Contraception in the COVID-19 pandemic: recommendations from the Korean society of contraception and reproductive health

Coronavirus disease 2019 (COVID-19) is associated with a systemic inflammatory response that activates coagulation in symptomatic patients. In addition, a rare form of thrombosis has been reported in people who received the COVID-19 vaccine, most of whom were women younger than 50 years of age. Considering that hormonal contraceptive methods widely used by women of childbearing age increase the risk of thrombosis, the development of guidelines for the use of hormonal contraceptives in the era of the COVID-19 pandemic is necessary. In this context, the Korean Society of Contraception and Reproductive Health provides guidelines for issues regarding contraception and reproductive health during the pandemic.

Delayed diagnosis of gestational diabetes mellitus and perinatal outcomes in women with large for gestational age fetuses during the third trimester

Objective@#We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. @*Methods@#A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. @*Results@#Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. @*Conclusion@#Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

Metachronous Sporadic Sextuple Primary Malignancies Including Bilateral Breast Cancers / 한국유방암학회지

Multiple primary malignancies are defined as the presence of more than one malignant neoplasm with a distinct histology occurring at different sites in the same individual. They are classified as synchronous or metachronous according to the diagnostic time interval of different malignancies. Diagnosis of multiple primary malignancies should avoid misclassification from multifocal/multicentric tumors or recurrent/metastatic lesions.In multiple primary malignancies, with increase in the number of primary tumors, the frequency rapidly decreases. Here, we report an exceptionally rare case of a woman who was diagnosed with metachronous sporadic sextuple primary malignancies including bilateral breast cancers (gastric cancer, ovarian Sertoli-Leydig cell tumor, left breast cancer, thyroid cancer, right breast cancer, and rectal neuroendocrine tumor). The sextuple primary malignancies in this case involved 5 different organs: the stomach, ovary, thyroid, rectum, and bilateral breasts. Further studies are needed to elucidate the current epidemiologic status of patients with multiple primary malignancies.

Delayed diagnosis of gestational diabetes mellitus and perinatal outcomes in women with large for gestational age fetuses during the third trimester

Objective@#We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. @*Methods@#A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. @*Results@#Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. @*Conclusion@#Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

Metachronous Sporadic Sextuple Primary Malignancies Including Bilateral Breast Cancers / 한국유방암학회지

Multiple primary malignancies are defined as the presence of more than one malignant neoplasm with a distinct histology occurring at different sites in the same individual. They are classified as synchronous or metachronous according to the diagnostic time interval of different malignancies. Diagnosis of multiple primary malignancies should avoid misclassification from multifocal/multicentric tumors or recurrent/metastatic lesions.In multiple primary malignancies, with increase in the number of primary tumors, the frequency rapidly decreases. Here, we report an exceptionally rare case of a woman who was diagnosed with metachronous sporadic sextuple primary malignancies including bilateral breast cancers (gastric cancer, ovarian Sertoli-Leydig cell tumor, left breast cancer, thyroid cancer, right breast cancer, and rectal neuroendocrine tumor). The sextuple primary malignancies in this case involved 5 different organs: the stomach, ovary, thyroid, rectum, and bilateral breasts. Further studies are needed to elucidate the current epidemiologic status of patients with multiple primary malignancies.

Menopausal hormone therapy in the cancer survivors

Due to advances in the treatment and diagnosis of cancer, many women survive long after treatment, and therefore express concerns about the impact of estrogen deficiency on their quality of life. Cancer treatment can induce menopause through surgical removal of the ovaries, chemotherapy, or radiation. Women who undergo induced menopause usually experience more sudden and severe menopausal symptoms, including vasomotor symptoms, psychological symptoms, genitourinary symptoms, cardiovascular disease, and osteoporosis. Menopausal hormone therapy (MHT) is especially important in women younger than 40. In this review, we consider the role of MHT after the diagnosis of breast, gynecologic, colorectal, stomach, liver, lung, and hematologic cancers. MHT is advantageous in endometrial cancer type I, cervical squamous cell carcinoma, colorectal cancer, hepatocellular carcinoma, and hematologic malignancies. However, MHT is not recommended for use in breast cancer, endometrial stromal sarcoma, hormone receptor–positive gastric cancer, and lung cancer survivors because it is linked to an increased risk of cancer recurrence. Depending on the type of cancer, clinicians should recommend that cancer survivors receive appropriate MHT in order to reduce vasomotor symptoms and to benefit from its positive effects on the cardiovascular and skeletal systems.

Menopausal hormone therapy in the cancer survivors

Due to advances in the treatment and diagnosis of cancer, many women survive long after treatment, and therefore express concerns about the impact of estrogen deficiency on their quality of life. Cancer treatment can induce menopause through surgical removal of the ovaries, chemotherapy, or radiation. Women who undergo induced menopause usually experience more sudden and severe menopausal symptoms, including vasomotor symptoms, psychological symptoms, genitourinary symptoms, cardiovascular disease, and osteoporosis. Menopausal hormone therapy (MHT) is especially important in women younger than 40. In this review, we consider the role of MHT after the diagnosis of breast, gynecologic, colorectal, stomach, liver, lung, and hematologic cancers. MHT is advantageous in endometrial cancer type I, cervical squamous cell carcinoma, colorectal cancer, hepatocellular carcinoma, and hematologic malignancies. However, MHT is not recommended for use in breast cancer, endometrial stromal sarcoma, hormone receptor–positive gastric cancer, and lung cancer survivors because it is linked to an increased risk of cancer recurrence. Depending on the type of cancer, clinicians should recommend that cancer survivors receive appropriate MHT in order to reduce vasomotor symptoms and to benefit from its positive effects on the cardiovascular and skeletal systems.

Effectiveness and safety of sublingual misoprostol in medical treatment of the 1st trimester miscarriage: experience of off-label use in Korea

OBJECTIVE: This study was conducted to determine the effectiveness and safety of medical treatment with sublingual misoprostol (MS) in the 1st trimester miscarriage under the approval by Health Insurance Review and Assessment Service (HIRA) for off-label usage by the single medical center in Korea. METHODS: A retrospective cohort study was performed in one institution between April 2013 and June 2016. Ninety-one patients diagnosed with miscarriage before 14 weeks of gestation and wanted to try medical treatment were included. A detailed ultrasound scan was performed to confirm the diagnosis. Patients took 600 microgram (mcg) of MS sublingually at initial dose, and repeated the same dose 4–6 hours apart. Successful medical abortion was defined as spontaneous expulsion of gestational products (including gestational sac, embryo, fetus, and placenta). If gestational products were not expelled, surgical evacuation was performed at least 24 hours later from the initial dose. Information about side effects was obtained by medical records. RESULTS: About two-thirds of patients had a successful outcome. The median interval time from pill to expulsion was 18 hours in the successful medical treatment group. There was no serious systemic side effect or massive vaginal bleeding. Presence or absence of vaginal spotting before diagnosis of miscarriage, uterine leiomyomas, subchorionic hematoma, or distorted shape of gestational sac on ultrasound scan were not statistically different between the two groups. CONCLUSION: Medical treatment with sublingual MS can be a proper option for the 1st trimester miscarriage, especially for the patient who want to avoid surgical procedure. We can reduce the unnecessary sedation or surgical intervention in the patients with the 1st trimester miscarriage.

Serum visfatin levels in non-obese women with polycystic ovary syndrome and matched controls

OBJECTIVE: The purpose of the current study was to compare the circulating levels of visfatin between women with polycystic ovary syndrome (PCOS) and those without PCOS and to assess the correlations between visfatin levels and various parameters. METHODS: This case-control study recruited 74 PCOS patients and 74 age- and body mass index (BMI)-matched controls. Serum visfatin levels were evaluated using the enzyme-linked immunosorbent assay. Women with PCOS were divided into 2 subgroups based on the presence of clinical or biochemical hyperandrogenism. The possible differences in serum visfatin levels between the hyperandrogenic and non-hyperandrogenic groups were also assessed. RESULTS: Visfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients had significantly higher mean serum visfatin levels than those in non-hyperandrogenic patients (3.87 ng/mL; 95% confidence intervals [CIs], 3.09–4.85 in hyperandrogenic group vs. 2.69 ng/mL; 95% CIs, 2.06–3.52 in non-hyperandrogenic group; P=0.038). In women with PCOS, visfatin levels positively correlated with BMI (r=0.23; P=0.047) and the log free androgen index (FAI) (r=0.27; P=0.021) and negatively correlated with high-density lipoprotein (HDL) cholesterol levels (r=−0.37; P=0.025). Except for HDL cholesterol levels, these correlations were also observed in controls. CONCLUSION: Visfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients showed significantly higher serum visfatin levels than those of non-hyperandrogenic patients, and visfatin had a positive linear correlation with FAI in both PCOS patients and controls.

Erratum: Correction of Acknowledgements

The Acknowledgements was published incorrectly. The authors apologize for any inconvenience that it may have caused.

The clinical significance of D-dimer concentrations in patients with gestational hypertensive disorders according to the severity

OBJECTIVE: Pregnancy is a major risk factor of thromboembolism, and the patients with preeclampsia (PE) are known to have higher risk of thromboembolic complications than normal pregnant women. D-dimer is a well-established laboratory marker for the screening of venous thromboembolism (VTE), but the concentrations of d-dimer tend to increase physiologically in pregnant women throughout the gestational age. We performed this study to evaluate the clinical significance of d-dimer concentrations in patients with gestational hypertensive disorders (GHD) according to the severity. METHODS: Retrospective cohort study was performed in one institution. Singleton pregnant women with GHD were enrolled, and their antepartum concentrations of d-dimer were measured as a part of routine evaluation for patients suspected with PE. Patients with multiple gestations, rheumatic diseases, autoimmune diseases, or suspected VTE were excluded. A categorization of severity about PE was based on the general criteria. RESULTS: In 73.3% of study population, their d-dimer concentrations exceeded the normal range (>0.55 mg/L). A significantly greater proportion of pregnant women had excessive concentrations of d-dimer in the severe GHD than in the non-severe GHD (89.8% vs. 53.7%; P<0.01). Patients with severe GHD had significantly higher median concentrations of d-dimer than those with non-severe GHD (median [range], 2.00 mg/L [0.11 to 7.49] vs. 0.71 mg/L [0.09 to 5.39]; P<0.01) although their earlier gestational ages of sampling. CONCLUSION: Maternal concentrations of d-dimer were significantly elevated in patients with severe features than those without severe features among those with GHD. Some pregnant women with GHD can have markedly elevated concentrations of d-dimer without any evidence of current VTE.

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Recurrent Pregnancy Loss: a Case-Control Study

The balance between coagulation and fibrinolysis is an essential part in early pregnancy. Mutations in methylenetetrahydrofolate reductase (MTHFR) gene lead to decreased activity of the enzyme and hyperhomocysteinemia, which then induces platelet aggregation by promoting endothelial oxidative damage, possibly resulting in adverse effect on maintenance of pregnancy. We investigated the role of MTHFR single nucleotide polymorphisms (SNPs), C677T and A1298C, in Korean patients with recurrent pregnancy loss (RPL). We conducted a prospective case-control study in the Korean population. Subjects included 302 women with 2 or more consecutive, unexplained, spontaneous miscarriages before 20 weeks of gestation and 315 control women without a history of recurrent miscarriages. The genotyping for C677T and A1298C polymorphisms was performed using the TaqMan assay. Continuous variables were compared using Student's t-test, and χ² test was used to evaluate differences in the genotype distributions between the RPL and the controls. The genotype distribution of both polymorphisms in the RPL group did not differ from those of the controls. For further analysis, if RPL patients were divided according to the numbers of pregnancy losses (≥ 2 and ≥ 3) neither group was significantly different compared with controls. MTHFR gene C677T and A1298C polymorphisms are not associated with idiopathic RPL in Korean women, suggesting that those may not be susceptible allelic variants or be deficient to cause RPL.

Gestational Age-specific Cut-off Values Are Needed for Diagnosis of Subclinical Hypothyroidism in Early Pregnancy

During the first trimester of pregnancy, thyroid-stimulating hormone (TSH) >2.5 mIU/L has been suggested as the universal criterion for subclinical hypothyroidism. However, TSH levels change continuously during pregnancy, even in the first trimester. Therefore the use of a fixed cut-off value for TSH may result in a different diagnosis rate of subclinical hypothyroidism according to gestational age. The objective of this study was to obtain the normal reference range of TSH during the first trimester in Korean gravida and to determine the diagnosis rate of subclinical hypothyroidism using the fixed cut-off value (TSH >2.5 mIU/L). The study population consisted of pregnant women who were measured for TSH during the first trimester of pregnancy (n=492) and nonpregnant women (n=984). Median concentration of TSH in pregnant women was lower than in non-pregnant women. There was a continuous decrease of median TSH concentration during the first trimester of pregnancy (median TSH concentration: 1.82 mIU/L for 3+0 to 6+6 weeks; 1.53 mIU/L for 7+0 to 7+6 weeks; and 1.05 mIU/L for 8+0 to 13+6 weeks). Using the fixed cut-off value of TSH >2.5 mIU/L, the diagnosis rate of subclinical hypothyroidism decreased significantly according to the gestational age (GA) at TSH (25% in 3+0 to 6+6 weeks, 13% in 7+0 to 7+6 weeks, and 9% for 8+0 to 13+6 weeks, P<0.001), whereas the diagnosis rate was 5% in all GA with the use of a GA-specific cut-off value (P=0.995). Therefore, GA-specific criteria might be more appropriate for the diagnosis of subclinical hypothyroidism.

Vitamin D deficiency in women with polycystic ovary syndrome / 대한생식의학회지

OBJECTIVE: To investigate: the prevalence of vitamin D deficiency in Korean women with polycystic ovary syndrome (PCOS), and the relationship between vitamin D status and clinical or metabolic features in this group. METHODS: We recruited 38 women with PCOS using the Rotterdam criteria. A total of 109 premenopausal control women were matched with patients based on age and body mass index. Serum 25-hydroxy vitamin D concentrations less than 20 ng/mL were classified as frank vitamin D deficiency. Since vitamin D may play a significant role in metabolic disturbances in women with PCOS, correlations between clinical or metabolic parameters and vitamin D status were analyzed separately in patients and controls. RESULTS: Women with PCOS showed no differences in the level of 25-hydroxy vitamin D (19.6+/-6.6 ng/mL in patients vs. 20.1+/-7.4 ng/mL in controls, respectively, p=0.696) or prevalence of vitamin D deficiency (57.9% in patients vs. 56.5% in controls, respectively, p=0.880). In addition, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles in either PCOS patients or controls. CONCLUSION: Our study found no differences in the absolute level of serum vitamin D between PCOS patients and matched controls. Prevalence of vitamin D deficiency was equally common among both patients and controls. Additionally, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles, suggesting that the role of vitamin D in the pathogenesis of PCOS is not yet clear.

A case of vulvar hematoma with rupture of pseudoaneurysm of pudendal artery

Vulvar hematomas are uncommon outside of the obstetric population and may be the result of trauma to the perineum. Vulvar hematomas most often present with low abdominal pain and urologic and neurologic symptoms. The vulva has rich vascularization that is supplied by the pudendal artery, a branch of the anterior division of the internal iliac artery. We describe a rare case of a 15-cm-sized vulvar hematoma with the suggested rupture of a pseudoaneurysm of the left pudendal artery without trauma injury. A 14-year-old girl presented with sudden pain and swelling in her left labium and was successfully treated with selective arterial embolization and surgical evacuation. We provide a literature review and discuss patient treatment and management strategies.

Uterine infarction in a patient with uterine adenomyosis following biochemical pregnancy / 대한생식의학회지

Adenomyosis is a common gynecological disorder characterized by the presence of endometrial glands and stroma deep within the myometrium associated with myometrial hypertrophy and hyperplasia. Focal uterine infarction after IVF-ET in a patient with adenomyosis following biochemical pregnancy has not been previously reported, although it occurs after uterine artery embolization in order to control symptoms caused by fibroids or adenomyosis. We report a case of a nulliparous woman who had uterine adenomyosis presenting with fever, pelvic pain and biochemical abortion after undergoing an IVF-ET procedure and the detection of a slightly elevated serum hCG. Focal uterine infarction was suspected after a pelvic magnetic resonance imaging demonstrated preserved myometrium between the endometrial cavity and inner margin of the necrotic myometrium. This case demonstrates that focal uterine infarction should be considered in the differential diagnosis of acute abdominal pain, vaginal bleeding and infectious signs in women experiencing biochemical abortion after an IVF-ET procedure.

Effects of insulin-sensitizing agents and insulin resistance in women with polycystic ovary syndrome / 대한생식의학회지

OBJECTIVE: The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. RESULTS: One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. CONCLUSION: Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.

Carotid intima-media thickness in mainly non-obese women with polycystic ovary syndrome and age-matched controls

OBJECTIVE: Metabolic disturbances are well-recognized clinical features of polycystic ovary syndrome (PCOS). Carotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD). CIMT in women with PCOS has been investigated in many studies, but there has been only one report in the Korean population. The aim of the present study was to compare the presence of subclinical atherosclerosis in young untreated Korean women with PCOS and age-matched controls, specifically by measuring their CIMT. METHODS: CIMT was measured by one radiologist in 56 PCOS patients and 56 controls. To compare the CIMT according to PCOS phenotypes, women with PCOS were divided into two subgroups according to the presence of hyperandrogenism. RESULTS: Although PCOS patients were more obese and had higher blood pressure and insulin resistance index than the age-matched controls, the CIMT was not different between the two groups (0.49 +/- 0.09 mm in PCOS patients vs. 0.50 +/- 0.11 mm in controls, respectively, p = 0.562). When the CIMT in the control group was compared with hyperandrogenic and non-hyperandrogenic PCOS groups, also no significant differences were found. CONCLUSION: Despite the significant differences in some vascular risk factors between women with PCOS and controls, PCOS patients did not have a significantly higher CIMT (even in the hyperandrogenic subgroups). Although our study did not show the increased risk of subclinical atherosclerosis in PCOS patients, the role of CIMT continues to be investigated considering the importance of screening and monitoring CVD risk factors in women with PCOS.

A third stage pelvic organ prolapse due to cervical swelling during labor: A case report / 대한산부인과학회지

Pelvic organ prolapse complicating pregnancy is a rare clinical condition and its incidence is one in 10,000~15,000 deliveries. It is associated with multiparity, low socioeconomic status, inadequate perinatal care, maternal malnutrition, previous abdominal surgery, and weakness of pelvic muscular and connective tissue. It can cause cervical dystocia, which leads to cervical laceration, uterine rupture, maternal and fetal death. We experienced a case, first in Korea, of cervical swelling that developed during labor, prolapsed beyond the vaginal introitus and thus obstructed the birth canal. The patient underwent cesarean section and subsequently received MgSO4 topical therapy and resulted in complete resolution. We report this case with a brief review of literature.

Decrease in acceptance of genetic amniocentesis after alteration of social conditions toward pregnancy termination / 대한산부인과학회지

OBJECTIVE: To investigate the effect of alteration of social conditions towards pregnancy termination on the acceptance of genetic amniocentesis. METHODS: Retrospective review of medical records was conducted for women ( 35 years in the 2010 group (5/30, 17%) were less likely to accept genetic amniocentesis than 2009 group (15/30, 50%; P=0.01). Similar results were observed in those who were indicated for genetic amniocentesis. (9/35, 26% vs 19/34, 56%; P=0.02). Acceptance rate of genetic amniocentesis was increased for those who were referred from private clinic, but without statistical significance (15/21, 71% vs 13/14, 93%; P=0.20). CONCLUSION: After strict regulation of pregnancy termination, acceptance rate of genetic amniocentesis was significantly decreased among women who had increased risk for chromosomal abnormalities or neural tube defect at our center. Whereas, there were no significant change in acceptance rate for those who were referred for amniocentesis from private clinic.