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Complete hydatidiform mole (HM) is a gestational trophoblastic disease resulting in hyperproliferation of trophoblast cells and absence of embryo development. Mutations in the maternal-effect gene NLRP7 are the major cause of familial recurrent complete HM. Here, we established an in vitro model of HM using patient-specific induced pluripotent stem cells (iPSCs) derived trophoblasts harboring NLRP7 mutations. Using whole transcriptome profiling during trophoblast differentiation, we showed that impaired NLRP7 expression results in precocious downregulation of pluripotency factors, activation of trophoblast lineage markers, and promotes maturation of differentiated extraembryonic cell types such as syncytiotrophoblasts. Interestingly, we found that these phenotypes are dependent on BMP4 signaling and BMP pathway inhibition corrected the excessive trophoblast differentiation of patient-derived iPSCs. Our human iPSC model of a genetic placental disease recapitulates aspects of trophoblast biology, highlights the broad utility of iPSC-derived trophoblasts for modeling human placental diseases and identifies NLRP7 as an essential modulator of key developmental cell fate regulators.

In humans, parthenogenesis and androgenesis occur naturally in mature cystic ovarian teratomas and androgenetic complete hydatidiform moles (CHM), respectively. Our previous study has reported human parthenogenetic induced pluripotent stem cells from ovarian teratoma-derived fibroblasts and screening of imprinted genes using genome-wide DNA methylation analysis. However, due to the lack of the counterparts of uniparental cells, identification of new imprinted differentially methylated regions has been limited. CHM are inherited from only the paternal genome. In this study, we generated human androgenetic induced pluripotent stem cells (AgHiPSCs) from primary androgenetic fibroblasts derived from CHM. To investigate the pluripotency state of AgHiPSCs, we analyzed their cellular and molecular characteristics. We tested the DNA methylation status of imprinted genes using bisulfite sequencing and demonstrated the androgenetic identity of AgHiPSCs. AgHiPSCs might be an attractive alternative source of human androgenetic embryonic stem cells. Furthermore, AgHiPSCs can be used in regenerative medicine, for analysis of genomic imprinting, to study imprinting-related development, and for disease modeling in humans.

Background: Gestational trophoblastic diseases (GTDs) are treatable rare tumors with wide distribution. The estimated incidence of GTDs varies dramatically between different regions globally. In early pregnancy, there may be high human chorionic gonadotropin (HCG) concentrations, normal or slightly increased free T4 (fT4) and subnormal thyroid-stimulating hormone (TSH), causing hyperthyroidism ranging from subclinical to severe. Beta-HCG causes thyrotoxicosis through thyroid stimulation in patients with trophoblastic tumors., Objective: To assess thyroid function among patients diagnosed with complete or partial hydatidiform mole, within the GTD spectrum., Design and Setting: Cross-sectional study based on patients' medical records at Van University Hospital, Van, Turkey., Methods: 50 patients monitored due to diagnoses of hydatidiform mole were included and were examined regarding thyroid function. Thyroid gland size and volume were measured using thyroid ultrasonography. Beta-HCG, TSH, fT4, free T3 (fT3), total T4 (TT4), total T3 (TT3), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and thyroglobulin levels were measured., Results: Among these patients, 15 (30%) were diagnosed with complete hydatidiform mole and 35 (70%) with partial hydatidiform mole, according to pathology results. Those with complete hydatidiform mole were older (P = 0.003), with higher number of pregnancies (P = 0.032), lower TSH level (P = 0.011) and higher fT4 and TT4 levels (P = 0.04; P = 0.028), compared with partial hydatidiform mole patients., Conclusion: In hydatidiform mole patients, thyroid disease severity increases with age, parity, beta-HCG level and mole size. However, prospective multicenter studies on this topic are needed, with larger numbers of patients and closer monitoring.

Introduction: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data., Aim: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction., Methods: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles., Results: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions., Conclusion: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.

Competing Interests: Author: none, (Georg Thieme Verlag KG Stuttgart · New York.)

Recurrent hydatidiform moles (RHM) are aberrant human pregnancies characterized by absence of, or abnormal, embryonic development, hydropic degeneration of chorionic villi, and hyperproliferation of the trophoblast. Biallelic mutations in two maternal-effect genes, NLRP7 and KHDC3L, underlie the causation of RHM in 60% of patients. We performed exome sequencing on a patient with six pregnancy losses, two miscarriages and four HM, and found no variants that affect the functions of the known genes. We found biallelic missense variants that affect conserved amino acids in PADI6 and segregate with the disease phenotype in the family. PADI6 is another maternal-effect gene and a member of the subcortical maternal complex that has been shown to have recessive variants that affect the gene function in four unrelated women with infertility who also experienced early embryonic arrest during preimplantation development after IVF. We demonstrated that PADI6 co-localizes with NLRP7 in human oocytes and preimplantation embryos and reviewed the morphology and genotypes of four products of conception from our patient. Our data expand the involvement of PADI6 to other forms of reproductive loss and highlight the commonality between infertility, miscarriages, and molar pregnancies, in some cases.

Objectives:: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia., Methods:: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon's test, logistic regression, and ROC analysis., Results:: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia., Conclusions:: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.

The paper describes a case of twin pregnancy with complete hydatidiform mole (CHM). According to the data available in the literature, the concurrence of CHM with a normal placenta and a viable fetus occurs in 1 per 20,000-100,000 pregnancies, requires a differential diagnosis with partial hydatidiform mole and placental mesenchymal dysplasia, and is characterized by a high rate of complications. In this concurrence, the frequency of persistent trophoblastic disease is as high as 50%. In this case, the pregnancy ended in a spontaneous abortion at 16-17 weeks of pregnancy. A morphological examination determined the fetus without congenital malformations with normal placental weight and structure and the adjacent intact placental tissue with the macro- and microscopic signs of CHM. The diagnosis was confirmed by the lack of р57 expression in the villous trophoblast and stroma in the tissue of the hydatidiform mole. The patient was diagnosed with persistent trophoblastic disease at 2 months after the abortion.

Background & Objectives: There is considerable inter-observer variability in the diagnosis of molar pregnancies by histomorphological examination of products of conception (POC). The p57KIP2 gene is paternally imprinted and expressed from the maternal allele. On immunohistochemistry (IHC) with p57, complete mole (CM) shows absent staining whereas hydropic abortus (HA) and partial mole (PM) show positive staining. This study was undertaken to evaluate the role of p57 IHC along with histomorphology in differentiating between CM, PM and non-molar or HA., Methods: This was a cross-sectional study over a period of three and a half years on archival material. Detailed histomorphological review along with p57 IHC was carried out in 28 diagnosed cases (23 CM, 4 PM and 1 molar pregnancy not categorized) and 25 controls of four normal placentas and 21 POC (8 non-hydropic and 13 HA)., Results: In 14.8 per cent (4/27) cases, there was discordance in accurate subtyping of molar pregnancy. One case of CM showed inconsistent IHC pattern. In 15.4 per cent (2/13) HA, molar pregnancy was final diagnosis. After final review, there were 25 CM, five PM, 22 non-molar controls including 10 HA and one not assigned (PM/HA). IHC with p57 was negative in 96 per cent CM and positive in 100 and 95 per cent PM and non-molar controls, respectively., Interpretation & Conclusions: This study showed that negative p57KIP2 immunostaining reliably identified CM and could be used in association with the histological findings to distinguish CM from its mimics.

Ectopic molar pregnancy is a rare occurrence and consequently not often considered as a diagnostic possibility. We report two cases of molar hydatidiform tubal pregnancy. Diagnosis of ectopic pregnancy was confirmed on clinical biological and sonographic investigations. Diagnosis of molar pregnancy was done on histopathology. The clinical course was favorable for both patients. Although rare, molar changes can occur at any site of an ectopic pregnancy. Clinical diagnosis of a molar pregnancy is difficult but histopathology is the gold standard for diagnosis., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Aim: To assess the use of magnetic resonance imaging (MRI) for prenatal differentiation between complete hydatidiform mole with a twin live fetus (CHMTF) and placental mesenchymal dysplasia (PMD)., Methods: Three CHMTF cases and three PMD cases, from two institutions over a 6-year period, were retrospectively included in this study. Clinical findings including age, pregnancy history, serum hCG level, ultrasonography findings, complications of the mother, outcome of the fetus, and results of chromosomal study of fetus, amniotic fluid and lesion, if possible, were noted. MRI findings were evaluated by two radiologists with respect to the location of the disease (intra- or extra-fetal sac), the presence of multicystic component, and presence of intra- or extra-lesional hemorrhage., Results: In all six cases, the diseases were recognized as multicystic lesions by ultrasonography and MRI. In two of three CHMTF cases, patients continued with the pregnancy, which resulted in spontaneous abortion. In one case of CHMTF, the patient underwent artificial abortion, after which the mole progressed into an invasive mole with lung metastases. All three PMD patients had live births, and two of the three babies had fetal growth restriction. By MRI, CHMTF was located within an extra-fetal sac accompanied by intra- and/or extra-lesional hemorrhage, while PMD was located within the placenta in the fetal sac without hemorrhage., Conclusion: MRI could provide important information about the prenatal differential diagnosis of CHMTF and PMD, based on the pathophysiology and characteristics of the diseases., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

A 23-year-old woman, gravida 1, para 1, was transferred to our hospital with acute lower abdominal pain and vital signs consistent with shock. Her urine concentration of human chorionic gonadotrophin was 8000 mIU/mL. Transvaginal ultrasound revealed an echo-free space with mosaic echo pattern in the right adnexal area and no gestational sac in the uterus. With a preoperative diagnosis of ruptured ectopic pregnancy, emergency laparotomy was performed. The rectouterine pouch was filled with many clots containing small amounts of villous tissue. After removal of the conceptus, which was infiltrating into the peritoneum of the Pouch of Douglas, bleeding was controlled by Argon laser. Histological examination of the conceptus by immunohistochemical staining with p57(kip2) showed features of complete hydatidiform mole. This case demonstrates that the peritoneum in the Pouch of Douglas is a possible site of ectopic complete hydatidiform mole occurrence and that immunohistochemical stain is useful to confirm the diagnosis of ectopic complete hydatidiform mole., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Introduction: The effect of a hyperthyroid or euthyroid state on liver function tests in patients with hydatidiform moles (HM) is not known. The aim of this study was to determine the effect of hyperthyroidism on liver transaminases in HM., Patients and Methods: We retrospectively reviewed aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in 80 patients with HM (23 complete moles and 57 partial moles)., Results: Of the 80 HM patients, 52 (65%) were euthyroid and 28 (35%) were hyperthyroid. The number of gravida and the levels of serum β-human chorionic gonadotropin (β-HCG), AST, and ALT were significantly higher in the hyperthyroid state than in the euthyroid state (p = 0.033, p = 0.001, p = 0.001 and p = 0.001; respectively). Number of gravida, serum TSH and total T4 were significantly higher in complete HM than partial HM (p < 0.05, p < 0.001, p < 0.05; respectively)., Conclusions: Our results demonstrated that HM-related β-HCG may activate thyroid cells via TSH-related signalling, resulting in the release of high levels of FT4, FT3, TT3 and TT4, and a subsequent decrease in TSH.

Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: The loss of primordial follicles from gonadal damage caused by chemotherapy results in decreased ovarian reserve. To assess the impact of chemotherapy for patients with gestational trophoblastic neoplasia (GTN) on the ovarian reserve, we evaluated the post-chemotherapy serum anti-Müllerian hormone (AMH) levels., Study Design: In 22 patients with GTN receiving chemotherapy, serum AMH levels were measured after the administration of chemotherapy and compared with serum AMH levels measured in patients with hydatidiform mole who did not receive chemotherapy, as a control. We also analyzed differences in the serum AMH levels following the administration of different anti-cancer agents., Results: The serum AMH levels measured in the GTN group after chemotherapy was administered (median 1.18, range 0.32-3.94 ng/mL) significantly decreased in comparison to those measured in the control group (median 4.22, range 0.77-6.53 ng/mL, P=0.002). Serum AMH levels were significantly lower in the patients who had received a regimen including etoposide than in the patients who had not received treatment with etoposide (0.71 vs. 1.30 ng/mL, P=0.027)., Conclusion: Our results suggest that chemotherapy administered to treat GTN does indeed affect the ovarian reserve, especially in patients who receive a medication regimen that includes etoposide. Measuring their serum AMH levels might therefore be helpful for counseling GTN patients regarding their ovarian reserve., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Recent studies have demonstrated the value of ancillary techniques, including p57 immunohistochemistry and short tandem repeat genotyping, for distinguishing hydatidiform moles (HM) from nonmolar specimens and for subtyping HMs as complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). With rare exceptions, CHMs are p57-negative and androgenetic diploid; partial hydatidiform moles are p57-positive and diandric triploid; and nonmolar specimens are p57-positive and biparental diploid. Androgenetic/biparental mosaic/chimeric conceptions can have morphologic features that overlap with HMs but are genetically distinct. This study characterizes 11 androgenetic/biparental mosaic/chimeric conceptions identified in a series of 473 products of conception specimens subjected to p57 immunohistochemistry and short tandem repeat genotyping. Fluorescence in situ hybridization was performed on 10 to assess ploidy. All cases were characterized by hydropically enlarged, variably sized and shaped villi. In 5 cases, the villi lacked trophoblastic hyperplasia, whereas in 6 there was a focal to extensive villous component with trophoblastic hyperplasia and features of CHM. The villi lacking trophoblastic hyperplasia were characterized by discordant p57 expression within individual villi (p57-positive cytotrophoblast and p57-negative stromal cells), whereas the villous components having trophoblastic hyperplasia were uniformly p57-negative in both cell types. Short tandem repeat genotyping of at least 2 villous areas in each case demonstrated an excess of paternal alleles in all regions, with variable paternal:maternal allele ratios (usually >2:1); pure androgenetic diploidy was identified in those cases with a sufficiently sized villous component having trophoblastic hyperplasia and features of CHM. Fluorescence in situ hybridization demonstrated uniform diploidy in 7 cases, including 4 of 5 tested cases with trophoblastic hyperplasia and 3 of 5 cases without trophoblastic hyperplasia. Two cases without trophoblastic hyperplasia had uniformly diploid villous stromal cells but 1 had triploid and 1 had tetraploid cytotrophoblast; 1 case with trophoblastic hyperplasia had uniformly diploid villous stromal cells but a mixture of diploid, triploid, and tetraploid cytotrophoblast. In 3 cases with a CHM component, persistent gestational trophoblastic disease developed. These results indicate that androgenetic/biparental mosaic/chimeric conceptions are most often an admixture of androgenetic diploid (p57-negative) and biparental diploid (p57-positive) cell lines but some have localized hyperdiploid components. Recognition of their distinctive p57 expression patterns and genotyping results can prevent misclassification as typical CHMs, PHMs, or nonmolar specimens. The presence of androgenetic cell lines, particularly in those with a purely androgenetic CHM component, warrants follow-up because of some risk of persistent gestational trophoblastic disease.

Background: Complete hydatiform mole and coexistent viable fetus is very rare. The use of a cervical cerclage for cervical indications in the presence of this condition has never been reported. Although the diagnosis was made postnatal, the objective is to present a case with good neonatal outcome., Case Presentation: A patient presented with vaginal spotting around 23 weeks. She has a history of four preterm deliveries. Her cervix was dilated and a cerclage was placed. She presented again with PPROM around 25 weeks. She went into spontaneous preterm labor and delivered a viable fetus that is a healthy girl today. Eventually the pathology of the placenta showed a complete hydatidiform mole., Conclusion: It is necessary to inform patients about the potential risks and poor outcomes of this condition. For those who desire all potential interventions, cerclage placement could be considered.

Objective: To evaluate serum human chorionic gonadotropin (hCG) ratio, progesterone and inhibin A as single parameters and in combination for the prediction of spontaneous resolution of pregnancies of unknown location (PUL)., Study Design: Prospective observational study of 105 consecutive patients with a diagnosis of PUL. Serum levels of hCG, progesterone and inhibin A were determined at the first visit and after 2 days. Patients were followed clinically until a final diagnosis of spontaneously resolving PUL, viable or non-viable intrauterine pregnancy, or ectopic pregnancy with need of laparoscopic intervention had been reached. Different combinations of hCG ratio (hCG at 48 h/hCG at 0 h), s-progesterone and s-inhibin A were investigated to find the best predictor for successful expectant management., Results: The final pregnancy outcomes were: 52 spontaneously resolving PUL (49.5%), 37 viable intrauterine pregnancies (35.2%), 8 non-viable intrauterine pregnancies (7.6%), 7 ectopic pregnancies (6.7%), and one molar pregnancy (1.0%). An hCG ratio<0.80 predicted spontaneously resolving PUL with positive and negative predictive values (PPV and NPV), sensitivity, and specificity of 0.98, 0.78, 0.72, and 0.99, respectively. In patients with hCG ratio ≥ 0.80, a combination of s-progesterone < 20 nmol/l and s-inhibin A < 30 pg/ml predicted spontaneously resolving PUL with PPV, NPV, sensitivity and specificity of 0.92, 0.96, 0.85, and 0.98 respectively., Conclusion: Our results suggest that patients with PUL and hCG ratio < 0.80 display a high probability of spontaneously resolving PUL with minimum need of follow-up. In cases of hCG ratio ≥ 0.80, a combination of s-progesterone < 20 nmol/l and s-inhibin A < 30 pg/ml, may be a reliable predictor of spontaneously resolving PUL. The safety of this approach should be tested in large prospective studies., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

This is an analysis of the incidence of molar pregnancies and those of complete and partial molar pregnancies across the reproductive age range for BP Koirala Institute of Health Sciences (BPKIHS) in the period 2010-2011. Patients with molar pregnancies registered with BPKIHS from January 2008 to January 2010 were identified. The overall number of molar pregnancies registered was compared to the number of maternities (live births and still births) and total viable conceptions for this year. A retrospective study of 64 cases of molar pregnancies recorded at BPKIHS during the two year time was done. Medical records were reviewed. Incidence, clinical presentation and methods of diagnosis were studied. During the study period, there were 37 complete moles, 23 partial moles, 1 persistent gestational trophoblastic tumor, 1 choriocarcinoma, and 2 invasive moles. The incidence of molar pregnancy was 3.94 per 1000 deliveries. Median distribution was at 22 years of age, and majority (67%) presented during early second trimester. Twenty one (32.8%) women were of blood group A positive and ten (15.6%) presented with severe form of anemia. This study provides detailed data regarding the incidence of partial and complete molar pregnancies with increasing maternal age. It confirms the relation of molar pregnancy with age, and blood group. Complete mole had the highest incidence, affecting mostly younger age group, and usually in the first half of their pregnancy.

Objective: To evaluate (i) insulin resistance and C-reactive protein (CRP) levels in women with complete hydatidiform mole (CHM) and (ii) whether there were any correlations between these parameters and CHM., Methods: Thirty-two women with CHM and 30 healthy pregnant women were enrolled in the study. Fasting serum glucose and insulin levels, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG) and C-reactive protein (CRP) were measured. Insulin resistance was calculated by the homeostasis model assessment ratio (HOMA-IR)., Results: Fasting glucose, insulin, HOMA-IR, CRP, and TG levels were higher, and HDL was lower among patients with CHM compared with healthy pregnant group (p < 0.05 for all). There were positive associations between CHM status and glucose, insulin, HOMA-IR, CRP, TG levels and had a negative correlation with HDL (p < 0.05 for all). The receiver operating characteristic curve (ROC) analysis value for HOMA-IR in CHM was 0.96 (95% confidence interval (CI) = 0.92-1.00), sensitivity = 94%, and specificity = 87%. The area under ROC curve value for CRP was 0.72 (95% confidence interval (CI) = 0.58-0.84), sensitivity = 82%, and specificity = 60% in CHM., Conclusions: Insulin resistance and CRP were found to be higher among patients with CHM. These parameters were also closely associated with CHM. Further studies are needed to investigate the nature of this link in this group.

We report a 28-year-old woman presenting with a complete hyaditiform mole localized to the cervix. She had undergone curettage of missed abortion two months previously and the aborted material showed normal placental tissue on histopathologic examination. Two months after curettage she presented with sudden severe vaginal bleeding. Clinical examination revealed a lesion of the epithelial outer surface of the cervix. Due to the bleeding, immediate surgical intervention was necessary. Histological examination revealed a complete hydatidiform mole. Currently, only three cases of this exceedingly rare diagnosis have been published: two reported a partial mole and one a complete hydatidiform mole. In our case, we hypothesize that the pathogenesis took place in two steps. Initially the curettage of the missed abortion damaged the endometrial lining. During a new rapid re-fertilization after the missed abortion, a hydatidiform molar pregnancy developed. Normally this abnormal trophoblast tissue would adhere to the endometrium but in this case we assume that intrauterine implantation was not possible because of endometrial damage at the prior curettage, allowing the abnormal trophoblast tissue to pass the endocervix and emerge into the vaginal vault. Presumably, during the curettage an epithelial defect was produced on the outer surface of the cervix, due to clamping the cervix during dilatation. We speculate that this weak spot on the epithelial surface was responsible for the adherence to the cervix and subsequent bleeding was caused by injury of maternal blood vessels. We propose that careful holding of the cervix with atraumatic clamps during curettage is important to avoid subsequent complications., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Occurrence of gestational trophoblastic neoplasia (GTN) and adnexal torsion is rare in postmenopause. We report a 58-year-old postmenopausal woman with adnexal torsion caused by hydatidiform mole. The patient was admitted to our clinic complaining of acute abdominal pain, nausea and vomiting lasting one day. Ultrasonography showed an enlarged uterus including hypo/hyperechogenous cystic areas in the endometrial cavity and bilateral adnexal masses. β-HCG level was investigated and determined as 157.000 IU/l, because of the suspicion of GTN in ultrasonography. Doppler sonography revealed enlarged left adnexa with absence of vascular flow. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. β-HCG decreased to normal ranges in the fourth postoperative week. The resected uterus contained an endometrial, cystic, grapelike tumor. The ovaries were enlarged bilaterally with necrotic appearance. Histopathology revealed complete hydatidiform mole and theca lutein cysts. To our knowledge, the present case is the first hydatidiform mole associated with bilateral adnexal torsion caused by theca lutein cysts in postmenopausal period., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Subsequent pregnancy outcomes following complete hydatidiform moles (CHM) are usually favorable and the risk of a second CHM less than 2%. However, a small number of women have a rare autosomal recessive condition that predisposes them to CHM. Unlike typical CHM, that are androgenetic (AnCHM), the CHM in these women are diploid and biparental (BiCHM) with a contribution from each parent to the nuclear genome. To date most women with recurrent CHM have been found to have BiCHM and to have a wide variety of mutations in the causative gene, NLRP7. Our objectives were to genotype the molar tissue and identify the NLRP7 mutations in two unrelated Turkish women with recurrent CHM. Fluorescent microsatellite genotyping of molar tissue and screening of patient DNA for NLRP7 mutations was carried out in two women with five and four CHM respectively. The first case was confirmed to have BiCHM. In addition the patient was found to have a novel homozygous mutation in exon 8 of NLRP7. All CHM examined in the second case were AnCHM and no NLRP7 mutations were identified in DNA from the patient. This report describes a further individual with BiCHM and a novel mutation in NLRP7. A second patient with similar clinical history had no mutations in NLRP7 and is the first report of a patient with four CHM where the CHM are androgenetic. This study highlights the heterogeneity of recurrent CHM and the need to investigate women with recurrent molar pregnancies for appropriate clinical management., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Clinical and experimental evidence indicates that angiogenic imbalances may participate in the mechanisms of disease of several pregnancy complications, some of which may be life threatening. This article reviews current evidence in support of this view and the possibility that the fetus may play a central role in these imbalances; it also reviews recent experimental observations that modulation of angiogenic imbalances during pregnancy may have prophylactic and/or therapeutic value., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: Molar pregnancy is associated with very early-onset preeclampsia. Since excessive circulating antiangiogenic factors may play a pathogenic role in preeclampsia, we hypothesized that molar placentas produce more antiangiogenic proteins than normal placentas., Study Design: This retrospective case-control study used a semiquantitative immunohistochemical technique to compare histologic sections of molar placentas to normal controls. Tissue slides were treated with 2 antisera: one recognized the antiangiogenic markers fms-like tyrosine kinase receptor 1 (Flt1) and its soluble form (sFlt1), while the other recognized vascular endothelial marker CD31. Stain intensity was graded from 1+ (strong focal staining) to 4+ (91-100% staining)., Results: Molar placentas (n = 19) showed significantly more staining than controls (n = 16) for Flt/sFlt1 (P < .0001)., Conclusion: There was a significant difference in Flt1/sFlt1 immunostaining intensity when molar placentas were compared to controls. This supports a hypothesis that the phenotype of preeclampsia in molar pregnancy may result from trophoblasts overproducing at least 1 antiangiogenic protein., (Copyright 2010 Mosby, Inc. All rights reserved.)

Study Design: A case of lumbar metastasis of a choriocarcinoma is presented., Objective: To present and review a rare case of metastatic choriocarcinoma in the lumbar spine., Summary of Background Data: Choriocarcinoma is a highly anaplastic malignancy derived from trophoblastic cells characterized by the secretion of human chorionic gonadotropin (hCG) and early hematogenous metastasis. However, metastatic choriocarcinoma in the spine is extremely rare. Although 2 cases of metastasis in lumbar and/or sacral vertebra have been reported, the efficacy of surgical treatment for the spinal metastasis of choriocarcinoma is not yet known., Methods: The clinical course, radiologic features, pathology, and outcome of the treatment of metastatic choriocarcinoma of the lumbar spine is reported., Results: A 38-year-old female patient with abnormal uterine bleeding 6 weeks after a normal-term delivery showed high serum levels of hCG. A whole body image analysis revealed a lesion in the L2 vertebra. After computed tomography-guided needle biopsy, a clinical and pathologic diagnosis of lumbar metastasis of choriocarcinoma was made. Surgical resection of the localized L2 vertebra lesion was performed by total en bloc spondylectomy after a poor response to initial chemotherapy with methotrexate. Postsurgically, the serum level of hCG explosively increased and local recurrences around the original L2 vertebra and epidural metastasis abruptly developed. Lung metastases also occurred concurrently and progressed and the patient eventually died to the disease., Conclusion: We have reported a rare case of lumbar metastasis of choriocarcinoma after a normal-term pregnancy. This is the first report of lumbar metastasis of choriocarcinoma treated by spinal surgery. Because surgical resection of a lumbar metastasis of choriocarcinoma involves a substantial risk of profuse hemorrhage, local recurrence and the spread of metastasis, multiagent chemotherapy in combination with radiotherapy should be preformed before surgical resection.

Objective: To investigate the clinical characteristics, management and outcome of patients with lung metastasis of invasive mole (IM) before evacuation of hydatidiform mole (HM)., Methods: Clinical data of patients with hydatidiform mole (HM) and lung metastasis of IM who were diagnosed and treated at Peking Union Medical College Hospital from Jan 2004 to Jan 2006 were analyzed retrospectively. Firstly, clinical characteristics of patients with lung metastasis of IM before evacuation of HM (positive group) were compared with that of patients without lung metastasis before evacuation of HM (negative group); secondly, management and outcome of patients with lung metastasis of IM before evacuation of HM were compared with that of patients as lung metastasis of IM diagnosed in postevacuation follow-up of HM (control group)., Results: A total of 37 cases with HM underwent CT scan of the chest before evacuation, 11 cases of which were diagnosed as lung metastasis, accounting for 30%. Compared with negative group, significant increases in positive group were found in gestational age of week [(15.0 +/- 4.0) versus (10.0 +/- 2.5) weeks, P = 0.026], and proportion of complete HM (91% versus 50%, P = 0.027). Between positive group and negative group, no significant differences were found in age, uterine size greater than expected for gestational age, large theca lutein cyst and pre-evacuation serum human chorionic gonadotropin-beta subunit (beta-hCG) level (P > 0.05). Compared with control group, significant decrease in positive group was found in the interval from first evacuation of HM to resolution of serum beta-hCG level, (83 +/- 18) days versus (126 +/- 31) days (P < 0.01). Also, no statistically significant differences between positive group and control group were noted in the complete resolution rate achieved, the average courses of resolution of serum beta-hCG level and disappearance or marked absorption of lung metastasis needed, and the total chemotherapy courses (P > 0.05)., Conclusions: Once HM is diagnosed, evacuation should be performed as soon as possible, the later the evacuation begins, the higher the risks of lung metastasis and chemotherapy are. It is not necessary to worry about lung metastasis before evacuation of HM, the outcome of post-chemotherapy is very good.

Ultrasound is the modality of choice for evaluating normal or abnormal first trimester pregnancy. Sonography can usually provide a specific diagnosis in abnormal first trimester bleeding. When the sonographic appearance is correlated with the clinical presentation, accurate diagnosis is possible in most cases of gestational trophoblastic disease (GTD). Partial or complete hydatidiform moles can be diagnosed in early gestation. However certain cases will be missed if the curettage material is not sent for pathologic examination. Sometimes molar pregnancies have very unusual sonographic appearances. Sonography and Doppler imaging are helpful in diagnosing gestational trophoblastic disease, in determining whether invasive disease is present, in detecting recurrent disease, and in following the effectiveness of chemotherapy. This pictorial essay describes the pathogenesis, epidemiology, and sonographic spectrum of gestational trophoblastic disease.

Leptin is a protein hormone synthesized and secreted by adipose tissue and also probably in other organs and systems in human body. It has multiple functions such as to regulate feed intake and energy balance, gonadal regulation, action in the hypothalamo-pituitary-gonadal axis, regulates the metabolism of the fetal-placental unit in the pregnancy, fertility and reproductive systems, actions in the endometrium, mammary gland with corresponding influences on important physiologic processes such as menstruation, pregnancy and lactation. In the gynecologic surgery the serum leptin concentration is also modified. The knowledge of serum leptin concentration in the oncological diseases is going-up. Leptin is modified in the choriocarcinoma, Meigs' syndrome and other tumors. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with abnormalities of fetal maturity and development, general concept growth, trophoblast endocrinology, and placental sufficiency. Further investigations in this area will be necessary to improve new knowledge and a better understanding of the actions about this hormone.

Objective: To assess whether a complete hydatidiform mole (CHM) carries an increased risk of later requiring chemotherapy in pregnancies continued to term., Study Design: The Charing Cross gestational trophoblastic neoplasia (GTN) database was screened between 1973 and 2002 to identify registered singleton CHMs with a known gestational age at the time of evacuation. Of the 8,313 cases 2,800 were centrally histopathologically reviewed by us and confirmed as CHM. The proportion of patients requiring chemotherapyfor both total registered and centrally reviewed patients was analyzed by trimester of evacuation (< 13, 13-24, > 24 weeks). Statistical significance was assessed by the chi2 test., Results: For the total population, including non-centrally reviewed patients, evacuation occurring in the first, second or third trimester was associated with a treatment rate of 13.9% (601 of 4,333), 10.8% (412 of 3,803) and 5.1% (9 of 177), respectively. In patientsfor whom a central pathologic review had been performed to confirm the diagnosis, the treatment rates were 27.7% (525 of 1,897), 27% (241 of 893) and 20% (2 of 10). The higher apparent treatment rates reflect an error in the denominator as we do not review all nontreated cases. In the total population, evacuation in the third trimester correlated with a reduction in risk of subsequent treatment (P<.001). Most of these late deliveries were induced (before adequate ultrasound), whereas the earlier pregnancies were mostly terminated via suction dilatation and curettage., Conclusion: There is no evidence that delayed evacuation/delivery of singleton CHM increases the risk of subsequently requiring chemotherapy.

Gestational trophoblastic diseases are interrelated conditions characterized by abnormal growth of chorionic tissues with varying propensitiesfor local invasion and metastases. These diseases are characterized by altered expression of several growth regulatory factors and oncogenes. On the basis of the expression of various oncogenes and growth factors, partial mole appears to be more like normal placenta, while complete mole seems to be more like choriocarcinoma. These results may have both prognostic and therapeutic consequences and provide insight into the relationship between normal placenta and gestational trophoblastic diseases.

A case is reported of a patient who presented to his family doctor with a short history of cough with signs and symptoms of thyrotoxicosis. Carbimazole treatment had little effect and his symptoms worsened to include severe shortness of breath. He was investigated further and found to have multiple lung and liver metastases from an unknown primary site. Biopsy and subsequent post-mortem investigations revealed a testicular tumour and a grossly elevated serum human chorionic gonadotrophin (hCG) concentration. The biochemical and clinical thyrotoxicosis is presumed to be due to the thyrotrophic activity of excess hCG secretion, in a situation analogous to that seen in hydatidiform mole or in hyperemesis gravidarum.

Objective: To study the relationship between malignant transformation and fertilization types of hydatidiform moles (HM)., Methods: Fifty four HM specimens were analyzed by using multiplex STR-PCR (9 loci) to determine the fertilization types and all patients were followed-up for the human chorionic gonadotropin (hCG) over 1 year., Results: Total malignant transformation cases were 10 in all the 54 HM. Ggenetics complete hydatidiform moles (g-CHM) with DNA from only paternal origin, were observed in 38 cases including 28 homozygote and 10 heterozygote cases. In homozygote and heterozygote cases,malignant transformation occurred in 8 cases of the empty eggs fertilized by single sperms and 2 by double sperms respectively. In all the 54 HMs, 16 cases of DNA from parents were genetic partial hydatidiform moles (g-PHM), and no malignant transformation occurred in each haploidy egg fertilized by double sperms., Conclusion: (1)Genetic complete hydatidiform moles (g-CHM) showed a higher malignant transformation risk than genetic partial hydatidiform moles (g-PHM) (P=0.024 2); (2)There was no significant difference in malignant transformation between homozygote and heterozygote of g-CHM (P=0.699).

Objectives: To study the correlation between Doppler blood flow and beta-human chorionic gonadotropin (hCG), to assess the course of the disease and the follow up evaluation., Setting: This study was conducted in Assiut University Hospital, Department of Obstetrics and Gynecology., Design: Longitudinal study., Subjects and Methods: Fifteen cases of vesicular mole were recruited and followed up. The patients were evaluated the day before evacuation of the uterus. This included clinical assessment, Doppler uterine artery blood flow velocity waveforms using the Doppler indices and assessment of the serum level of beta-hCG. These cases were followed up every 2 weeks in the first 2 months, and every month thereafter until the 6 month., Results: Twelve patients showed continuous decrease in beta-hCG level from 1192+/-697 to 6+/-11 IU/ml by the end of the second month. Systolic-diastolic (S/D) increased from (2.57+/-1.13) to (15.9+/-2.07) (P<0.0001), RI increased from 0.55+/-0.15 to 1.0+/-0.26(P<0.0001) and PI increased from 1.02+/-0.47 to 6.12+/-2.34 (P<0.0001). One patient showed a fluctuating level of beta-hCG around the same level, and two showed a slowed decrease. Doppler indices showed similar results. There is a strong correlation between beta-hCG and all Doppler indices throughout the course of follow up: beta-hCG and S/D r<0.01, beta-hCG and RI r<0.01 and beta-hCG and PI r<0.01., Conclusion: Doppler ultrasound can be used as an adjuvant tool in the follow up of cases of vesicular mole and can predict the progress in the course of the disease.

Objective: The aim of this study was to determine the oxidative status and antioxidative status of plasma of patients with complete hydatidiform mole (CHM) and to compare these values with normal pregnancy., Method: Thirty-eight patients with CHM and 31 healthy pregnant women were enrolled in the study. To determine the antioxidative status of plasma, total antioxidant potential (TAOP) was calculated, and to determine the oxidative status of plasma total peroxide levels were measured. The ratio of TAOP to total peroxide was accepted as an indicator of oxidative stress., Results: TAOP of plasma was significantly lower in patients with hydatidiform mole than in healthy pregnant women [mean (SD) values were 511.9 (105.8) and 571.7 (109.4) micromol Trolox equiv./L respectively (p <0.05)]. In contrast, mean (SD) total peroxide level of plasma was significantly higher in the patients [21.8 (6.4) micromol H2O2/L] than in healthy pregnant women [15.6 (6.4) micromol H2O2/L (p <0.001)]. The mean oxidative stress index level was significantly higher in patients with CHM than in healthy pregnant women [4.43 (1.70) versus 2.92 (1.50) respectively (p <0.001)]., Conclusion: Patients with CHM are exposed to oxidative stress, which may have a role in the pathogenesis of the disease. Supplementation with antioxidative vitamins such as C and E could be considered in treatment.

We report a rare case of a complete hydatidiform mole with two or more coexisting fetuses where both infants survived without complications. A male infant weighing 1258 g and a female infant weighing 880 g were delivered without complications and discharged 95 days after the birth. The analysis of DNA microsatellite polymorphisms indicated that the mole was of paternal origin and probably homozygous. The mother suffered from multiple pulmonary metastasis of the hydatidiform mole which was detected 3 days after the surgery and was successfully treated with methotrexate. A complete hydatidiform mole with two or more coexisting fetuses produces a dilemma between immediate termination and pregnancy continuation. Although the present case resulted in a favorable outcome, a review of the 14 reported cases suggests that the high fetal loss rate (90%) must be a consideration in the decision regarding management of such a pregnancy.

Hydatidiform molar change, characterized by abnormal fetoplacental development and placental villous trophoblast hyperplasia, results from genetically abnormal conception, in which there is an excess of paternally derived genetic material. The majority of pregnancies in which molar change has been reported in association with a live fetus represent dizygotic twin pregnancies in which one fertilization results in a complete hydatidiform mole (CM) and the other a normal co-twin. In such cases, there is usually a clear distinction, both sonographically and pathologically, between the molar and non-molar regions of the placenta. We present a singleton pregnancy, with diffuse placental molar change detected prenatally, which resulted in a chromosomally and phenotypically normal female infant at term. Pathological examination revealed the presence of intermixed populations of morphologically normal chorionic villi and villi with the characteristics of CM. Studies of genetic polymorphisms demonstrated that the CM, normal villi and fetus were all derived from the same sperm; the fetus was diploid and biparental whereas the areas of pathological CM were androgenetic and monospermic. We believe this represents the first well-documented case of apparent confined placental mosaicism involving CM and a coexisting normal fetus, which has presumably arisen following mitotic abnormalities in the early post-fertilization period.

The partial hydatidiform mole is a histopathologic entity characterized by focal trophoblastic hyperplasia with villous hydrops together with identifiable fetal tissue which was first described by Szulman and Surti in 1978. Since then major advances in molecular biology have shown that more than 90 per cent of partial moles are secondary to diandric triploidy and that this condition accounts for most cases of persistent trophoblastic disease after partial mole. Case series describing the prenatal diagnosis of triploid partial mole were reviewed and outcomes were analysed for all pregnancies, and compared to those of non-molar triploidy using the chi-square test. In more than 90 per cent of both types of triploidy, the fetus shows growth restriction and multiple structural anomalies. Oligohydramnios and abnormal placental Doppler indices are common in both types. In triploid partial mole, 82.1 per cent of fetuses present with symmetrical growth restriction, the maternal serum human chorionic gonadotropin (MShCG) level is increased in 80.8 per cent of the cases and 41.9 per cent of the women are at risk of pre-eclampsia. The triploid partial mole is a lethal fetal condition which is linked with gestational trophoblastic disorders. The typical placental molar features are not always pathognomonic of triploid partial mole and are less likely to be apparent on ultrasound in early pregnancy. The perinatal diagnosis of this condition relies upon mainly on MShCG level and cytogenetic results which have to be correlated with the histopathologic diagnosis. Women with this pregnancy complication should be offered immediate termination and a specific follow-up., (Copyright 1999 W.B. Saunders Company Ltd.)

There is abundant evidence that human chorionic gonadotropin (hCG) is a weak thyrotropin (TSH) agonist. In FRTL-5 rat thyroid cells, hCG increases cyclic adenosine monophosphate (cAMP), iodide transport, and cell growth. hCG has thyroid-stimulating activity in bioassays in mice and in clinical studies in man. In cultured cells transfected with the human TSH receptor, hCG increases generation of cAMP. Molecular variants of hCG with increased thyrotropic potency include basic molecules with reduced sialic acid content, truncated molecules lacking the C-terminal tail, or molecules in which the 47-48 peptide bond in the beta-subunit loop is nicked. In normal pregnancy, when hCG levels are highest at 10 to 12 weeks gestation, there is suppression of serum TSH levels, presumably due to slight increases in free thyroxine (T4) concentration. In twin pregnancies, hCG levels tend to be higher and suppressed TSH levels are more frequent. Hyperemesis gravidarum, defined as severe vomiting in early pregnancy that causes 5% weight loss and ketonuria, is usually associated with increased hCG concentration. A high proportion of patients with hyperemesis gravidarum, about one-third to two-thirds in different series, have evidence of increased thyroid function. Only a small proportion of these patients have clinical hyperthyroidism, termed gestational thyrotoxicosis. These patients probably secrete a variant of hCG with increased thyroid-stimulating activity. Trophoblastic tumors, hydatidiform mole, and choriocarcinoma often cause hyperthyroidism because they secrete very large amounts of hCG. When the serum hCG exceeds about 200 IU/mL, hyperthyroidism is likely to be found. There is a correlation between the biochemical severity of hyperthyroidism and the serum hCG in these patients. Removal of the mole or effective chemotherapy of the choriocarcinoma cures the hyperthyroidism. In conclusion, hCG has thyroid-stimulating activity that influences thyroid function early in pregnancy when hCG levels are high. Excessive hCG secretion may cause hyperthyroidism in patients with hyperemesis gravidarum or trophoblastic tumors.

Background: Multiple pregnancies consisting of a complete hydatidiform mole and coexisting fetuses are relatively rare but may become more common due to the increasing use of ovulation-induction agents., Cases: We report on a twin and a triplet pregnancy, conceived using clomiphene citrate, with contrasting outcomes. The twin pregnancy resulted in a term delivery of a healthy singleton and the triplet pregnancy in a termination at 17 weeks followed by the development of choriocarcinoma., Conclusion: The few cases available suggest that a subgroup of complete moles follows a more benign course and can be managed conservatively, allowing the pregnancy to go to term with appropriate follow-up, whereas other cases follow a more aggressive course. Larger case series are needed to develop definitive protocols.

Gestational trophoblastic diseases are a heterogeneous pool of clinically and histopathologically defined entities with two clinically relevant features: reproductive failure and a high neoplastic potential. Here we review recent advances in understanding the biology and natural history of the most common form of trophoblastic disease, hydatidiform mole, with an emphasis on the clinical implications for patient management. There are no reliable genetic markers for predicting which subset of moles will behave aggressively, nor are there molecular diagnostic methods at present that offer advances over traditional histopathology. The predominant genetic finding in complete and partial hydatidiform moles is an imbalance of parental chromosomes, completely androgenetic (paternal) in the former and an extra paternal haploid set in the latter. This lack or imbalance of a maternal genomic contribution probably changes the gene expression since there is no evidence of gene mutation in these lesions.

Transvaginal color Doppler ultrasonography was used to study 131 normal early pregnancies, 30 molar pregnancies, 20 threatened abortions, two blighted ova, and five pregnancies with intramural myoma. Four separate parts of the maternal circulation were studied: uterine, arcuate, radial, and spiral arteries. There was statistical difference in the RI and PI among uterine, arcuate, radial, and spiral arteries (P < 0.001) in all observed groups of patients except those with intramural myoma. When the same part of the maternal circulation was compared among different groups of patients, the following results reached statistical significance: uterine artery in normal and molar pregnancy (P < 0.001); arcuate artery in normal and molar pregnancy (P < 0.001); radial artery in normal and molar pregnancy (P < 0.001) and in normal pregnancy and threatened abortion (P < 0.01); spiral artery in normal and molar pregnancy (P < 0.001), in normal pregnancy and threatened abortion (P < 0.01), and in molar pregnancy and threatened abortion (P < 0.01). The standard values of blood flow are different in normal and in some cases of abnormal early pregnancy (molar pregnancy, threatened abortion).

Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed.

To determine the epidemiological and clinicopathological characteristics of partial hydatidiform mole (PHM), a comparative study of PHM and complete hydatidiform mole (CHM) was performed in molar patients who were entered in the regional registry of Niigata Prefecture and/or who were admitted for treatment at Niigata University Hospital. The results obtained are as follows. 1. From 1971 to 1988, 2,290 hydatidiform moles (HMs) were documented in the registry. The incidence of HM was annually decreasing with an almost constant ratio to the total number of pregnancies. Since 1986, the number of PHM was rising with an inverse decrease in CHM. One hundred fifty one of 1,923 CHM (7.9%) had persistent trophoblastic disease (PTD), but on the other hand only 6 of 367 cases PHM (1.6%) had. 2. In 275 patients treated in our hospital from 1971 to 1990, 134 of 240 with CHM (55.8%) and 6 of 35 with PHM (17.1%) experienced PTD. Of 6 PTD patients following PHM, 3 had invasive mole, 1 metastatic mole and 2 post molar persistent hCG, but no choriocarcinoma. 3. The recent study of DNA analysis in molar tissue revealed that one case, which had been diagnosed as PHM, coexisted with CHM and non-molar pregnancy.

Clinical information and histopathologic material for 165 patients with hydatidiform mole referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School during one year were reviewed in order to identify characteristics more likely to be associated with the development of gestational trophoblastic tumors. Twenty-nine patients (18%) required chemotherapy for invasive mole or choriocarcinoma. Patients with uterine enlargement beyond that expected for dates and patients with ovarian theca-lutein cysts were much more likely to require treatment after molar evacuation (47% vs. 18% and 40% vs. 16%, respectively). There was no correlation between the initial human chorionic gonadotropin level, gestational age, uterine size per se, maternal age or gravidity and the subsequent clinical course. Histologically, the following factors were associated with an increased incidence of postmolar gestational trophoblastic tumor: (1) progressive nuclear atypia (26.7% if atypia present vs. 40% if absent); (2) necrosis and hemorrhage (39.1% if extensive vs. 12.8% if limited); (3) decreased trophoblast maturation (48% if less than 20% mature vs. 8.7% if greater than or equal to 20% mature); (4) trophoblast proliferation (50% if marked vs. 13.9% if limited); (5) increased ratio of cytotrophoblast to syncytium (33.3% if greater than 1 vs. 6.4% if less than 1); and (6) absence of Nitabuch's layer (21.4% if absent vs. 11.6% if present). Hydatidiform moles which demonstrate clinical or histopathologic evidence of excessively abnormal proliferative activity, as indicated by these features, are more likely to develop invasive mole or choriocarcinoma and should be considered for prophylactic chemotherapy.