Chorionic Gonadotropin Concentrations Research Articles

False-Negative Pregnancy Test in Hydatidiform Mole

A 16-year-old girl (gravida 0, para 0) presented to the emergency department with a 2-week history of nausea, vomiting, vaginal spotting, and lower leg edema. On examination we found a palpable lower abdominal mass. The patient acknowledged recent sexual activity but denied having any sexually transmitted diseases. Molar pregnancy was suspected because of the typical “snowstorm” appearance observed with ultrasound examination. The quantitative serum β-subunit of human chorionic gonadotropin (β-hCG) concentration was 746.20 IU/L (reference interval, <0.5 to 2.90 IU/L; reportable interval, 0.5–1000 IU/L). The result of a qualitative urine hCG test, however, was negative. Human error was initially suspected as the cause of the negative result in the first qualitative urine hCG test. Two experienced and well-trained senior medical technologists repeated the urine hCG test twice, but the results were still negative. The patient’s nurse also indicated that she did not think there had been mislabeling of the urine sample. Because of this discrepancy, we …

Effects of chorionic gonadotropin on peripheral monocytes vary with the phases of the menstrual cycle

The qualitative and quantitative effects of physiological concentrations of chorionic gonadotropin (CG) on monocytes of women vary with the phases of the menstrual cycle. During the follicular phase, the hormone inhibits phagocytosis; stimulates the secretion of interleukin (IL) 6 (IL-6), interferon α (IFN-α), and the protein component of apolipoprotein A1 (APO-A1); and activates myeloperoxidase (MPO). During the luteal phase, CG stimulates phagocytosis and APO-A1 secretion, inhibits MPO, and does not shift the levels of IL-6 and INF-α. Regardless of the menstrual phase, the hormone does not modify the release of elastase or the production of granulocytic colony-stimulating growth factor, IL-1α, and tumor necrosis factor α.

Dose-related actions of GnRH II analog in the cycling rhesus monkey

Introduction Gonadotropin-releasing hormone (GnRH) II expression, specific high-affinity receptors for GnRH II and its potent bioactivity in human and baboon tissues led us to hypothesize that GnRH II is a bioactive peptide in primates. We recently demonstrated the contraceptive activity of GnRH II analog in rhesus monkeys. In the present experiment, we extended those studies to the dose-related action of this analog on parameters of luteal function and conception. Methods GnRH II analog (0–32 μg/day) or saline was administered via osmotic minipumps for 6 days (Days 1–6 postovulation) to regularly cycling rhesus monkeys mated with fertile males around the time of ovulation. Cycle dynamics was monitored through circulating luteinizing hormone, progesterone and estradiol. Pregnancy was determined by circulating chorionic gonadotropin concentrations. Results Progesterone production (Days 3–11) was significantly less (p<.05) for animals treated with 2, 4 or 8 μg/mL GnRH II analog than for controls, yet with higher doses of GnRH II analog (i.e., 16 or 32 μg/day), luteal progesterone was not different from that of saline-treated controls. The length of the luteal phase in all treated groups was similar to that of controls. In 18 animals mated at the time of ovulation and then treated with GnRH II analog (2–32 μg/day), no pregnancies resulted. In saline-treated controls, five of eight animals (62.5%) became pregnant. Thus, the contraceptive activity of this GnRH II analog did not correlate with luteal progesterone inhibition. Conclusions These data demonstrate a dose-related action of GnRH II analog on luteal progesterone and establish the contraceptive activity of 2–32 μg/day GnRH II analog administered postovulation.

Suspected Ectopic Pregnancy

Women who present with pain and bleeding in the first trimester are at risk for ectopic pregnancy, a life-threatening condition. Conditions that predispose a woman to ectopic pregnancy are damaged fallopian tubes from prior tubal surgery or previous pelvic infection, smoking, and conception using assisted reproduction. Many women without risk factors can develop an ectopic pregnancy. A diagnostic algorithm that includes the use of transvaginal ultrasonography, human chorionic gonadotropin (hCG) concentrations, and, sometimes, uterine curettage can definitively diagnose women at risk in a timely manner. The absence of an intrauterine pregnancy above an established cut point of hCG is consistent with an abnormal pregnancy but does not distinguish a miscarriage from an ectopic pregnancy. When the initial hCG value is low, serial hCG values can be used to determine whether a gestation is potentially viable or spontaneously resolving. The minimal rise in hCG for a viable pregnancy is 53% in 2 days. The minimal decline of a spontaneous abortion is 21-35% in 2 days, depending on the initial level. A rise or fall in serial hCG values that is slower than this is suggestive of an ectopic pregnancy. Women diagnosed with an unruptured ectopic pregnancy are potential candidates for medical management with methotrexate. Intramuscular injection with methotrexate can be used to safely treat an ectopic pregnancy with success rates, tubal patency rates, and future fertility that are similar to those obtained with conservative surgery. Success rates using methotrexate are inversely rated to baseline hCG values and are higher using "multidose" compared with "single-dose" regimens. Surgical treatment may be conservative or definitive and should be attempted in most cases via laparoscopy.

Serum oestradiol and β-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome

The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and β-human chorionic gonadotrophin (HCG-β) concentration 12 days after embryo transfer (D12HCG-β) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-β were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP ( P ≤ 0.001). For D3 embryo transfers, the cut-off value of D8E2 in predicting OP was 130 pg/ml (sensitivity 80%, specificity 72%), compared with 98 mIU/ml (sensitivity 89%, specificity 69%) for D12HCG-β. For D5 embryo transfers, the values were 179 pg/ml (sensitivity 79%, specificity 84%) and 257 mIU/ml (sensitivity 78%, specificity 81%) respectively. It appears that serum post-embryo transfer D8E2 and D12HCG-β concentrations provided clear information regarding pregnancy and the outcome of pregnancy following IVF–embryo transfer.

Progesterone and equine chorionic gonadotropin concentrations around the time of pregnancy loss in mares impregnated by donkeys or stallions

The objective of this study was to compare the incidence of pregnancy loss of mares carrying a mule embryo with that of mares carrying a horse embryo. The possible causes of such mortality were evaluated through serial ultrasonographic evaluations and hormonal monitoring, paying special attention to the role of premature regression of the endometrial cups and its relation to inadequate luteal function. Twenty-eight mares impregnated by stallions and 19 mares impregnated with donkey semen were evaluated ultrasonographically every week from day 20 to day 150 of pregnancy. The viability of the product was assessed each time, and the diameter of the embryonic vesicle was measured from day 25 to day 60. Blood samples for progesterone and equine chorionic gonadotropin (eCG) determination were taken every week. Both progesterone and eCG concentrations during normal pregnancies wegre significantly lower in the mares inseminated with donkey semen than in the mares impregnated by stallions (P<.05). In 7 of the mares carrying mule conceptuses to term, the concentrations of eCG remained basal throughout the study. In the other animals from this group, the levels of this hormone did increase but returned to baseline much earlier (on day 77 of pregnancy) than in the mares served by stallions (on day 126 day of pregnancy). There was no significant difference between the growth rate of embryonic vesicles of mares carrying mule embryos and that of mares carrying horse embryos (P>.05). The incidence of pregnancy loss was significantly higher (P<.05) in mares carrying a mule embryo (36.8 %) than in mares carrying a horse embryo (21.4%); it occurred on average on day 93 of pregnancy in mares carrying mule embryos and on day 43 on mares carrying horse embryos. There was only 1 case in which pregnancy loss was associated with concentrations of both eCG and progesterone that were much lower than the average for the normal pregnancies of the same group, and this was in a mare carrying a horse embryo. The most frequent cause of pregnancy loss was premature luteal regression due to primary luteolysis, as evaluated via peripheral progesterone concentrations. This occurred in 2 mares carrying horse embryos and in 4 mares carrying mule embryos. Three mares carrying mule embryos and 1 carrying a horse embryo had abortions that were not preceded or accompanied by any alteration in progesterone or eCG levels and were thus classified as fetal deaths of non-endocrine origin. It is concluded that the incidence of pregnancy loss is higher in mares carrying a mule embryo than in mares carrying a horse embryo. However, this is not due to the low progesterone concentrations associated with the premature regression of the endometrial cups that occurs in mares with interspecific pregnancy.

Diagnosis and treatment of ectopic pregnancy.

Ectopic pregnancy is a life- and fertility-threatening condition that is commonly seen in Canadian emergency departments. Increases in the availability and use of hormonal markers, coupled with advances in formal and emergency ultrasonography have changed the diagnostic approach to the patient in the emergency department with first-trimester bleeding or pain. Ultrasonography should be the initial investigation for symptomatic women in their first trimester; when the results are indeterminate, the serum beta human chorionic gonadotropin (beta-hCG) concentration should be measured. Serial measurement of beta-hCG and progesterone concentrations may be useful when the diagnosis remains unclear. Advances in surgical and medical therapy for ectopic pregnancy have allowed the proliferation of minimally invasive or noninvasive treatment. Guidelines for laparoscopy and for methotrexate therapy are provided.

Specificity and promiscuity of gonadotropin receptors

The dichotomy between hormone recognition by the ectodomain and activation of the G protein by the rhodopsin-like serpentine portion is a well established property of glycoprotein hormone receptors. The specificity barrier avoiding promiscuous activation of the FSH receptor by the high concentration of human chorionic gonadotropin (hCG) prevailing during human pregnancy was thus believed to lie in the ectodomain. In the past two years, mutations responsible for rare spontaneous cases of ovarian hyperstimulation syndromes have partially modified this simple view. Five naturally occurring mutations have been identified which cause an increase in the sensitivity of the FSH receptor to hCG. Surprisingly, these mutations are all located in the serpentine portion of the receptor. In addition to their effect on sensitivity to hCG, they increase sensitivity of the FSH receptor to TSH, and are responsible for activating the receptor constitutively. Together, the available information indicates that the ectodomain and the serpentine domain of the FSH receptor each contribute to the specificity barrier preventing its spurious activation by hCG. While the former is responsible for establishment of binding specificity, the latter introduces a novel notion of functional specificity. Recent data demonstrate that LH and FSH receptors can constitute functional homo- and heterodimers. This suggests the possibility that in cells co-expressing the two receptors, such as granulosa cells, the heterodimers might be endowed with functional characteristics different from those of each homodimer.

Increased maternal serum human chorionic gonadotropin concentrations are an independent risk factor for SGA in dichorionic twin gestations

Objective. To determine maternal and neonatal complications among dichorionic and monochorionic twins with isolated midtrimester elevated maternal serum human chorionic gonadotropin (MShCG).Material and methods. MShCG was determined in 247 women with dichorionic twins and 32 women with monochorionic twins between 16–18 weeks gestation. Among the dichorionic twins 219 patients had MShCG < 2.5 MoM, 14 between 2.5–3.0 MoM and 14 above 3.0 MoM. Of the patients with monochorionic twins 15 had MShCG < 2.5MoM, nine between 2.5–3.0 MoM and 8 above 3.0 MoM. All patients had maternal serum α fetoprotein < 2.5 MoM. Karyotype was normal among all neonates. Statistical analysis was performed with SPSS package.Results. Patients with monochorionic twins had higher rates of cesarean section when MShCG was > 3.0 MoM (100% vs. 44%; p = 0.03) and of preterm delivery when MShCG was > 2.5 MoM (87.5% vs. 46.7%; p = 0.04). A non significant higher rate of small for gestational age (SGA) neonates was found when MShCG was > 2.5 MoM among first twin (37.5% vs. 13.3%; p = 0.08). In contrast, patients with dichorionic twins had higher rates of SGA neonates and low 1 minute Apgar scores in the second twin when MShCG was > 2.5 MoM (23.1% vs. 10%; p = 0.04, 15.4% vs. 11.9%; p < 0.01). A multivariate logistic regression model with forward stepwise selection was performed with SGA as outcome variable. The model included the following variables: MShCG, hypertensive disorders, gestational age at delivery, chorionicity, twin order, cesarean section (CS) and preterm delivery. MShCG levels were the only significant factor predicting SGA among bichorionic twins (OR 1.76, 95% CI 1.2–2.5).Conclusions. (1) Increased concentrations of MShCG are an independent risk factor for SGA among dichorionic twins. (2) MShCG > 2.5 MoM are associated with adverse maternal outcome among monochorionic twins.

Effects of the ovulatory serum concentration of human chorionic gonadotropin on the incidence of ovarian hyperstimulation syndrome and success rates for in vitro fertilization

To determine whether the serum concentration of hCG on the day after hCG administration (abbreviated throughout this article as [hCG]) is related to the incidence of ovarian hyperstimulation syndrome (OHSS), oocyte recovery per follicle, fertilization, blastulation, embryo transfer, implantation, and clinical pregnancy. Retrospective study. Private infertility clinic. The OHSS study group included 849 non-donor IVF cycles performed between January 1998 and August 2003. The study group for hCG efficacy included 248 nondonor IVF cycles performed between January 2001 and May 2003 with patients younger than 35 years of age. None. Occurrence of OHSS, severity of OHSS, [hCG], proportion of follicles yielding oocytes, fertilization rate, blastulation rate, transfer rate, implantation rate, and clinical pregnancy rate. No significant relationships were observed between [hCG] and the proportion of follicles yielding oocytes, fertilization rate, blastulation rate, or the probabilities of embryo transfer, implantation, or clinical pregnancy. The incidence of OHSS (all types) and OHSS requiring transvaginal paracentesis were predicted by [hCG] (P=.02 and P=.05, respectively) and with follicle count (P<.0001 in both cases). These results suggest that moderated hCG dosage is useful in preventing OHSS without reducing efficacy.

Overdiagnosis of Complete and Partial Hydatidiform Mole in Tubal Ectopic Pregnancies

Partial or complete hydatidiform mole (HM) affects approximately 1 in 500 to 1,000 pregnancies. Previous small series suggest that histopathologic diagnosis of HM may be difficult in tubal ectopic pregnancies. The histopathology database of a regional Trophoblastic Disease Unit was searched to identify cases with a referral diagnosis of tubal HM, and the histopathologic findings were reviewed. During the study period (1986-2004 inclusive), there were 132 cases. After central review by specialist histopathologists, the final diagnosis was ectopic partial mole in two, ectopic complete mole in five, and ectopic hydatidiform mole (not otherwise specified) in one. The final diagnosis of definite hydatidiform mole was made in eight (6%) cases, significantly less than in referred uterine curettage specimens, in which approximately 90% have a confirmatory diagnosis of HM (Z = 12.9; p < 0.0001). No cases in this series developed persistent gestational trophoblastic disease, the human chorionic gonadotropin concentration spontaneously returning to normal. Ectopic pregnancies, where managed surgically, should be submitted for histopathologic examination; however, the pathologist should be aware that the degree of extravillus trophoblastic proliferation may appear more florid compared with evacuated uterine products of conception. Molar pregnancy should only be diagnosed when strict criteria regarding morphologic abnormalities previously described in uterine evacuation material are applied.

A case of simultaneous tubal-splenic pregnancy after assisted reproductive technology

To present a case of simultaneous splenic and tubal pregnancy following in vitro fertilization. Case report. University hospital. A 37-year-old woman who had undergone in vitro fertilization and embryo transfer for unexplained infertility at another clinic. Laparoscopy and laparotomy. Serum concentration of human chorionic gonadotropin (hCG) after salpingosplenectomy. After transfer of three embryos following fertilization by intracytoplasmic sperm injection (ICSI) at another clinic, the patient was referred to our hospital with suspicion of ectopic pregnancy. Because tubal pregnancy was suspected, laparoscopic right salpingectomy was performed. Although villi were detected in the resected fallopian tube, the serum hCG concentration did not decrease after the operation and a new intraabdominal hemorrhage was detected. We then suspected abdominal pregnancy in the epigastric region, and performed magnetic resonance imaging, computed tomography, and ultrasound examinations, which revealed implantation at the inferior pole of the spleen. Splenectomy was performed, with the resulting disappearance of intraabdominal hemorrhage and rapid fall of the serum concentration of hCG. Assisted reproduction sometimes results in heterotopic pregnancy, but an abdominal pregnancy involving the upper abdominal organs is considered extremely rare. Particularly, splenic pregnancy is usually overlooked and may only be discovered after a sudden intraabdominal hemorrhage. If hemorrhaging is present in the abdominal cavity but pregnancy is not detected within the pelvis, it is advisable to examine patients using imaging techniques to detect any upper abdominal pregnancies.

Lack of correlation between elevated maternal serum hCG during second‐trimester biochemical screening and fetal congenital anomaly

Isolated elevations in midtrimester maternal serum human chorionic gonadotrophin concentrations (MShCG) have been reported to be associated with a substantially increased likelihood of fetal congenital malformations. The reported malformations included a wide range of organ systems, originating at different embryologic developmental stages. The purpose of our study was to determine the significance of an isolated elevated MShCG (>2.5 MoM) in midtrimester for the detection of fetal structural anomalies in a large population. Among 10,144 women who underwent a biochemical triple screen at 15 to 18 weeks' gestation, 463 patients, who had an elevated MShCG, but normal alpha-fetoprotein (AFP) and unconjugated estriol (uE3) levels, were identified. Patients with an integrated calculated Down syndrome risk above 1:250 were excluded. Only nonsmokers, at ages <35 years, without a history of prior fetal anomalies were included. The control group consisted of 463 patients with normal serum analyte concentrations and Down syndrome risks below 1:250, who were matched for maternal age and date of biochemical screen. All patients underwent a detailed genetic sonogram in which an anatomic survey and multiple 'soft markers' for aneuploidy were looked for. Newborns were examined by a senior pediatrician trained in dysmorphology. MShCG levels were 3.18 +/- 0.72 versus 0.99 +/- 0.43 MoM (p < 0.0001) in study and control groups respectively. Sonography revealed 8 versus 6 cases of major congenital anomalies among the 463 patients of their respective groups, and 39 versus 36 sonographic 'soft markers' for aneuploidy. Fetal karyotyping and neonatal examination for dysmorphology revealed 6 chromosomal anomalies (4 Down syndrome; 2 Turner syndrome) among the 8 major malformations in the study group, but none in the controls (p < 0.0001). Three of the 39 fetuses with 'soft markers' and elevated MShCG were found to have trisomy 21. Isolated elevation of MShCG does not confer an increased risk of fetal congenital anomalies other than chromosomal abnormalities. However, elevated MShCG levels in combination with sonographic 'soft markers' for aneuploidy were associated with a high incidence of chromosomal anomalies, despite a normal biochemical triple screen risk estimate.

Effects of supra‐physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscle

The purpose of this study was to investigate the effects of supra-physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo-physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross-sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17beta-oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30+/-0.29, 1.16+/-0.38, 1.20+/-0.29 and 1.26+/-0.34 N mm-2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33+/-0.20 N mm-2 at week 12 of pregnancy, 1.51+/-0.42 N mm-2 at week 20, 1.15+/-0.26 N mm-2 at week 36 and 0.94+/-0.31 N mm-2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force-generating capacity of young women.

The Carboxyterminal Peptide of Chorionic Gonadotropin Facilitates Activation of the Marmoset LH Receptor

Luteinizing hormone (LH) and chorionic gonadotropin (CG) are heterodimeric glycoprotein hormones acting on the luteinizing hormone receptor (LHR). In the LHR, which is genomically encoded by eleven exons, exon 10 encodes for the hinge region and its elimination impairs LH action, while CG maintains normal activity. The two gonadotropins differ in the carboxyterminal peptide (CTP) present in CG but absent in LH. Since the marmoset monkey (Callithrix jacchus) LHR naturally lacks exon 10 (LHR type II), we generated two recombinant marmoset gonadotropin preparations, one consisting of the wild type CG and one of truncated CG lacking the CTP (CG (-CTP)). After calibration in a mouse Leydig cell bioassay against the WHO LH80/522 standard, the ED (50) of the CG preparation on a COS7 cell line permanently expressing the marmoset LHR was 4.25 +/- 0.21 IU/L (n = 3). Stimulation of the COS7 cell line with equipotent concentrations of CG and CG (-CTP) resulted in significantly different formation of cAMP (two-way ANOVA, p < 0.001). In particular, cAMP production stimulated by CG (-CTP) was 3 - 4 times lower compared to CG at the saturating CG concentration (8 IU/L). We conclude, supplementing one current model of LHR activation, that exon 10 might play a permissive role in releasing the constraint of the receptor upon hormone binding, resulting in receptor activation. We speculate that, when exon 10 is lacking, the CTP can overcome its absence and facilitates the opening of the receptor, resulting in normal activation.

Historical Perspectives

This month’s Historical Perspectives is in a slightly different format, but should be of considerable interest to readers of NeoReviews. Professor Nicholas Wald is an epidemiologist who has evaluated and written about a variety of topics, but he is best known for his work on screening methods, particularly in the area of maternal serum alpha-fetoprotein (AFP) and fetal abnormalities. Because of his continuing heavy commitments and to minimize the disruption of his schedule, I posed a number of questions to him, to which he responded with detailed answers. Before moving to his responses, some background information seems in order. Shortly before publication of the article highlighted this month, evaluation of amniotic fluid in cases of open spina bifida and other neural tube defects had shown increased levels of AFP. (1) Somewhat later, it was shown that abdominal wall defects, as well as neural tube defects, could contribute to increased levels of amniotic fluid AFP. (2) In his responses, Professor Wald documents the sequence of events that followed, noting that Professor David Brock in Edinburgh described the association of increased levels of maternal serum alpha-fetoprotein (MSAFP) with fetal anencephaly, which triggered the idea that this also might be true of open spina bifida. Thus, MSAFP was used as a screening tool for the detection of neural tube and abdominal wall defects. Elevated MSAFP levels were noted in other “at-risk” pregnancies (3) and twin pregnancies. (4) To provide better standardization, Professor Wald introduced the concept of “multiples of the median” (MoM) at different gestational ages. Approximately a decade passed before the association was made between low MoMs for AFP and chromosomal defects, particularly Down syndrome. Soon thereafter, several other serum markers for Down syndrome were described, and by linking them to maternal age, screening became increasingly valuable. In the early 1980s, Dr …

Elevated midtrimester maternal serum hCG is not associated with fetal congenital anomalies unrelated to chromosomal anomalies

Isolated elevations in midtrimester maternal serum human chorionic gonadotropin concentrations (MShCG) have been reported to be associated with a substantially increased likelihood of fetal congenital malformations (Fejgin et al., 1997). Malformations included a wide range of organ systems, originating at different embryologic developmental stages. We investigated the significance of an isolated elevated MShCG (>2.5 MoM) for the detection of fetal structural anomalies.

Increasing hCG concentrations during storage at +4°C with the Bayer Centaur Total hCG method

The interpretation of changes in serum human chorionic gonadotropin (hCG) concentrations in early pregnancy requires a knowledge of the day-to-day imprecision of the method at the concentrations measured. We therefore attempted to determine the analytical imprecision of our total hCG method over a 4-week period at concentrations up to 20,000 IU/L. Serum specimens with hCG concentrations between 100 and 20,000 IU/L were collected during early pregnancy and analysed using the Bayer Centaur Total hCG method at weekly intervals after storage at (+)4 degrees C and (-)20 degrees C. The reproducibility of hCG results over a 4-week period in refrigerated specimens with an initial hCG concentration below 1000 IU/L was poor (mean coefficient of variation = 17.4%) and there was an apparent increase in serum hCG concentrations of up to 68%. Similar changes occurred in some specimens stored at (-)20 degrees C. Further experiments confirmed that significant increases can occur during the first week following specimen collection. Total hCG concentrations in serum specimens collected during early pregnancy increase significantly during storage when measured by the Bayer Centaur Total hCG method, possibly due to a conformational change in hyperglycosylated hCG. When this method is used for monitoring early pregnancy, specimens should ideally be analysed on the day of collection.

Livebirth after orthotopic transplantation of cryopreserved ovarian tissue

The lifesaving treatment endured by cancer patients leads, in many women, to early menopause and subsequent infertility. In clinical situations for which chemotherapy needs to be started, ovarian tissue cryopreservation looks to be a promising option to restore fertility. In 1997, biopsy samples of ovarian cortex were taken from a woman with stage IV Hodgkin's lymphoma and cryopreserved before chemotherapy was initiated. After her cancer treatment, the patient had premature ovarian failure. In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy. 5 months after reimplantation, basal body temperature, menstrual cycles, vaginal ultrasonography, and hormone concentrations indicated recovery of regular ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and showed the presence of a follicle at the site of reimplantation, clearly situated outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the patient had menstrual bleeding and development of a follicle or corpus luteum with every cycle. 11 months after reimplantation, human chorionic gonadotrophin concentrations and vaginal echography confirmed a viable intrauterine pregnancy, which has resulted in a livebirth. We have described a livebirth after orthotopic autotransplantation of cryopreserved ovarian tissue. Our findings suggest that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.

First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: A population-based screening study (The FASTER Trial)

The purpose of this study was to determine whether maternal serum levels of pregnancy-associated plasma protein A, free-beta subunit human chorionic gonadotropin, or nuchal translucency size are associated with obstetric complications. Data were obtained from the First and Second Trimester Evaluation of Risk trial. Pregnancy-associated plasma protein A and free-beta subunit human chorionic gonadotropin levels were analyzed, and nuchal translucency was measured between 10 weeks 3 days and 13 weeks 6 days of gestation in 34,271 pregnancies. Women with pregnancy-associated plasma protein A of < or =5th percentile were significantly more likely to experience spontaneous fetal loss at < or =24 weeks of gestation, low birth weight, preeclampsia, gestational hypertension, preterm birth ( P < .001) and stillbirth, preterm premature rupture of membranes, and placental abruption ( P < .02). Nuchal translucency at > or =99th percentile and free-beta subunit human chorionic gonadotropin at < or =1st percentile were associated with an increased risk of spontaneous loss at < or =24 weeks of gestation (adjusted odds ratios, 3.90, 3.62, respectively; P < .001). Low pregnancy-associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free-beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss.