BACKGROUND: Chemotherapy is crucial in treating gestational trophoblastic neoplasia (GTN), but its impact on gonadotoxicity is unclear.
METHODS: This case-control study included 57 GTN patients and 19 age-matched patients with molar pregnancies (MP) in 2012-2018. Multiples of the median (MoM) of the serum AMH levels were compared between the two groups, and between patients using single-agent and combination chemotherapy, at baseline, 6, 12, and 24 months after treatment. Their pregnancy outcomes were also compared.
RESULTS: There was no significant difference in the MoM of serum AMH between GTN and MP groups at all time points. Single-agent chemotherapy did not adversely affect the MoM. However, those receiving combination chemotherapy had lower MoM than those receiving single-agent chemotherapy at all time points. The trend of decline from the baseline was marginally significant in patients with combination chemotherapy, but the drop was only significant at 12 months (Z = -2.69, p = 0.007) but not at 24 months (Z = -1.90; p = 0.058). Multivariable analysis revealed that combination chemotherapy did not affect the MoM. There was no significant difference in the 4-year pregnancy rate and the livebirth rate between the single-agent and combination groups who attempting pregnancy, but it took 1 year longer to achieve the first pregnancy in the combination group compared to the single-agent group (2.88 vs. 1.88 years).
CONCLUSIONS: This study showed combination chemotherapy led to a decreasing trend of MoM of serum AMH especially at 12 months after treatment, but the drop became static at 24 months. Although pregnancy is achievable, thorough counseling is still needed in this group especially those wish to achieve pregnancy 1-2 years after treatment or with other risk factors.

UNASSIGNED: Vitamin D receptor (VDR) exerts anti-cancer properties in a variety of cancers. The purpose of this study was to investigate the expression of VDR in patients with hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN).
UNASSIGNED: This is a cross-sectional study involved 61 specimens of HM (n = 37, 60.7%) and GTN (n = 24, 39.3%) was collected from the biopsy. An immunohistochemistry was used to asses the VDR expression. Student\'s t-test and Mann-Whitney test were used to compare the expression of VDR, including VDR staining intensity, VDR distribution, and histoscore, between HM and GTN tissue specimens.
UNASSIGNED: No significant differences in age and parity were noted between patients with HM or GTN (p > 0.05). The VDR staining intensity of GTN tissue specimens was significantly lower than that of HM tissue specimens (2.3 ± 0.8 vs. 2.8 ± 0.5, p = 0.008). In addition, the histoscore for GTN tissues was significantly lower than that for HM tissues (7.3 ± 3.2 vs. 9.4 ± 28, p = 0.016). However, no significant differences in VDR distribution between GTN and HM tissues were observed (3.3 ± 0.8 vs. 3.3 ± 1.0, p = 0.525).
UNASSIGNED: Low VDR expression is associated with GTN, whereas high VDR expression is associated with HM, suggesting that the expression of VDR may regulate the severity of gestational trophoblastic disease.
UNASSIGNED: لدى مستقبلات فيتامين د أدوار كمضاد للسرطان لأنواع مختلفة من السرطانات. الهدف من هذه الدراسة هو تحديد الفروق في مستويات مستقبلات فيتامين د بين الورم الحويصلي المائي وورم النسيج الترويفي الحملي.
UNASSIGNED: هذه دراسة مقارنة شملت ستة وستين نسيجا تم جمعها من الورم الحويصلي المائي وورم النسيج الترويفي الحملي. تم إجراء اختبار \"تي\" واختبار \"مان ويتني\" لمقارنة التعبير المناعي لمستقبلات فيتامين د، بما في ذلك شدة مستقبلات فيتامين د، توزيع مستقبلات فيتامين د، والتقدير التاريخي بين الورم الحويصلي المائي وورم النسيج الترويفي الحملي.
UNASSIGNED: تم تضمين ما مجموعه ستة وستين عينة من الأنسجة في هذه الدراسة، تتألف من سبعة وثلاثين نسيجا تم تشخيصها بالورم الحويصلي المائي وأربعة وعشرين نسيجا تم تشخيصها بورم النسيج الترويفي الحملي. تمت المقارنة بين العمر والأعداد بين المرضى الذين يعانون من الورم الحويصلي المائي والمرضى الذين يعانون من ورم النسيج الترويفي الحملي، ولم يلاحظ وجود فروقات كبيرة في كلا المجموعتين. بالنسبة لحالات ورم النسيج الترويفي الحملي، كانت شدة مستقبلات فيتامين د أقل بشكل ملحوظ من شدة مستقبلات فيتامين د في نسيج الورم الحويصلي المائي. بالإضافة إلى ذلك، كان التقدير التاريخي في نسيج ورم النسيج الترويفي الحملي أقل بشكل ملحوظ من التقدير التاريخي في نسيج الورم الحويصلي المائي. ومع ذلك، لم يكن هناك فروقات كبيرة في توزيع مستقبلات فيتامين د بين نسيج ورم النسيج الترويفي الحملي ونسيج الورم الحويصلي المائي.
UNASSIGNED: كان التعبير المنخفض لمستقبلات فيتامين د مرتبطا بورم النسيج الترويفي الحملي. بالمقابل، كان التعبيرالعالي لمستقبلات فيتامين د مرتبطا بالورم الحويصلي المائي. تشير هذه النتائج إلى أن مستويات مستقبلات فيتامين د قد تلعب دورا في شدة مرض النسيج الترويفي الحملي.

UNASSIGNED: Hydatidiform moles (HM) are members of gestational trophoblastic diseases (GTD) and, in some cases, might progress to gestational trophoblastic neoplasia (GTN). HMs are either partial (PHM) or complete (CHM). Some HMs are challenging in arriving at a precise histopathological diagnosis. This study aims to investigate the expression of BCL-2 by immunohistochemistry (IHC) in HMs as well as in normal trophoblastic tissues \"products of conception (POC) and placentas\" using Tissue MicroArray (TMA) technique.
UNASSIGNED: TMAs were constructed using the archival material of 237 HMs (95 PHM and 142 CHM) and 202 control normal trophoblastic tissues; POC and unremarkable placentas. Sections were immunohistochemically stained using antibodies against BCL-2. The staining was assessed semi-quantatively (intensity and percentage of the positive cells) in different cellular components (trophoblasts and stromal cells).
UNASSIGNED: BCL-2 showed cytoplasmic expression in more than 95% of trophoblasts of PHM, CHM and controls. The staining showed a significant reduction of the intensity from controls (73.7%), PHMs (76.3%) to CHM (26.9%). There was a statistically significant difference between PHM and CHM in the intensity (p-value 0.0005) and the overall scores (p-value 0.0005), but not the percentage score (p-value > 0.05). No significant difference was observed in the positivity of the villous stromal cells between the different groups. All cellular components were visible using the TMA model of two spots/case (3 mm diameter, each) in more than 90% of cases.
UNASSIGNED: Decreased BCL-2 expression in CHM compared to PHM and normal trophoblasts indicates increased apoptosis and uncontrolled trophoblastic proliferation. Construction of TMA in duplicates using cores of 3 mm diameter can overcome tissue heterogeneity of complex lesions.

To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC).
Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020.
Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC.
Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC.

UNASSIGNED: Complete hydatidiform mole affects women in their reproductive age. About 15-20% develops persistent molar gestational trophoblastic neoplasia (GTN), which is linked with delayed (beyond 56 days) normalization of serum βHCG after surgical evacuation.
UNASSIGNED: The objective of the article is to shorten the duration of normalization time of βHCG with single-dose methotrexate injection in women with high risk complete hydatidiform mole (CHM) after suction evacuation.
UNASSIGNED: Total 76 women with CHM were randomized into intervention and control groups. In the intervention arm (n = 34) women received single dose 100 mg intramuscular methotrexate injection post evacuation and the control group (n = 42) had standard care. Surveillance was done in both groups at two weeks intervals for next six months and duration of normalization of βHCG level was recorded.
UNASSIGNED: Total 94.7% women completed follow-up. Mean of normalization time was significantly lower in the intervention group compared to controls (9.7 weeks versus 14.7 week; P < 0.01). Time to event curve showed significantly earlier cumulative normalization time for the intervention group.
UNASSIGNED: Single-dose 100 mg methotrexate injection is a low-cost, simple intervention to help one out of three women with CHM with high-risk features to achieve normalization of βHCG within 56 days. This might be helpful for people in resource-poor countries where adherence to prolonged surveillance is poor.

To assess whether the incidence and aggressiveness of molar pregnancy (MP) and postmolar gestational trophoblastic neoplasia (GTN) changed during the COVID-19 pandemic.
Observational study with two separate designs: retrospective multicentre cohort of patients with MP/postmolar GTN and a cross-sectional analysis, with application of a questionnaire.
Six Brazilian Reference Centres on gestational trophoblastic disease.
2662 patients with MP/postmolar GTN treated from March-December/2015-2020 were retrospectively evaluated and 528 of these patients answered a questionnaire.
Longitudinal retrospective multicentre study of patients diagnosed with MP/ postmolar GTN at presentation and a cross-sectional analysis, with application of a questionnaire, exclusive to patients treated during the period of study, to assess living and health conditions during the COVID-19 pandemic compared with previous years.
The incidence of MP/postmolar GTN.
Compared with the last 5 pre-pandemic years, MP/postmolar GTN incidence remained stable during 2020 (COVID-19 pandemic). Multivariable logistic regression, adjusted for the patient age, showed that during 2020, presentation with MP was more likely to be >10 weeks of gestation (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.90-3.29, P < 0.001), have a pre-evacuation hCG level ≥100 000 iu/l (aOR 1.77, 95% CI 1.38-2.28, P < 0.001) and time to the initiation of chemotherapy ≥7 months (aOR 1.86, 95% CI 1.01-3.43, P = 0.047) when compared with 2015-2019.
Although the incidence of MP/postmolar GTN remained stable during the COVID-19 pandemic in Brazil, the pandemic was associated with greater gestational age at MP diagnosis and more protracted delays in initiation of chemotherapy for postmolar GTN.

This study aims to estimate the population-based incidence of gestational trophoblastic diseases (GTDs) and to identify the characteristics of gestational trophoblastic neoplasia (GTN) in Japan.
The annual number of GTD and live births from 1974 to 2018 were used to estimate the incidence of GTD. The data of 1,574 GTN cases from 1999 to 2018 were analyzed to identify the characteristics of low-risk GTN, high-risk GTN, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT).
The incidence of hydatidiform mole was 2.02 per 1,000 live births on average which decreased from 1974 to 2008 and increased from 2009 to 2018. The incidence of low-risk GTN, high-risk GTN, PSTT, and ETT was 15.3, 3.5, 0.3, and 0.07 per 100,000 live births, respectively. The estimated incidence of post-molar GTN was 9.8% of molar patients. High-risk GTN was diagnosed more pathologically, had more various kinds of antecedent pregnancies, and had longer intervals after the antecedent pregnancy compared to low-risk GTN. Furthermore, 8.2% of high-risk GTN occurred after the subsequent non-molar pregnancy of hydatidiform mole. The cumulative percentage of developing high-risk GTN after hydatidiform mole reached 89.3% at the 60th month.
The incidence of hydatidiform mole, low-risk GTN, high-risk GTN was 2.02 per 1,000 live births, 15.3 per 100,000 live births, and 3.5 per 100,000 live births, respectively. High-risk GTN was diagnosed more pathologically and later after the antecedent pregnancy than low-risk GTN. Following molar patients for five years is needed to improve the mortality of malignant GTN.

This study aimed to determine whether or not there was a relationship between complete hydatidiform mole (CHM) and serum Vitamin D level by comparing CHM patients with two control groups and to determine whether or not Vitamin D deficiency is a risk factor for CHM.
This prospective study included 30 patients diagnosed with CHM (case group), 30 patients in the first trimester of a healthy pregnancy (control group), and 30 healthy non-pregnant subjects (control group). A record was made of serum 25-hydroxyvitamin D (25-OH D vitamin) levels, age, body mass index (BMI), gravida, parity, and the number of abortus. The serum 25-OH D vitamin levels were examined in each group and compared between groups.
The 25-OH D vitamin level of all the patients in the study was determined as 11.16±8.64 ng/mL. No significant difference was determined between the groups in respect of 25 OH-D vitamin levels. When comparisons were made between the four subgroups according to the 25-OH-D level, no significant difference was determined between the CHM and control groups. When the patients were separated as obese and non-obese groups, no significant difference was determined between the groups.
Severe deficiency, deficiency, or insufficient levels of serum Vitamin D are not thought to be risk factors for CHM patients.

The current ecological study aims to explore the association between dietary factors and hydatidiform mole (HM) incidence in Japan and China. HM incidence in Japan gradually declined from 1970s to 1990s, while the dietary structure also changed during the same period, mainly characterized by a decrease in the consumption of cereals and an increase in the consumption of meat, eggs, and dairy products. In China, HM incidence varied by regions, and it positively correlated with the per capita intake of rice, fish and shrimp, and animal fat, as well as the proportion of GDP of primary industry; and negatively correlated with the per capita intake of wheat flour, starch and sugar, protein, and iron, and the proportion of protein in the caloric nutrients and the proportion of nonagricultural population. In partial analysis, the correlations of HM incidence with rice, fish and shrimp, iron, and the proportion of protein in caloric nutrients remained significant. Meanwhile, alcoholic beverage consumption and the proportion of empty calories in caloric food were also found to be positively correlated with HM incidence, while phosphorus consumption was negatively correlated. Our results suggested that HM incidence could be influenced by dietary factors.

Gestational trophoblastic diseases (GTDs) may follow any form of pregnancy or a pregnancy loss. Early detection of GTDs is important, as some benign forms of the disease may progress into a chemoresistant and metastatic disease. This study aimed at determining the frequency of GTDs among women experiencing first trimester pregnancy loss and the associated patients\' characteristics.
This was a cross-sectional study that included 200 conveniently sampled women who experienced first trimester pregnancy loss from January to December 2019 at a Regional Referral Hospital in central Tanzania. The specimen obtained from products of conception were collected, formalin-fixed and paraffin-embedded and submitted for histopathological evaluation, for which haematoxylin and eosin stain was used. Data were analysed using SPSS version 23.0. The χ2 test was used to determine the association between categorical variables. p-Values ˂0.05 were considered statistically significant.
Among 200 study participants, the overall frequency of GTDs was 42 (21%). Among those with GTDs, the most common histopathological diagnosis was partial hydatidiform mole (18 [42.9%]), followed by complete hydatidiform mole (17 [40.5%]) and choriocarcinoma (7 [16.5%]). In the studied participants, only increased human chorionic gonadotropin hormone levels were found to be statistically significantly associated with GTDs (p=0.000).
Results from this study suggest that routine histopathological evaluation of the products of conception is recommended in order to allow early detection of GTDs, including choriocarcinoma, which usually carries a poor prognosis. The histopathological reporting of choriocarcinoma among first trimester products of conception from Tanzania is novel.