocol, this study aims at comparing values in patients that had undergone the ICSI procedure. Design: Retrospective analysis of patients undergoing assisted reproductive technologies at a single in-vitro fertilization center. Materials and Methods: A database containing 190 patients undergoing IVF with intracytoplasmic sperm injection resulting in pregnancy (day 12 HCG as reported by one single laboratory equal to or greater than 5) between January 1993 and February 2005 was analyzed. Pregnancies were categorized as chemical (no fetal pole), spontaneous abortion, ectopic, singleton, twin, and triplet. HCG and outcome information were retrieved from the charts. Results: 190 women met the minimum criteria. Database included 48 chemical pregnancies, 25 spontaneous abortions, 2 ectopics, 67 singletons, 38 twins and 10 triplets. Analysis of variance (ANOVA) test indicated that there was a significant difference between the groups (F-value=10.79, p<0.0001). Repeat ANOVA with the additional Duncan’s Multiple Range Test revealed no significant difference in the mean HCG levels of twins (200.8) versus singletons (160.94) or spontaneous abortions (170.13). There was a significant difference in the mean HCG levels of triplets (340.11) versus all other groups (sensitivity 30%, specificity 89%, positive predictive value 1.6%, and negative predictive value 84%). Conclusion: Day 12 HCG levels from a single laboratory do not reliably predict pregnancy outcomes in terms of spontaneous abortions, singletons or twins. They can however be used as a model to predict triplet pregnancies.

Defining the rise of serum HCG in viable pregnancies achieved through use of IVF

We aimed to characterize the rate of HCG rise associated with viable IVF pregnancies, and to evaluate the association between HCG rise and potentially influential factors. We performed a retrospective cohort analysis of all viable pregnancies achieved through IVF at two centres between January 1999 and March 2004. Of the 455 pregnancies resulting in live births, 391 met inclusion criteria and contributed a total of 1052 HCG values. Using random effects models, the best pattern to describe the rise of log HCG was quadratic with the rate of increase slowing at 24 days post-oocyte retrieval. Limiting the analysis to measurements below the discriminatory zone, the linear model adequately characterized the profile. The average slope was 0.403, yielding a predicted increase of 1.50 (50% increase) in 1 day and 2.24 (124%) in 2 days. In the final model, absolute HCG values, but not rate of rise, were significantly higher for twins and triplets and significantly lower for patients with BMI>30 kg/m2. The HCG profile of viable pregnancies conceived with IVF is quadratic with an earlier plateau than has been reported for non-IVF pregnancies. The average rate of rise is comparable to previous estimates in symptomatic spontaneous conceptions.

Additional Gonadotropin and Delayed Dosing of Gonadotropin-Releasing Hormone Antagonists (GnRH-ant) in Donor Oocyte Cycles Improves Outcomes

A reduction in serum estradiol (E2) seen in GnRH-ant cycles has been associated with adverse pregnancy outcomes. It is thought to be related to abnormal folliculogenesis and oocyte maturation. While some suggest luteinizing hormone supplementation improves clinical outcomes by maintaining E2, we evaluated the impact of additional follicle-stimulating hormone (FSH) and the timing of GnRH-ant on cycle stimulation in donor oocyte cycles. From 6/2000 to 4/2005, 93 initiated donor cycles resulting in 84 retrievals generated embryos for 123 recipient cycles (25 shared). All donors (27.0 ± 0.4 years (yr), ± standard error of the mean, range 19-36 yr) with normal day (d) 3 FSH (5.4 ± 0.3 mIU/mL) were placed on oral contraceptives for cycle synchronization. Following discontinuation, controlled ovarian hyperstimulation was begun following d3 of recombinant FSH (225 to 300 IUqd). GnRH-ant (Antagon, Organon) was begun on cycle d6 of ovarian hyperstimulation (Group A) or when lead follicles were 13-14 mm in greatest diameter (Group B) with an additional 75 IU of FSH/d. When lead follicles reached >18-20 mm diameter, human chorionic gonadotropin (hCG) (10,000 IU) was administered intramuscularly and transvaginal ultrasound guided aspiration was performed 36 hours later. All recipients (41.7 ± 0.6 yr, range 32-54 yr) were synchronized to the donors using GnRH-agonist down-regulation followed by estrogen and progesterone supplementation. Embryos were transferred transcervically 3 or 6 days post retrieval. Outcomes measured were days of stimulation (DOS), ampules (amp) used, E2 on d5 and day of hCG, oocytes retrieved, cancellation rates (CR), embryos transferred (ET), fertilization rates (FR), clinical and on-going pregnancy rates (PR) and implantation rates (IR). Categorical comparisons, analysis of variance and Bonferroni correction were used where appropriate. Two patterns of E2 were noted in A and B following GnRH-ant: a progressive rise in E2 (A1, n=22 and B1, n=26) or a decline in E2 (A2, n=21 and B2, n=24). B2 required significantly more FSH and DOS (45.7 ± 2.5 amp; 11.9 ±0.4 d) compared to A1 (35.3 ± 1.9 amp, 9.9 ± 0.3 d), A2 (41.2 ± 2.9 amp, 10.5 ± 0.3 d), and B1 (39.7 ± 2.2 amp, 11.2 ±0.4 d), p<0.006. No differences were seen in E2 on d5 of stimulation, but E2 on the day of hCG was lower in A2 (1256 ± 189 pg/mL) and B2 (1612 ± 239 pg/mL) compared to A1 (2154 ± 189 pg/mL) and B1 (2720 ± 289 pg/mL), p<0.006. No differences were seen with respect to CR and oocytes retrieved (A1: 0%, 21.5 ± 2.7; A2: 24%, 15.1 ±2.3; B1: 8%, 21.8 ± 2; B2 9%, 21.2 ± 2.5), p-NS. FR were similar with respect to the recipients for each group (A1 (n=30): 69% ± 4%; A2 (n=25): 80% ± 4%; B1 (n=34): 66% ± 5%; B2 (n=34) 68% ± 3%), p-NS. The number of ET was significantly less in B1 and B2 (2.7 ± .2 and 2.6 ± .2) compared to A1 and A2 (3.7 ± .2 and 4 ± .2), p<0.006. A2 had significantly lower clinical PR/ET (17%[4/24]) compared to A1 (61%[17/28]), B1 (48%[13/27]), and B2 (55%[16/29]); ongoing PR/ET (4%[1/24]) compared to A1 (57%[16/28]), B1 (44%[12/27]), and B2 (48%[14/29]) and IR (7%) compared to A1 (34%); B1 (39%), and B2 (43%), p<0.006. Increased FSH dosing and delayed GnRH-ant initiation did not enhance E2 production in donor oocyte cycles, though significant increases in clinical PR were seen regardless of the E2. This suggests that other gonadotropin factors may be pivotal for oocyte maturation and embryo development.

A Randomized Study of Recombinant Versus Urinary Human Chorionic Gonadotrophin in Chinese Women Undergoing Assisted Reproductive Technology Cycles

To compare the efficacy of recombinant human chorionic gonadotrophin (r-hCG) with that of urinary hCG (u-hCG) for triggering ovulation in patients undergoing assisted reproductive technology (ART) cycles. 217 patients undergoing ART in China were randomized (1: 1) to receive r-hCG or u-hCG to trigger ovulation. Infertile women between 21 and 35 years old with a BMI <25 kg/m2, with regular cycles of 25-35 days, received standard long-protocol downregulation. Recombinant follicle stimulating hormone (Gonal-f®, Serono) was started on day 3 of the cycle. When one follicle reached ≥18mm in diameter and at least 2 other follicles were ≥16mm, subjects were administered hCG (Ovidrel® freeze-dried 250mcg, Serono, subcutaneous or Profasi® 10000IU, Serono, intramuscular) on the next day. After 36 hours, oocytes were retrieved for in vitro fertilization. Up to 3 embryos were transferred. On day 14 of embryo transfer, serum hCG pregnancy test was conducted. Subjects with a positive test returned on day 30 for follow up. Progesterone was given for luteal phase support. The primary efficacy endpoint was the total number of oocytes retrieved. Other outcomes measured included the number of transferable embryos, and rates of implantation, clinical pregnancy and miscarriage. Chi-square test or Fischer’s Exact test were used for the analysis of categorical data and a two-sided t-test for continuous data. A similar number of oocytes were retrieved in the r-hCG group (14.91 ± 7.56; n=110), and the u-hCG group (15.37 ± 6.02; n = 107; p = ns). No significant difference between groups in terms of the number of mature oocytes retrieved (r-hCG: 14.16 ± 7.55; n = 109 vs u-hCG: 14.37 ± 5.51; n = 105), mean number of two pronuclei-fertilized oocytes (r-hCG: 9.50 ± 8.47, n=109 vs u-hCG: 9.51 ± 4.77, n = 107), transferable embryos (r-hCG: 8.35 ± 5.30; n=107 vs u-hCG: 8.24 ± 4.69, n=106), multinucleated blastomeres (r-hCG: 1.03 ± 1.61, n=107 vs u-hCG: 1.31 ± 1.70, n=105), or endometrial thickness on the day of oocyte retrieval (r-hCG: 10.71 ± 1.44, n = 110 versus u-hCG: 10.60 ± 1.39, n = 107) The mean concentrations of serum progesterone on the day of hCG and on Day 6 or 7 after hCG administration were similar between groups. There was a non-significant trend towards a higher pregnancy rate in the r-hCG group (biochemical pregnancy: 55/110, 50.0%; clinical pregnancy: 45/110, 40.9%) compared with the u-hCG group (biochemical pregnancy: 42/107, 39.3%; clinical pregnancy: 35/107, 32.7%). There was no significant difference in the number of multiple pregnancies in the r-hCG group (16/45, 35.5%) and the u-hCG group (13/35, 37.1%). There was a trend towards a lower miscarriage rate with r-hCG (9.3%) compared with u-hCG (19.0%), but this was not statistically significant. The safety of r-hCG was good and conform to the currently known profile of the product. A similar number of oocytes was retrieved in patients receiving r-hCG or u-hCG to trigger ovulation during ART procedures. However, there was a higher rate of clinical pregnancy and lower rates of miscarriage with r-hCG compared with u-hCG.

A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies

Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and is involved in establishing pregnancy by maintaining progesterone secretion from the corpus luteum. Serum hCG is detected in the maternal circulation within the first 2–3 wks of gestation and peaks at the end of the first trimester before declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly high compared to gestation age-matched uncompromised pregnancies. It has been proposed that increased serum hCG levels could be due to transcriptional hyper-activation of the CGB (hCG beta) gene, or an increased half life of glycosylated hCG hormone, or both. Another possibility is that serum hCG levels remain high due to reduced availability of the hormone's cognate receptor, LHCGR, leading to lack of hormone utilization. We have tested this hypothesis by quantifying the expression of the hCG beta (CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta (CGB) mRNA directly correlates with high serum hCG levels. The steady-state synthesis of LHCGR mRNA (exons 1–5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length LHCGR mRNA (exons 1–11) in DS was comparable to that of uncompromised pregnancies. However, the synthesis of high molecular weight mature LHCGR proteins was significantly reduced in DS compared to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG in DS pregnancies.

2nd-Trimester Maternal Serum Human Chorionic Gonadotropin and α-Fetoprotein Levels in Male and Female Fetuses with Down Syndrome

Background/Objective: Several studies have shown that the 2nd-trimester maternal serum α-fetoprotein (AFP) level is significantly lower and that the maternal serum human chorionic gonadotropin (hCG) level is significantly higher in the presence of a female fetus. This may potentially affect Down syndrome (DS) screening such that a higher false-positive rate may occur in women carrying a female fetus, whereas a lower detection rate may result in those carrying males. The purpose of this study was to evaluate the gender impact on marker levels in DS pregnancies and its effect on DS screening. Methods: The study included 62 DS pregnancies with a single fetus of known gender (31 male and 31 female). Only pregnancies with chromosomal analysis showing trisomy 21 were included. The maternal serum levels of hCG, AFP, and unconjugated estriol were measured at 16–20 weeks of pregnancy. These levels were expressed as gestational-age-corrected multiples of the median. Results: No statistically significant differences were noted in maternal serum levels of hCG or AFP in DS pregnancies between women carrying a female and those carrying a male DS fetus. No statistically significant differences in ‘screen-negative’ rates were noted among male and female fetuses. Conclusions: In normal pregnancies, the maternal serum hCG level is higher, and the AFP level is lower in the presence of a female fetus. However, this gender-related difference is not apparent in DS pregnancies. Therefore, the gender-related differences in serum marker levels would not result in a lower detection rate of DS in male fetuses.

Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review.

Evaluation of the association between estradiol (E2) levels on the day of hCG administration and pregnancy achievement in IVF has so far yielded conflicting results. The purpose of the present study was to systematically review the above association in cycles down-regulated with GnRH analogues. Literature search was performed using Medline, Embase (1978-2004) and the Cochrane Library. Additionally, references of retrieved articles were hand-searched. Only full articles published in peer-reviewed medical journals were considered for analysis. All the eligible studies (n=9) involved the use of GnRH agonists and were retrospective. Two studies (including 191 patients) suggested that the higher the E2 levels on the day of hCG administration, the higher the probability of pregnancy. However, five studies (including 1875 patients), did not support an association between E2 levels on the day of hCG administration and pregnancy rates. Moreover, two of the studies including (1286 patients) suggested that high E2 levels on the day of hCG administration are associated with a decreased probability of pregnancy. If we consider only studies in which criteria used for administering hCG include follicular development but not E2 levels (including 2687 patients), there is no study suggesting a positive association between E2 levels on the day of hCG administration and pregnancy achievement. Currently there is no high-quality evidence to support or deny the value of E2 determination on the day of hCG administration for pregnancy achievement in IVF cycles, where pituitary down-regulation is performed with GnRH agonists. Existing retrospective studies suggest that there is no positive association. However, in order to arrive at recommendations for clinical practice, there is a need to perform well-designed prospective studies in both agonist and antagonist cycles.

Missing date of last menstrual period: Impact on assessment of hCG for women at risk for an ectopic pregnancy

Describing the initial rise in hCG in early pregnancy is critical for the diagnosis of women at risk for ectopic pregnancy (EP). When date of last menstrual period (LMP) is unknown, the result is an undefined time axis for describing the profile. Estimates of expected rise, which can only be defined for the subset of subjects who have known LMP date, could potentially be biased. We utilize questionnaire data about the certainty of recall of LMP date to evaluate this bias in women ultimately diagnosed with a viable intrauterine pregnancy (IUP). Retrospective Cohort. Women presenting with pain/bleeding in first trimester of pregnancy, with no definitive diagnosis at first visit, were selected for study. Women were prospectively followed until establishment of a definitive diagnosis of IUP. At presentation, women were asked to classify their recall of LMP date as certain, uncertain, or unknown. The relationship between the hCG levels and LMP dates were modeled using regression methods that accommodate covariate measurement error. Of the 293 women who were ultimately diagnosed with IUP, 18.4 percent were uncertain or had unknown date of LMP. The 5 percent of women with no LMP information were assigned the average number of days since last LMP from the sample. Each category of LMP certainty was initially modeled separately. We found that the shape of the hCG profile for women of uncertain LMP was markedly similar to the profile derived from those women who were certain about the date. However, the amount of measurement error in the LMP values was much larger and dominated the profiles. This lead to very wide confidence bounds around the estimated hCG profiles. Thus, limiting their clinical relevance. Similar results were found using a single model for all the women, with varying errors for the certainty categories. While the measurement error in LMP was large, evaluation of hCG using the date of presentation (DP) for care as the time axis proved much more useful. Within the subset of women with known LMP, the slope for change in hCG determined using PD as the time axis was 0.402 95% CI (0.389,0.415) and gave similar result as using LMP which had slope 0.407 95% CI(0.395,04.19). Therefore, it is appropriate to make decisions about normal rise in hCG using PD. Many women who present with symptoms of pain and bleeding early in pregnancy are unsure of their LMP. The hCG rise of women with an IUP is very similar in those with certain or uncertain LMP. Estimating the LMP introduced far too much variability to be clinically useful. However, given that no bias in the estimated profile for hCG was detected for subjects with uncertain and unknown LMP we conclude that it is safe to use the date of presentation (and not LMP) to make decisions about hCG profiles for all women who present in early pregnancy who are at risk for EP.

Evaluation of prognostic value of CA125 serum levels in ICSI outcome

Introduction: Endometrial receptivity is an important factor in embryo transfer. CA125 is a recently considered glycoprotein that is produced by normal endometrium. There is a controversy about CA125 as an indicator of endometrial receptivity and a predictor of pregnancy. Settings: Vali-e-Asr Reproductive Health Research Center, Vali-e-Asr Hospital, TUMS. Materials and Methods: In this cross-sectional study, 120 intracytoplasmic sperm injection (ICSI) cases during March 2001–2002 were included. In addition to the assessment of association of variables with ICSI results, the prognostic value of CA125 serum concentration on the day of HCG administration and oocyte retrieval day was evaluated using an enzyme immunometric assay. Patients were divided in to two groups, pregnant and nonpregnant, based on transvaginal ultrasonography evaluation and were compared in terms of demographic and laboratory characteristics. The predictors of pregnancy were determined by using logistic regression model. Results: Pregnancy was obtained in 27 (22.5%) cycles. In the univariate analysis, the number of the transferred embryos ( P=0.007) and the serum levels of estradiol ( P=0.006) were significantly associated with pregnancy outcome. The mean levels of CA125≥16 IU/ml on the day of oocyte retrieval showed a marginally significant difference between pregnant and nonpregnant women ( P=0.05), but there was no significant association between serum levels of CA125 ≥10 IU/ml on the day of HCG administration and pregnancy outcome ( P=0.12). In the logistic regression model, the number of transferred embryos ≥3 (OR: 1.8, 95% CI: 1.2–2.8, P=0.01) and serum estradiol levels ≥1200 pg/ml (OR: 15, 95% CI: 3–76, P=0.023) were the only important predictors of pregnancy in ICSI. Conclusion: According to the multivariate analysis, serum CA125 levels cannot be used as predictor of pregnancy before embryo transfer in assisted reproductive technologies (ART) cycles.

Quinacrine sterilization (QS) in Syria: a preliminary report on 297 cases

Objectives: To evaluate the safety, efficacy and acceptability of quinacrine sterilization (QS) in Syria. Methods: From July 2001 to December 2002, 297 women who requested permanent sterilization volunteered for QS either in my private practice or my local family planning center in Aleppo, Syria. The standard protocol was used: 252 mg of quinacrine in the form of 7 pellets are deposited at the uterine fundus withy a modifeid CuT IUD inserter during the proliferative phase of the menstrual cycle. This procedure is repeated 4 weeks later. DMPA was injected at the time of the first insertion for temporary contraception. Every sterilized woman has had a monthly checkup visit until the cut-off date for this report, including a beta HCG pregnancy test. All procedures were performed by the author. The cut-off date for this report was June 11, 2003. Results: The single pregnancy was ectopic. Four women (1.3%) complained of severe pain. Moderate pain was experienced by 13.1% while the remaining women felt mild pain, all easily treated. The remaining side effects were minor and also easily treated. Oligomenorrhea and amenorrhea affected 29% of the women and lasted for several months. Immediate side effects are similar to reports from other researchers. Conclusions: Results thus far regarding efficacy are encouraging. QS has proven to be acceptable.

The use of recombinant (r) FSH in in vitro fertilization (IVF) may be associated with lower implantation rate

Objective: The objective of this study was the evaluation of rFSH versus purified urinary (u) FSH in a single IVF program involving all patients treated by a clinician and two embryologists and analysed by a multivariated approach. Design: A retrospective cohort analysis. Materials and Methods: The study included 425 consecutive cycles of IVF or ICSI, with at least one embryo transferred in women under the age of 40, down regulated under long or short protocol and stimulated to obtain high number of follicles. The only criterion for rFSH use was the coverage of medication from patient’s medical insurance. rFSH formulations were follitropin a or,. Factors analysed were: patient age, stimulation protocol, type of FSH, no. of eggs retrieved, no. of fertilized eggs, no. of transferred embryos. Cycle outcome factors were: increasing levels of serum hCG (pregnancy rate), heart beats (clinical pregnancy rate), implantation rate and delivery rate. The cycles were stratified in two groups, the rFSH group with 75 and the uFSH with 350 cycles. Univariated comparisons of all variables between the two groups were performed by ANOVA. Multivariated analysis was performed with all variables entering unconditionally into the model. Results: The mean age was similar in both groups, 33.4 in rFSH vs 32.7 years in uFSH. The mean no. of eggs retrieved and embryos obtained were 20.7 and 11.3 in rFSH vs 15.9 and 8.3 in uFSH groups (p=0.0001 and p=0.0000 respectively). The mean no of transferred embryos were similar, 4.3 in the rFSH vs 4.2 in the uFSH groups. In the rFSH group 37 cycles (49%) resulted in frozen spare embryos, significantly higher than those in uFSH 104 (30%), p=0.0001. Univariated analysis demonstrated similar outcome in both groups. Pregnancy, clinical pregnancy and delivery rates were 54.6%, 48.0% and 45.3% in rFSH vs 61.4%, 55.4% and 50.3% in uFSH groups. Miscarriages (9.3% in rFSH vs 12.0% in uFSH) and ectopics were similar in both groups. The rFSH group also presented a tendency towards lower implantation rate, 18.8 % vs 23.4% sacs/embryos (p=0.08) in the uFSH group. To eliminate confounding factors multivariated analysis was performed. Pregnancy was significantly correlated with the no. of availiable embryos (p=0.01) and the no. of transferred embryos (p=0.001). Delivery was significantly correlated with the age (p=0.004). Implantation rate was significantly correlated with the no. of availiable embryos (p=0.0001), negatively with the no. of transferred embryos (p=0.03) and negatively with the use of rFSH (p=0.03). Conclusion: The multivariated approach suggests that the use of rFSH in IVF correlates with higher no. of eggs retrieved, higher no. of embryos and higher no. of cycles with available frozen embryos. However, in terms of IVF outcome rFSH has no advantage over purified uFSH, possibly due to an underlying adverse effect of the use of rFSH on the endometrial receptivity.