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Complete hydatidiform mole of our case (haematoxylin-eosin stain, magnification × 100) (villus edema, hyperplasia of trophoplastic tissue, mild nuclear atypia)
Source publication
Benign hydatidiform mole, complete or partial, is the most common type of gestational trophoblastic disease (GTD) characterised by excessive trophoblastic proliferation and abnormal embryonic development. Although most complete hydatidiform moles (CHMs) are diploid androgenetic, a few cases of CHMs are biparental, characterised by recurrence and fa...
Citations
... Hydatidiform mole during pregnancy including partial hydatidiform mole (PHM) and complete hydatidiform mole (CHM) with a normal fetus have been described. At the cytogenetic level, more than 90% of PHMs are triploids formed by double spermatozoa and one ovum, i.e., one chromosome from the mother and two from the father (Kalogiannidis et al., 2018). In CHMs, 80% to 90% of spermatozoa are haploid, i.e., fertilized with a chromosomally inactivated ovum or an empty ovum, or a chromosomally inactivated ovum or an empty ovum fertilized by a diploid sperm from a failed second meiosis (Vassilakos et al., 1977). ...
Hydatidiform mole and coexisting fetus is a very rare condition of which etiology is still inconclusive. It may occur after assisted reproduction, often leading to the death of normal embryos and other serious complications. We report a case of partial hydatidiform mole and coexisting fetus after frozen embryo transplantation. More than two months after the patient underwent transplantation with two blastocysts (scored 4AB and 4BC), B-ultrasound showed a single live fetus with a large dense dotted strong echo area. The patient was treated with chemotherapy after the termination of pregnancy due to persistently increased human chorionic gonadotropin levels. Many studies have described trophoblast quality as a strong predictor of pregnancy. In the case in question, in addition to partial hydatidiform mole caused by multiple sperm entering the egg, we also speculate that the condition may be related to the poor quality of the trophoblastic ectoderm of the transferred embryo. In the process of assisted reproduction, the transfer of embryos with poor trophoblastic ectoderm in multiple embryo transfers may adversely affect pregnancy outcomes.
... A recurrent hydatidiform mole (RHM) is a rare form of the complete hydatidiform mole, being discovered in less of 1% of all cases of complete hydatidiform moles. This disorder is characterized by the occurrence of two or more molar pregnancies in the same patient [26]. RHMs can be isolated or familial. ...
A hydatidiform mole (HM) or molar pregnancy is the most common benign form of gestational trophoblastic disease characterized by a proliferation of the trophoblastic epithelium and villous edema. Hydatidiform moles are classified into two forms: complete and partial hydatidiform moles. These two types of HM present morphologic, histopathologic and cytogenetic differences. Usually, hydatidiform moles are a unique event, but some women present a recurrent form of complete hydatidiform moles that can be sporadic or familial. The appearance of hydatidiform moles is correlated with some genetic events (like uniparental disomy, triploidy or diandry) specific to meiosis and is the first step of embryo development. The familial forms are determined by variants in some genes, with NLRP7 and KHDC3L being the most important ones. The identification of different types of hydatidiform moles and their subsequent mechanisms is important to calculate the recurrence risk and estimate the method of progression to a malign form. This review synthesizes the heterogeneous mechanisms and their implications in genetic counseling.
... Molar pregnancy, including complete and partial mole, is the most frequent type of Gestational trophoblastic disease (GTD) which is a spectrum of pregnancy-associated lesions characterized by trophoblastic proliferation [1,2] . The incidence of GTD varies across countries worldwide, with Asia exhibiting the highest rates [2] . ...
... Molar pregnancy, including complete and partial mole, is the most frequent type of Gestational trophoblastic disease (GTD) which is a spectrum of pregnancy-associated lesions characterized by trophoblastic proliferation [1,2] . The incidence of GTD varies across countries worldwide, with Asia exhibiting the highest rates [2] . Several factors can be involved in this variety, including heterogeneity and dietary causes [1] . ...
Introduction and Importance
Molar pregnancy is the most common type of gestational trophoblastic disease. It manifests as vaginal bleeding, accompanied by high levels of β-HCG. This case aims to highlight the importance of considering gestational trophoblastic disease as a potential diagnosis and its serious complications.
Case Presentation
A 24-year-old female presented with vomiting, nausea, and no complaint of vaginal bleeding. Laboratory tests indicated hyperthyroidism as a complication requiring challenging preoperative prophylactic management. Initially, the patient underwent suction and curettage, but a total hysterectomy had to be performed later. The histological study concluded with the diagnosis of a complete hydatidiform mole. Post-surgery follow-up evaluations revealed high blood pressure values, and the patient was appointed for further cardiology assessment.
Discussion and Conclusion
Although uncommon, complications of a molar pregnancy include anemia, severe cardiac distress, and hyperthyroidism. Trophoblastic Hyperthyroidism is a result of extremely high levels of β-HCG levels due to molecular cross-reactivity. History, clinical examination, and ultrasound, in addition to measuring β-HCG levels, could all help in diagnosing a molar pregnancy, but the definitive diagnosis is based on histopathology and a karyotype study. Management procedures include dilation, suction & curettage, and hysterectomy. The treatment depends on the patient’s age, desire for future pregnancies, and risk of developing gestational trophoblastic neoplasia. A follow-up with serial β-HCG measurement is recommended to monitor possible complications. Attaining and maintaining euthyroidism is a life-saving procedure before molar pregnancy surgery. Methimazole, Propranolol, Lugol’s iodine, and hydrocortisone can all be used in the prophylactic management of the thyroid storm.
... Some experts suggest that in cases with RHM it is necessary to do DNA testing if there is a genetic mutation in NLRP7 or KHDC3L, then oocyte donation needs to be done to increase the chances of a normal pregnancy. 18 It is because genetic mutations of NLRP7 and KHDC3L are considered to have a role in the occurrence of increased incidence of RHM. 8,19 Conclusions The incidence of recurrent PHM is rare. ...
Hydatidiform mole (HM) is an aberrant pregnancy characterized by atypical trophoblastic hyperplasia, hydropic chorionic villi, and deprived fetal development. There are two types of HM, ie, complete (CHM) and partial (PHM). Both CHM and PHM can recur; however, the recurrence of PHM is very scarce compared to CHM. In this report, we present a case of a 33-year-old woman with recurrent PHM for 7 times without any normal pregnancy in-between. PHM was determined by histology examination. The patient underwent suction curettage and was followed up with serial β-hCG levels. Recurrent PHM, although rare, is associated with an increased incidence of malignancy. A series of clinical and β-hCG evaluation should be warranted because of the possibility of gestational trophoblastic neoplasia development.
... Genetic anomalies in the sperm or the ovum are frequently blamed for abnormal fertilization that results in the development of a full or partial mole [2]. NLRP7 and KHDC3L gene mutations, for example, have been linked to an increased risk of molar pregnancy [3]. Molar pregnancy may also develop as a result of environmental factors. ...
With a focus on its prevalence, risk factors, clinical characteristics, diagnostic techniques, management approaches, and outcomes, this paper aims to provide a thorough overview of molar pregnancy. It will be possible to gain important insights into the causes of molar pregnancy and their contributing factors by looking at the literature and research studies that have already been done. The results emphasize the value of early identification, suitable management, and preventive measures for this uncommon pregnancy complication. When compared to typical pregnancies, the prevalence of molar pregnancy is relatively low, with estimates ranging from 1 in 468 to 1 in 714 pregnancies. The reasons for these variations in prevalence rates include study populations, methodologies, and geographic considerations. Maternal advanced age and a history of molar pregnancy have both been identified as risk factors for molar pregnancy. Environmental elements like nutritional deficiencies and exposure to high altitudes, as well as genetic abnormalities in the sperm or egg, may also play a role in the development of molar pregnancy.
... 3 It has been determined that the recurrent hydatidiform mole, which is pathologically indistinguishable from the androgenetic complete hydatidiform mole, has a two-parent genotype. 4 This unusual picture is often associated with families with a hereditary predisposition to molar pregnancies. 5 Genetic studies on these families have identified the basic maternal recessive locus for familial recurrent hydatidiform moles and the gene NALP7 that causes it in 19 q13.4. ...
Hydatidiform moles are the most common type of gestational trophoblastic neoplasia. Hyperproliferative vesicular trophoblasts and imperfect fetal development are abnormal pregnancies, and recurrent hydatidiform moles are rare. Mutations in NLRP7 are responsible for recurrent hydatidiform mole. Genetic heterogeneity has been demonstrated in patients with the NLRP7 mutation. This study presents our case with gravida 11, parity 0, histopathologically diagnosed with six hydatidiform moles and five missed abortion histories at age 35. Karyotype analyses of the unrelated couple were normal. A genetic examination revealed a novel mutation of the NLRP7 gene in the patient, his brother, and his parents. Detecting a new NLRP7 mutation in recurrent hydatidiform moles cases provides further evidence for the predetermined role of NLRP7 mutations in the pathophysiology of recurrent moles hydatidiform. Based on our findings, we hope to contribute to the literature by expanding the spectrum of recurrent pregnancy loss associated with NLRP7 mutations in patients.
... Furthermore, it appears that, in women who have at least two episodes of molar pregnancy, reproductive options are currently limited, while assisted reproductive technology may help to achieve normal fertilisation of oocytes [20]. A recent case report presents a case of oocyte donation performed in a patient affected by five spontaneous pregnancies with a negative outcome: a spontaneous miscarriage and four CHM, with a genetic test carried out with two heterozygous mutations in the NLRP7 gene. ...
Hydatidiform mole, complete or partial (CHM/PHM), is the most common type of gestational trophoblastic disease (GTD), which is characterized by excessive trophoblastic proliferation and abnormal embryonic development. Some patients present with sporadic or familiar recurrent hydatidiform moles (RHMs), which are characterized by two or more episodes of the disease. A healthy 36-year-old woman was admitted to the Obstetrics and Gynecology Unit of Santa Maria Goretti Hospital, Latina, because of RHMs at 6 weeks of amenorrhea, with an obstetrical anamnesis of RHMs. We performed uterine dilatation and curettage with suction evacuation. The histological examination confirmed the diagnosis of PHM. The clinical follow-up was conducted according to recent guidelines on the diagnosis and management of GTD. After the return to the baseline values of the beta-human chorionic gonadotropin hormone, a combined oral contraceptive therapy was proposed, and the patient was invited to undergo in vitro fertilization (IVF) techniques, specifically oocyte donation, to reduce the possibility of similar future cases of RHMs. Although some etiopathogenetic mechanisms involved in RHMs are still unknown, all patients of childbearing age who are affected by this syndrome should be properly treated and directed towards a correct clinical path as IVF, to have a successful and safe pregnancy.
... Previous studies have reported a link between NLRP7 variants and recurrent hydatidiform mole (RHM), a rare autosomal recessive disease that is defined as two or more hydatidiform mole pregnancies in the same patient where the genotype of HM tissues is diploid biparental or triploid digenic [15,16]. Hydatidiform mole is characterized by defective embryo development and excessive proliferation of the trophoblast, which result in reproductive wastage or development into choriocarcinoma (CC) [17,18]. CC is a malignant tumor and its cells can metastasize to other organs, eventually leading to maternal death [19]. ...
Successful human reproduction requires normal oocyte maturation, fertilization, and early embryo development. Early embryo arrest is a common phenomenon leading to female infertility, but the genetic basis is largely unknown. NLR family pyrin domain-containing 7 (NLRP7) is a member of the NLRP subfamily. Previous studies have shown that variants of NLRP7 are one of the crucial causes of female recurrent hydatidiform mole, but whether NLRP7 variants can directly affect early embryo development is unclear. We performed whole-exome sequencing in patients who experienced early embryo arrest, and five heterozygous variants (c.251G > A, c.1258G > A, c.1441G > A, c. 2227G > A, c.2323C > T) of NLRP7 were identified in affected individuals. Plasmids of NLRP7 and subcortical maternal complex components were overexpressed in 293 T cells, and Co-IP experiments showed that NLRP7 interacted with NLRP5, TLE6, PADI6, NLRP2, KHDC3L, OOEP, and ZBED3. Injecting complementary RNAs in mouse oocytes and early embryos showed that NLRP7 variants influenced the oocyte quality and some of the variants significantly affected early embryo development. These findings contribute to our understanding of the role of NLRP7 in human early embryo development and provide a new genetic marker for clinical early embryo arrest patients.
Key messages
Five heterozygous variants of NLRP7 (c.1441G > A; 2227G > A; c.251G > A; c.1258G > A; c.2323C > T) were identified in five infertile patients who experienced early embryo arrest.
NLRP7 is a component of human subcortical maternal complex.
NLRP7 variants lead to poor quality of oocytes and early embryo development arrest.
This study provides a new genetic marker for clinical early embryo arrest patients.
... FRHMs are mostly BiCHMs, in contrast to androgenetic CHMs [5]. BiCHMs are caused by homozygous pathogenic variations in the maternal genotype and the paternal genotype is not involved in pathogenesis [6]. The two most frequently involved maternal gene loci are NLRP7 and KHDC3L, causing 75-80% and 5-10% of FRHM cases, respectively [5]. ...
... These syndromes are termed HYDM1 (OMIM#231090) when caused by mutations in the NLRP7 gene and HYDM2 (OMIM#614293) when caused by mutations in the KHDC3L gene [7]. For cases with FRHM, in vitro fertilization with oocyte donation may be offered, but even then, HM and subsequent failure of achieving normal pregnancy may occur [6]. ...
Objective
Pathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.
Material and Methods
Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of NLRP7 and KHDC3L genes.
Results
NLRP7 pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the KHDC3L gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.
Conclusions
We found that defects of the NLRP7 gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.
... NLRP7 was the first identified maternal effect gene implicated in recurrent hydatidiform mole (RHM) and 48-80% of patients with recurrent molar pregnancies were found to have mutations in the NLRP7 gene [3]. It has also been implicated in other forms of reproductive wastage such as spontaneous abortions, stillbirths, and intrauterine growth retardation [4,5]. ...
PurposeThe genetic alteration in NLRP7 and KHDC3L genes causes recurrent familial molar pregnancy and poor reproductive outcomes. The aim of this study was to determine the association of genetic aberrations with recurrent molar pregnancy and related reproductive outcome.
Method
The genetic testing of NLRP7 and KHDC3L was performed in clinically diagnosed cases of molar pregnancy.Result and Conclusion
In this case series of six women with recurrent pregnancy loss and one or more molar pregnancies, none of them had a significant family history of disease. Moreover, three women had two molar pregnancies. NLRP7 pathogenic variants were identified in three patients with two or more molar pregnancies, out of which one variant was common in two patients belonging to similar ethnicity. Two of them had developed gestational trophoblastic neoplasia. On follow-up, only those patients with single molar pregnancy and negative for variants had successful reproductive outcomes. This report suggests the likelihood of identifying NLRP7 mutations is high in those with two or more molar pregnancies and increases the risk of gestational trophoblastic neoplasia.
