Persistently expressed human chorionic gonadotropin induces premature luteinization and progressive alterations on the reproductive axis in female mice.

The hypothalamic-pituitary-gonadal axis plays a fundamental role in the endocrine regulation of the reproductive function in mammals. Any change in the function of the participating hormones or their receptors can lead to alterations in sexual differentiation, the onset of puberty, infertility, cancer development, and other dysfunctions. In this study, we analyzed the influence of persistently elevated levels of the human chorionic gonadotropin hormone (hCG), a powerful agonist of pituitary luteinizing hormone (LH), on the reproductive axis of female mice. As a consequence of chronic hCG hypersecretion through a global expression of the hCGbeta-subunit in transgenic (TG) female mice, a series of events perturbed the prepubertal to juvenile transition. The imbalance in gonadotropin action was first manifested by precocious puberty and alterations in gonadal hormone production, with the consequent ovarian function disruption and infertility in adulthood. The expansion of cumulus cells in vivo and in vitro, ovulatory capacity, and gene expression of ovulation-related marker genes after hormone stimulation were normal in 3-week-old TG females. However, the expression of genes related to steroidogenesis and luteinization such as Lhcgr, Prlr, and the steroidogenic enzymes Cyp11a1, Cyp17a1, and Cyp19a1 were significantly elevated in the TG females. This study demonstrates that the excessive secretion of hCG in concert with high prolactin, induced premature luteinization, and enhanced ovarian steroidogenesis, as was shown by the up-regulation of luteal cell markers and progesterone synthesis in the TG mice. Furthermore, progressively impaired reproductive function of the TG females occurred from the peripubertal stage to adulthood, thus culminating in infertility.

Case report: Two rare uterine cesarean scar mass cases.

RATIONALE: Gestational trophoblastic neoplasia (GTN) located in the cesarean scar is a rare disease that has imaging appearances similar to those of an exogenous scar incision pregnancy and is often misdiagnosed due to insufficient clinical experience. PATIENT CONCERNS: We report 2 cases of uterine cesarean scar mass. Two patients with different diagnoses had similar clinical complaints as abnormal vaginal bleeding, enlargement of uterus isthmus by physical examination, and mixed echo mass in uterine low segment by ultrasound examination; however, their magnetic resonance imaging images showed very different features. DIAGNOSES: One patient was diagnosed with cesarean scar pregnancy (CSP) and one patient was diagnosed with cesarean scar GTN. INTERVENTIONS: The CSP patient underwent surgery by laparoscopy combined with hysteroscopy after uterine artery embolism and obtained pathological confirmation. The GTN patient received chemotherapy. OUTCOMES: For the CSP patient, her serum ß-human chorionic gonadotropin (hCG) concentration returned to normal 2 weeks later, and B-ultrasound showed that the niche was completely repaired 3 months after the operation. The intrauterine lesions of the GTN patient disappeared completely 3 months after serum ß-hCG normalization. And her ß-hCG was normal at all follow-up visits until now. LESSONS: Clinicians should consider GTN when identifying masses at scar incision sites. Magnetic resonance imaging images improve the understanding of the imaging features in patients suspected of having CSP/GTN.

Characterization of beta subunit variants of recombinant human chorionic gonadotrophin.

Human chorionic gonadotropin (hCG), an endogenous glycoprotein hormone, has been widely used for the treatment of infertility and corpus luteum defect in women. The biological specificity of hCG is essentially determined by its beta (ß-) subunit, whereas the alpha (α-) subunit is a common subunit shared among the gonadotropin family. In development of a therapeutic recombinant hCG, the purity analysis showed that the beta (ß-) subunit has two variants, ß1 and ß2. Structural characterization using a combination of analytical techniques has demonstrated that ß1-subunit is derived from non-glycosylation at Asn 13, whereas ß2-subunit is a normal species with complete N-glycosylation at both Asn 13 and Asn 30. In vivo Bioactivity evaluation of the r-hCG fractions with various ratios of ß1-and ß2-subunits showed that incomplete glycosylation at Asn 13 potentially reduced the biological activity of r-hCG to promote uterus growth. Although hCG has a long history of medicinal use, this is the first report to identify the structural difference of hCG ß-subunit variants, as well as to preliminary establish the structure-activity relationship of this variation. The obtained results also suggest the importance of variant characterization and necessary quality control of product variants during the development of recombinant protein therapeutics.

The fertility sparing therapy in ectopic pregnancy.

OBJECTIVE: A review of current knowledge on the possibilities of fertility sparing therapy in case of ectopic pregnancy. METHODS AND RESULTS: Ectopic pregnancy is defined as implantation of an embryo outside the endometrial cavity, most often in the fallopian tube. This dia-gnosis is very common among young women. Ectopic pregnancies can be treated using the following three approaches, which can be combined: expectantly, pharmacologically or surgically. Fertility-sparing salpingostomy may be performed during surgical treatment. Medical (pharmacological) treatment consists in the application of methotrexate with a success rate of 75-96%, depending on the initial level of the free beta subunit of human chorionic gonadotropin (b-hCG). This is a safe treatment with minimal side effects. There is no standardization of the blood b-hCG level limits or of the size of the ectopic pregnancy mass for choosing expectant, surgical or medical treatment. A considerable increase in the rate of Cesarean sections over the last decades has led to an increase in the occurrence of the implantation of the gestational sac in the hysterotomy scar. There are several options to address this dia-gnosis, but none is clearly preferred. This issue is also discussed in the article. CONCLUSION: The goal of ectopic pregnancy treatment is to choose a safe and effective therapy with a low incidence of side effects and maintaining the maximum fertility of women. Properly set indication criteria are most important when choosing the right option.

Correlation between elevated maternal serum alpha-fetoprotein and ischemic placental disease: a retrospective cohort study.

BACKGROUND: To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD). METHODS: A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women's Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free ß-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups. RESULTS: The AFP MoM and free ß-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all P < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free ß-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group. CONCLUSIONS: Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.

Comparison of dual-trigger and human chorionic gonadotropin-only trigger among polycystic ovary syndrome couples who underwent controlled ovarian stimulation and intrauterine insemination: A retrospective cohort study.

The dual-trigger regime, consisting of gonadotrophin releasing hormone agonist and human chorionic gonadotropin (HCG), has been shown to offer advantage over the HCG-only trigger regime. However, little is known about the influence of dual-trigger or HCG-only trigger regime on the reproductive outcome of polycystic ovary syndrome (PCOS) couples undergoing controlled ovarian stimulation (COS) and intrauterine insemination (IUI). A total of 404 cycles of COS and IUI treatments from couples with PCOS were enrolled, and divided, according to the regime of trigger, into dual-trigger group (n = 109, 0.1-0.2 mg gonadotrophin releasing hormone agonist plus 6000 IU HCG) and HCG-only group (n = 295, 10,000 IU HCG or 250 µg recombinant HCG). Baseline characteristics of the 2 groups were comparable (all P > .05). In dual-trigger group, live birth rate, clinical pregnancy rate and ß -HCG positive rate were all higher as compared to the HCG-only group (20.18% vs 18.98%, 25.69% vs 23.39% and 28.44% vs 25.08% respectively), despite the differences failed to achieve statistical significances (all P > .05). Moreover, early miscarriage rate and multiple pregnancy rate of the dual-trigger group were lower than those of the HCG-only group (17.86% vs 18.84% and 3.57% vs 7.25% respectively), although no statistical significances were found (all P > .05). Additionally, logistic regression analysis revealed that age contributed significantly to the live birth of couples with PCOS ( P = .043, OR = 0.900). Dual-trigger regime for oocyte maturation seems to associate with beneficial improvements in reproductive outcomes of PCOS couples undergoing COS and IUI. Instead of HCG-only trigger, dual-trigger regime might be an alternative option in COS and IUI cycles for couples with PCOS.

The diagnostic value of transvaginal color Doppler ultrasonography plus serum ß-HCG dynamic monitoring in intrauterine residue after medical abortion.

To probe the diagnostic value of transvaginal color Doppler ultrasonography plus serum ß-human chorionic gonadotropin (ß-HCG) dynamic monitoring in intrauterine residue after medical abortion.In total, 200 pregnant women undergoing medical abortion in our institution from January 2017 to December 2019 were picked, and assigned to either group A (n = 75, with residue) or group B (n = 125, without residue). We detected serum ß-HCG, progesterone (P), follicle stimulating estrogen (FSH) levels and ultrasonic indicators endometrial thickness (ET), peak systolic velocity (PSV), resistance index (RI) values, dissected correlation of indicators using logistic linear regression analysis, and prospected the diagnostic value of relevant indicators in intrauterine residue after medical abortion utilizingreceiver operating characteristic curve.At 7 days after abortion (T3), total vaginal bleeding and visual analogue scalescore in group A were saliently higher in contrast to group B ( P < .05). At 72 hours after abortion (T2) and T3, serum ß-HCG, P and FSH levels declined strikingly in both groups, but group B held plainly higher decrease rate than group A ( P HC.05). At T3, ET and PSV levels in both groups considerably waned, whereas RI levels notedly waxed, and group B owned markedly higher decrease/increase than group A ( P wa.05). At T3, serum ß-HCG in group A possessed positive association with serum P, FSH, intrauterine ET, PSV levels separately ( P HC.05), whereas negative link with RI levels ( P , .05). The specificity and sensitivity of ß-HCG, P, FSH, ß-HCG/ET, ß-HCG/PSV and ß-HCG/RI in the diagnosis of intrauterine residue after medical abortion were high ( P < .05).Serum ß-HCG dynamic monitoring plus transvaginal color Doppler ultrasonography is of great value in diagnosing intrauterine residue after medical abortion. Serum ß-HCG, P, FSH levels can be combined with the results of intrauterine ET, PSV, RI values, so as to boost the diagnostic accuracy of the intrauterine residue after medical abortion.

Fibrin clot interference in a human chorionic gonadotrophin assay causing a false Down syndrome screening result.

Serum samples are generally used for the measurement of human chorionic gonadotrophin (hCG) to calculate second-trimester maternal screening results. Lower hCG concentrations correlate with a lower calculated risk of Down syndrome (DS). Hence, erroneously low hCG results due to fibrin clot may lead to misinterpretation. We present a 23-year-old woman with a pregnancy of 17+3 weeks. Blood was taken into the Becton-Dickinson (BD) vacutainer SST-II Advance tube (Ref: 367955). The hCG test was performed on Immulite 2000 XPi analyser (Siemens Healthcare Diagnostics Inc, Tarrytown, USA) with original reagents. The results of the same sample were found as 2566 U/L, 18,153 U/L, and 7748 U/L. Three consecutive results after removal of the small fibrin clot and recentrifugation were 18,878, 20,255, and 22,339 U/L. The risk of DS and MoM for the concentration of 2556 U/L hCG was < 1/10,000 and 0.14, respectively. For a hCG concentration of 20,255 U/L, these values were 1/5632 and 1.13, respectively. Laboratory professionals and technicians should be aware that erroneously low hCG results can be measured with the Immulite 2000 XPi due to interference from small fibrin clots. Falsely underestimated hCG values reduce the MoM values and thus the calculated risk of DS.

Interstitial Ectopic Pregnancy-Case Reports and Medical Management.

The term intramural (interstitial) ectopic pregnancy refers to a pregnancy developing outside the uterine cavity, with a gestational sac implanted into the interstitial part of the Fallopian tube, surrounded by a layer of the myometrium. The prevalence rate of interstitial pregnancy (IP) is 2-4% of all ectopic pregnancies. Surgery is the primary treatment for interstitial ectopic pregnancy; the pharmacological management of ectopic pregnancy, including IP, in asymptomatic patients includes systemic administration of methotrexate. In this report, we present two cases of this rare pregnancy type, reviewing our management technique and treatment ways presented in the literature. In our patients, the management was initially conservative and included methotrexate, administered as intravenous bolus injection, regular beta-human chorionic gonadotropins (ß-HCG) level measurements in peripheral blood, and monitoring of the patient's general condition. Due to signs of intra-abdominal bleeding in patient A and inadequate ß-HCG level reduction in patient B, both patients eventually underwent laparoscopic cornual resection. Pregnancy, implanted into the interstitial part of the Fallopian tube and surrounded by myometrial tissue with myometrial invasion of the trophoblast, poses a serious diagnostic challenge to modern gynecology due to particularly low sensitivity and specificity of symptoms, and may require both pharmacological and surgical treatment.

Efficacy of suction curettage as the first-line treatment of cesarean scar pregnancy: A retrospective study.

OBJECTIVE: There is still no consensus on a safe and efficient treatment modality for cesarean scar pregnancy (CSP), which is known to cause severe complications, such as life-threatening hemorrhage. Suction curettage (SC) has been used as the first-line treatment for CSP with controversial outcomes. In this context, the objective of this study is to analyze the efficacy of SC in the treatment of CSP. METHODS: The sample of this retrospective study consisted of 64 CSP patients treated using SC between 2012 and 2022. Patients' demographic and clinical variables, including the thickness of the myometrium at the lower uterine segment between the urinary bladder and cesarean scar, were obtained from their medical records. The study's primary outcome was determined as the success rate of SC. Accordingly, the patients were categorized into two groups: successful SC (Group 1) and unsuccessful SC (Group 2). RESULTS: The success rate of SC was determined as 78.1%. The number of previous cesarean deliveries, gestational age, baseline beta-human chorionic gonadotropin (ß-hCG) values, and endometrial thickness was significantly higher in Group 2 (p<0.05 for all), whereas the fetal cardiac activity and absence of an embryonic pole were significantly higher in Group 2 (p = 0.001 and p = 0.004, respectively). There was no significant difference between the groups in the thickness of the myometrium at the lower uterine segment (p = 0.890). The hemoglobin levels decreased significantly after SC in both Groups 1 and 2 (p<0.001 and p = 0.009, respectively). There was no significant difference between the groups in preoperative and postoperative hemoglobin values and the decrease in hemoglobin levels (p>0.05). CONCLUSION: The study findings did not indicate any significant correlation between myometrial thickness at the lower uterine segment and the efficacy of SC in CSP patients. On the other hand, the number of cesarean deliveries, gestational age, baseline ß-hCG values, endometrium thickness, fetal cardiac activity, and embryonic pole may be used to predict the outcome of SC in the treatment of CSP.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening.

INTRODUCTION: Extreme levels of either PAPP-A or free ß-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. METHODS: A total number of 8591 patients with singleton pregnancies between 11 + 0-13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free ß-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. RESULTS: Values of PAPP-A ≥ 2,0 MoM and free ß-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free ß-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free ß-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free ß-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free ß-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DISCUSSION: Pregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free ß-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free ß-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

Extreme ßHCG levels in first trimester screening are risk factors for adverse maternal and fetal outcomes.

Multiples of the normal median (MoM) of free ßHCG is a valuable parameter in evaluation of risk of adverse pregnancy outcomes. In the current retrospective study, we assessed the maternal and fetal outcomes in pregnant women having free ßHCG MoM levels < 0.2 or > 5 in their first trimester screening (FTS). Relative risk of trisomy 21 was significantly higher in patients having free ßHCG MoM > 5. On the other hand, relative risk of trisomies 13 and 18 and Turner syndrome were higher in those having free ßHCG MoM < 0.2. Other chromosomal abnormalities were nearly equally detected between those having free ßHCG MoM < 0.2 or > 5. Relative risk of hydrocephaly and hydrops fetalis was higher when free ßHCG MoM was below 0.2. On the other hand, relative risk of low birth weight was higher when free ßHCG MoM was above 5. Moreover, frequency of gestational diabetes mellitus, preeclampsia, preterm delivery and vaginal bleeding increased with levels of free ßHCG MoM. However, polyhydramnios had the opposite trend. Frequencies of premature rupture of membranes and pregnancy induced hypertension were highest among pregnant women having levels of free ßHCG MoM < 0.2. The current study indicates importance of free ßHCG MoM in identification of at-risk pregnancies in terms of both fetal and maternal outcomes. In fact, ßHCG MoM < 0.2 or > 5 can be regarded as risk factors for adverse maternal or fetal outcomes irrespective of the presence of other abnormalities in the FTS results.

Evaluation of pretreatment and early treatment changes in serum ß-hCG with methotrexate.

BACKGROUND: Serum beta-human chorionic gonadotropin (ß-hCG) is an important biomarker for the detection of ectopic pregnancies (EPs). The ß-hCG levels between days 1 and 4 after methotrexate (MTX) treatment as an indicator of the success of the MTX in EP have been the focus of research. OBJECTIVES: To determine whether the change in the ß-hCG levels at day 1 and 4 and pretreatment at 48-hour increments can predict early treatment failure of single-dose MTX in EP. MATERIAL AND METHODS: This was a retrospective study of 1120 EPs treated with a single dose of MTX. Treatment failure was defined as an obligation to proceed to surgery or the need for additional doses of MTX. RESULTS: A total 722 out of 1120 EPs had an increase in ß-hCG on day 4 after MTX treatment. The logistic regression analysis indicated that 3 dependents were significantly associated with treatment failure: 1) a pretreatment 48-hour increase in ß-hCG (odds ratio (OR): 1.249, 95% confidence interval (95% CI): 1.008-2.049, p < 0.001); 2) a change in ß-hCG between day 1 and 4 (OR: 1.384, 95% CI: 1.097-2.198, p < 0.001); and 3) a history of EP (OR: 1.208, 95% CI: 1.041- 2.011, p < 0.001). The optimal cutoff point for the prediction of treatment failure was an increase of more than 19% in the 48 h before the treatment, and an increase of more than 36% between day 1 and day 4 in ß-hCG concentrations. Patients with an increase in ß-hCG levels of less than 36% on day 4 experienced MTX treatment failure in 4.2% (n = 25), compared to 74.5% (n = 88) of the patients with an increase above 36%. CONCLUSIONS: A serum ß-hCG increase of more than 36% on day 4 after the administration of MTX alongside a more than 19% increase in ß-hCG concentration 48 h before the MTX treatment may predict the early failure of medical treatment for an EP.

Rectal ectopic pregnancy after in vitro fertilization and embryo transfer: A case report.

RATIONALE: Rectal ectopic pregnancy is an extremely rare abdominal pregnancy. This article presents a female underwent an unsuccessful in vitro fertilization which was misdiagnosed by serum beta-human chorionic gonadotropin (ß-hCG) test and transvaginal ultrasonography. Twenty days later, a ruptured rectal ectopic pregnancy was confirmed by laparoscopy then the gestational tissue removed successfully. PATIENT CONCERNS: A 32-year-old Chinese female was admitted to our hospital with complaining of symptoms, like gradual worsening of lower abdominal pain and dysuria. The abdominal ultrasonography revealed a sac-like mass in the posterior area to the uterus and a moderate amount of free fluid in the pelvic cavity. Forty days ago, she underwent a frozen embryo transfer. Twenty days ago, her serum ß-hCG level was <5 mIU/mL and neither intrauterine nor ectopic pregnancy was detected by transvaginal ultrasonography. Then the procedure was thought to have resulted in biochemical pregnancy failure. DIAGNOSIS: The primary rectal ectopic pregnancy. INTERVENTIONS: The mass was removed laparoscopic surgery. OUTCOMES: The patient recovered well. LESSONS: When the history of in vitro fertilization combined with an inappropriate rise of serum ß-hCG and no visible evidence of an intra-uterine pregnancy, physicians should consider the possibility of abdominal pregnancy. Early diagnosis of abdominal pregnancy can effectively save the life of the pregnant woman.

Diagnostic efficacy of aneuploidy markers correlated with early onset preeclampsia.

Low-dose aspirin administration before 16 weeks of gestation can prevent preeclampsia (PE) more effectively. In order to determine if aspirin should be administered, this study aimed to investigate the predictive value of pregnancy-associated plasma protein A (PAPP-A) and aneuploidy markers for the onset period of PE. 1053 singleton pregnant women were included in the study, and serum PAPPA-A and aneuploidy markers were analyzed between 3 group (normotensive, late-onset PE, and early-onset PE). The utility of these markers for predicting early-onset preeclampsia (EOPE) was compared using each marker and their combination. Alpha-fetoprotein (AFP)/PAPP-A > 6.89 and human chorionic gonadotropin (hCG)/PAPP-A > 7.94 were associated with EOPE with a positive likelihood ratio (LR) (6.52, 95% confidence interval [CI] 4.9-7.1), and (5.77, 95% CI 3.9-6.4). The combination of markers could predict EOPE more accurately compared to the single markers. AFP/PAPP-A > 6.89 and hCG/PAPP-A > 7.94had a predictive ability for EOPE, and these cutoff values can help determine the use of aspirin at an earlier gestational age (GA).

First-Trimester Biochemical Serum Markers in Female Kidney Transplant Recipients-The Impact of Graft Function.

Data on serum biochemistry markers as a component of the first-trimester screening test in pregnant kidney graft recipients are limited. In the absence of a separate validated algorithm, biochemical testing is commonly used in the first-trimester screening in kidney transplant recipients. Therefore, the study aimed to analyze first-trimester serum biochemical markers and the first trimester combined screening results in pregnant kidney graft recipients. A retrospective study was carried out in pregnant women who underwent the first-trimester combined screening test performed per the Fetal Medicine Foundation (FMF) protocol in 2009−2020. The study group included 27 pregnancies in kidney graft transplant recipients, and the control group was 110 patients with normal kidney function, matched according to age, body mass index (BMI), and gestational age. The biochemical serum markers (free beta-human chorionic gonadotropin [beta-hCG] and pregnancy-associated plasma protein A [PAPP-A]) were evaluated using the FMF-approved Roche Elecsys® assay and exhibited as multiples of the median (MoM) values. Data on first-trimester screening test results, perinatal outcomes, and graft function (assessed using serum creatinine concentrations) were analyzed. The analysis of first-trimester screening parameters revealed no difference in nuchal translucency (NT) measurements and uterine artery flow. However, free beta-hCG MoM and PAPP-A values were higher in posttransplant pregnancies than in controls: 3.47 ± 2.08 vs. 1.38 ± 0.85 (p = 0.035) and 1.46 ± 0.81 vs. 0.98 ± 0.57 (p = 0.007), respectively. The false positive rate of trisomy 21 (T21) screening in graft recipients was 25.9% vs. 3% in the controls. The free ß-hCG MoM values positively correlated with serum creatinine levels before (r = 0.653; p < 0.001), during (r = 0.619; p = 0.001), and after pregnancy (r = 0.697; p < 0.001). There was a statistically significant negative correlation for PAPP-A MoM values for postpartum serum creatinine concentration (r = −0.424, p = 0.035). Our results show significantly higher serum concentrations of free beta-hCG and PAPP-A in posttransplant pregnancies than in healthy controls, confirmed when exhibited as MoM values and their association with graft function was assessed by serum creatinine concentration. Taking those changes into account would reduce the high number of false positive test results in this group. The validated first-trimester screening algorithm that considers altered kidney function in pregnant kidney graft recipients remains to be developed.

Ruptured ovarian ectopic pregnancy presenting with an acute abdomen.

An ectopic pregnancy occurs in 2% of all pregnancies. A primary ovarian ectopic (OP) is a rare entity and occurs in <2% of all ectopic gestations. It may present in those individuals who take ovulatory drugs, use an intrauterine device or have undergone in vitro fertilisation or embryo transfer. Multiparity and a younger age are other recognised risk factors. Diagnosing an OP pregnancy remains a challenge and it may be misdiagnosed as a bleeding luteal cyst, a haemorrhagic ovarian cyst or a tubal pregnancy by ultrasound scan. The diagnosis is often only established at laparoscopy following histopathological examination. A ruptured OP is a potentially life-threatening condition due to its potential for haemorrhage and hemodynamic collapse. Hence, early diagnosis is crucial to prevent serious morbidity and mortality. The authors present the case of a multiparous woman in her late 30s presenting with a seizure and lower abdominal pain at 6 weeks gestation. Her beta human chorionic gonadotropin was >9000 Miu/mL. A transvaginal ultrasound scan showed no evidence of an intrauterine pregnancy. There was free fluid in the pelvis. She was hemodynamically stable. She underwent a diagnostic laparoscopy, which showed hemoperitoneum and a ruptured left OP pregnancy. She underwent a left oophorectomy. Histology confirmed chorionic villi within the ovarian stroma. This case demonstrates the challenges in preoperative diagnosis of a ruptured OP pregnancy and acts as a cautionary reminder that individuals can present with hemodynamic stability. Rarely, as in this case, an OP pregnancy can occur without the presence of risk factors. Despite its rarity, a ruptured OP pregnancy should be considered in the differential diagnosis of women of reproductive age presenting to the emergency department with acute abdominal pain and a positive pregnancy test.

Identification of noninvasive diagnostic biomarkers for ectopic pregnancy using data-independent acquisition (DIA)proteomics: a pilot study.

At present, the diagnosis of ectopic pregnancy mainly depends on transvaginal ultrasound and ß-hCG. However, these methods may delay diagnosis and treatment time. Therefore, we aimed to screen for serological molecular markers for the early diagnosis of ectopic pregnancy (EP).Using data-independent acquisition (DIA)proteomics, the differential proteins in serum were selected between the intrauterine pregnancy (IP) and EP groups. Then, the expression levels of these differential proteins were measured by enzyme-linked immunosorbent assay. The diagnostic value of the serum biomarkers was evaluated by receiver operating characteristic curve analysis.GSTO1, ECM-1 and ß-hCG showed significant differences between the EP and IP groups (P < 0.05). The combination of GSTO1/ECM-1/ß-hCG had an area under the curve of 0.93 (95% CI 0.88-0.99), a sensitivity of 88.89% (95% CI 73.94-96.89) and a specificity of 86.11% (95% CI 70.50-95.33) with a likelihood ratio of 6.40.The combination of GSTO1/ECM-1/ß-hCG may be developed into a possible approach for the early diagnosis of EP.

Independent value of serum ß-human chorionic gonadotropin in predicting early pregnancy loss risks in IVF/ICSI cycles.

Background: Early pregnancy loss (EPL) is the most prevalent complication, particularly in couples undergoing assisted reproductive technology treatment. The present study aimed to determine whether the serum ß-human chorionic gonadotropin (ß-hCG) level after 14 days of embryo transfer, either alone or in conjunction with other parameters in IVF/ICSI cycles, could be used to predict subsequent EPL. Methods: This was a retrospective cohort study of all couples who received clinical pregnancy and underwent fresh IVF/ICSI cycles at a single large reproductive medical center between January 2013 and June 2020. The research involved a total of 6600 cycles. For risk variables, we conducted the least absolute shrinkage and selection operator (LASSO) analysis, and for risk scoring, we used logistic regression coefficients. To analyze relevant risk factors for EPL, univariate and multivariate logistic regression analyses were employed. Areas under the curve (AUC) were determined and compared between ß-hCG and other factors using receiver operating characteristic (ROC) curves. Results: ß-hCG level was considerably lower in women who had EPL than in those who were ongoing pregnancy (564.03 ± 838.16 vs 1139.04 ± 1048.72 IU/L, p< 0.001). Univariable and multivariable logistic regression revealed that ß-hCG levels were significantly correlated with the probability of EPL, independent of other risk factors. More importantly, the ß-hCG level could independently predict the occurrence of EPL and was comparable to the model that combined other risk factors. The optimal serum ß-hCG cut-off value for predicting EPL was 542.45 IU/L. Conclusions: Our results suggest that the serum ß-hCG level has a strong independent predictive value for EPL occurrence in fresh IVF/ICSI cycles.

Prospective multicentre Italian pregnancy cohort study (SIMPLE) on the associations of maternal first trimester SIMPLE nutritional score with early placental function markers and pregnancy outcomes.

INTRODUCTION: Currently, the adherence to nutritional guidelines is low, with alarming rates of obesity worldwide and micronutrient deficiencies documented even in industrialised countries. As a consequence, nutritional screening and counselling represent a critical subject in early pregnancy, aiming to improve pregnancy outcomes and population health. METHODS AND ANALYSIS: In this setting, the development of a simple and reproducible nutritional checklist is of utmost importance. The Simple Study is a longitudinal prospective multicentre study aiming to identify the associations between maternal nutritional habits in the first trimester, early markers of placental function and pregnancy outcomes on a large population of singleton pregnancies in Italy.Ongoing healthy singleton pregnancies will be enrolled at the ultrasound scan of the first trimester combined screening test (11+0-13+6 gestational weeks). A nutritional score measuring the adherence to a healthy diet and nutritional deficiencies will be collected at recruitment. Fetal (crown-rump length, nuchal translucency (NT), biparietal diameter, femur length) and utero placental (placental volume, uterine arteries Doppler velocimetry) ultrasound data and biochemical placental markers (pregnancy-associated plasma protein A, free ß-human chorionic gonadotropin) will be collected. Second and third trimester ultrasound records and birth outcomes will be recorded from medical registers. This study will set the stage for introducing a reproducible, time-saving and low-cost nutritional screening in pregnancy. The nutritional score will allow the implementation of specific corrective measures with potential large impact on placentation and pregnancy outcomes. ETHICAL AND DISSEMINATION: Ethical approval for this study was obtained from the Milano Area 1 Ethics Committee (No 46091, 7 November 2018) prior to the commencement of the research.The dissemination plan includes the presentation of abstracts and findings at national and international scientific meetings.