Effects and safety of COVID-19 vaccination on assisted reproductive technology and pregnancy: A comprehensive review and joint statements of the KSRM, the KSRI, and the KOSAR / 대한생식의학회지

Humanity is in the midst of the coronavirus disease 2019 (COVID-19) pandemic, and vaccines—including mRNA vaccines—have been developed at an unprecedented speed. It is necessary to develop guidelines for vaccination for people undergoing treatment with assisted reproductive technology (ART) and for pregnancy-related situations based on the extant laboratory and clinical data. COVID-19 vaccines do not appear to adversely affect gametes, embryos, or implantation; therefore, active vaccination is recommended for women or men who are preparing for ART. The use of intravenous immunoglobulin G (IVIG) for the treatment of immune-related infertility is unlikely to impact the effectiveness of the vaccines, so COVID-19 vaccines can be administered around ART cycles in which IVIG is scheduled. Pregnant women have been proven to be at risk of severe maternal and neonatal complications from COVID-19. It does not appear that COVID-19 vaccines harm pregnant women or fetuses; instead, they have been observed to deliver antibodies against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) to the fetus. Accordingly, it is recommended that pregnant women receive COVID-19 vaccination. There is no rationale for adverse effects, or clinical cases of adverse reactions, in mothers or neonates after COVID-19 vaccination in lactating women. Instead, antibodies to SARS-CoV-2 can be delivered through breast milk. Therefore, breastfeeding mothers should consider vaccination. In summary, active administration of COVID-19 vaccines will help ensure the safe implementation of ART, pregnancy, and breastfeeding.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology / 부인종양

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts:• Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia.• Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method.• The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years.• Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology / 부인종양

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

Bilateral salpingectomy to reduce the risk of ovarian/fallopian/peritoneal cancer in women at average risk: a position statement of the Korean Society of Obstetrics and Gynecology (KSOG)

Based on the current understanding of a preventive effect of bilateral salpingectomy on ovarian/fallopian/peritoneal cancers, the Korean Society of Obstetrics and Gynecology, Korean Society of Gynecologic Endocrinology, Korean Society of Gynecologic Oncology, Korean Society of Maternal Fetal Medicine, and Korean Society for Reproductive Medicine support the following recommendations:• Women scheduled for hysterectomy for benign gynecologic disease should be informed that bilateral salpingectomy reduces the risk of ovarian/fallopian/peritoneal cancer, and they should be counseled regarding this procedure at the time of hysterectomy.• Although salpingectomy is generally considered as a safe procedure in terms of preserving ovarian reserve, there is a lack of evidences representing its long-term outcomes. Therefore, patients should be informed about the minimal potential of this procedure for decreasing ovarian reserve.• Prophylactic salpingectomy during vaginal hysterectomy is favorable in terms of prevention of ovarian/fallopian/peritoneal cancer, although operation-related complications minimally increase with this procedure, compared to the complications associated with vaginal hysterectomy alone. Conversion to open or laparoscopic approach from vaginal approach to perform prophylactic salpingectomy is not recommended.• Women who desire permanent sterilization at the time of cesarean delivery could be counseled for prophylactic salpingectomy before surgery on an individual basis.

Erratum: Correction of the name of society

The name of society was published incorrectly.

Endometrial adenocarcinoma in a 13-year-old girl

Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature.

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.

A case of 17 alpha-hydroxylase deficiency / 대한생식의학회지

17alpha-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In 17alpha-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with 17alpha-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with 17alpha-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with 17alpha-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

Surgical impact on serum anti-Mullerian hormone in women with benign ovarian cyst: A prospective study

OBJECTIVE: The aim of this study was to evaluate the surgical impact of benign ovarian mass on ovarian reserve as measured by serum follicle stimulating hormone (FSH), estradiol (E2) and anti-Mullerian hormone (AMH) levels, antral follicle count (AFC) and ovarian volumes. In addition, the differences in ovarian reserve impairment between endometrioma cystectomy and non-endometrioma cystectomy were investigated. METHODS: In this prospective study, 22 patients of reproductive age (range, 18.35 years) with benign ovarian masses were enrolled to undergo laparoscopic cystectomy. Of whom 12 had endometriomas and 10 had non-endometriomas. On early follicular phase (day 3) of the cycle preceding the operation and three months after the laparoscopic cystectomy, serum levels of FSH, E2 and AMH, AFC and ovarian volumes were measured in all patients. Data were analyzed with Mann-Whitney U-test and Wilcoxon rank test using SPSS ver. 12.0 for statistic analysis. RESULTS: Median level of serum AMH was significantly decreased from 5.48 ng/mL (interquartile range [IQR], 2.80-7.47) before cystectomy to 2.56 ng/mL (IQR, 1.74-4.32) 3 months postoperation (P<0.05). On the other hand, no significant differences in FSH, E2, AFC and ovarian volumes were found between the preoperative and three months postoperative levels. In a subgroup analysis of the pathologic type of the ovarian cyst, postoperative serum AMH levels were significantly decreased in the endometrioma group, but not in the non-endometrioma group. CONCLUSION: Serum AMH levels were significantly decreased after laparoscopic cystectomy without any changes of other ovarian reserve tests.

Arteriovenous malformation in uterine cervix during pregnancy

As the development of Doppler ultrasonography, many cases of uterine arteriovenous malformation (AVM) have beed diagnosed. But there is no case of cervical AVM in pregnant uterus. We present a 33-year-old pregnant woman who was diagnosed with AVM of the uterine cervix during the midtrimester. Color Doppler sonography and magnetic resonance image were used for diagnosis. We performed Cesarean section because of the risk of massive bleeding from the cervical AVM at 34 weeks' gestation. This is the first case of cervical AVM during pregnancy with a successful outcome and an uneventful postpartum course.

A Case of Successful Conservative Management for Spontaneous Hemoperitoneum in the 3rd Trimester Pregnancy / 대한주산의학회잡지

At early stage of pregnancy, hemoperitoneum often occurs in heterotopic ectopic pregnancy or bleeding of hyperstimulated ovary and can be managed easily by laparoscopic surgery while maintaining pregnancy. But in the 3rd trimester pregnancy, surgical management without delivery is very difficult and preterm birth is inevitable because of life-threatening complications not only for mother but fetus. We present a woman with 31 weeks and 3 days' gestation and spontaneous hemoperitoneum that was treated by conservative management without preterm delivery successfully. A review of the literature was undertaken.

Pulmonary and retroperitoneal benign metastasizing leiomyoma / 대한생식의학회지

Benign metastasizing leiomyoma (BML) is a rare disease, which usually occurs in women with a history of a prior hysterectomy or myomectomy for benign uterine leiomyoma, and has the potential to metastasize to distant sites, such as the lung, lymph nodes, muscular tissue, heart, or retroperitoneum. These lesions are slow-growing, asymptomatic, and usually found incidentally. The prognosis of BML is also excellent. However, there has been debate on the origin and the correct classification of BML, and there are no guidelines for the treatment of BML. We report here on a rare case of BML in both the retroperitoneal cavity and lung in a 48-year-old woman with a history of hysterectomy due to histologically benign uterine leiomyoma. The patient underwent retroperitoneal mass excision and bilateral salpingo-oophorectomy, and then wedge biopsy of two pulmonary nodules was performed additionally 9 days later. Until now, there has been no sign of recurrence and the patient remains asymptomatic. To our knowledge, pulmonary BML is rare and the co-existence of the retroperitoneal metastases after previous hysterectomy is even rarer.

Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome / 대한생식의학회지

OBJECTIVE: This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). METHODS: We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, menstrual status from 117 women with PCOS. Statistical analysis was performed with chi square and t-test, p-value<0.05 was considered as statistically significant. And receiver operating characteristic curve was used to find predictable clinical factors for endometrial disease and to decide the cuff off values. RESULTS: In 117 women with PCOS, endometrial histologic profiles are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%), 6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were significantly related with endometrial disease, p=0.013 and p=0.001, respectively. At the cut off level of 25.5 years in age, sensitivity and specificity predicting for endometrial disease were 70.4% and 55.6%, respectively (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity and specificity were 77.8% and 56.7%, respectively (p=0.000). CONCLUSION: In women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4% and 1.7%. The age and endometrial thickness may be used as clinical determining factors for endometrial biopsy.

Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome / 대한생식의학회지

OBJECTIVE: This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). METHODS: We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, menstrual status from 117 women with PCOS. Statistical analysis was performed with chi square and t-test, p-value<0.05 was considered as statistically significant. And receiver operating characteristic curve was used to find predictable clinical factors for endometrial disease and to decide the cuff off values. RESULTS: In 117 women with PCOS, endometrial histologic profiles are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%), 6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were significantly related with endometrial disease, p=0.013 and p=0.001, respectively. At the cut off level of 25.5 years in age, sensitivity and specificity predicting for endometrial disease were 70.4% and 55.6%, respectively (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity and specificity were 77.8% and 56.7%, respectively (p=0.000). CONCLUSION: In women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4% and 1.7%. The age and endometrial thickness may be used as clinical determining factors for endometrial biopsy.

Diagnostic approach of amenorrhea / 대한산부인과학회지

A complete interaction in the hypothalamic-pituitary-ovary-uterus (H-P-O-U) axis must take place in order for normal menstruation occurs. If any of the components in the H-P-O-U axis are nonfunctional, amenorrhea could occur. The prevalence of amenorrhea not due to pregnancy or lactation is approximately 3% to 4% in reproductive women. Because there are many causes of amenorrhea, the clinicians should be concerned with array of potential diseases and disorders involving unfamiliar organ systems, some carrying morbid and even lethal consequences for the patients. To explore the causes of amenorrhea, thorough evaluation of H-P-O-U axis and endocrinologic profiles are needed. The etiologic diagnosis is almost always possible with proceeding step by step approaches.

Repetitive Pregnancy Loss in inv(22)(p13q12) Carrier

Pericentric inversion is not rare in humans and is usually benign. However, pericentric inversion can lead to production of an unbalanced recombinant and might be a cause of repetitive pregnancy loss. Pericentric inversion of chromosome 22 is rare and only a few cases have been reported. We report a case of inv(22)(p13q12) carrier who had history of repetitive pregnancy loss including three spontaneous abortions and one fetal hydrops in which the chromosomal complement was rec(22)dup(22q) inv(22)(p13q12)mat. The maternal inv(22) and fetal rec(22) were confirmed by fluorescence in situ hybridization using region-specific probes (TUPLE1 on 22q11.2 and ARSA on 22q13). Because the identification of inv(22) or rec(22) in conventional karyotyping might be easily overlooked, great attention and additional molecular tests are required for accurate diagnosis of inv(22) and rec(22).

Live twin tubal ectopic pregnancy after ovulation induction / 대한산부인과학회지

Twin tubal ectopic pregnancy is rare. Especially the live twin tubal ectopic pregnancy is extremely rare, just 10 cases have been reported until now. There were 9 cases of live twin tubal pregnancy after spontaneous conception and one case after IVF cycle. This is the first report of live twin tubal ectopic pregnancy after ovulation induction with clomiphene citrate. A 31-year-old woman, nulligravida complained of primary infertility and irregular menstruation. After ovulation induction with clomiphen citrate, beta-hCG was 1566 mIU/mL on missed period of 5 weeks 4 days. On 6(+1) weeks, beta-hCG was elevated to 3446 mIU/mL and transvaginal ultrasound revealed two separated gestational sacs, each containing yolk sac in the left tube. The variable dose of methotrexate therapy was tried using 1 mg/kg of methotrexate and 0.1 mg/kg of leukovorin. These were injected alternatively for 8 days. On 7(+3) weeks, beta-hCG was elevated to 8,029 mIU/mL and transvaginal ultrasound revealed two fetal poles with heart beat in each gestational sacs. Laparoscopic salpingectomy was performed. The diagnosis was confirmed by the operative finding and also in the pathologic report. It is needed that careful ultrasonographic examination especially in the case of ovulation induction or IVF-ET. Methotrexate treatment in twin tubal pregnancy was usually failed. There was only one successful report by the direct injection of methotrexate to the fallopian tube combined with single intramuscular injection. Further research for dosage or route of administration will be needed.

High fever, coronary artery spasm and convulsion associated with prostaglandin E2 in atonic uterine bleeding / 대한산부인과학회지

Postpartum hemorrhage is a serious condition related with maternal morbidity and mortality. Prior to surgical treatment, oxytocin and prostaglandin analogs administration are common. Pyrexia after prostaglandin E1 was well known, but PG E2 has been shown to have a few complication even though coronary arterial spasm was rarely reported. The 38-year old woman who delivered 3rd baby by Cesarean section was developed the atonic uterine bleeding. During the treatment with high dose sulprostone (PG E2), she complained the anterior chest pain, her body temperature was elevated to 41.2 degrees C, and then convulsion with stuporous mentality was developed. EKG revealed inverted T wave in II. III, aVF lead, and CK-MB, troponin I was elevated. The laboratory test revealed elevated SGOT/SGPT, myoglobin, and metabolic acidosis. But CSF study, blood culture, direct/indirect Coomb's test, brain CT, and echocardiography were all negative. After supportive care, she came to be alert after 10 hours, body temperature was returned to normal after 22 hours, and the laboratory tests were eventually returned to normal within 6 days. She was discharged from the hospital without any complication. We postulate that high dose PG E2 resulted in high fever, coronary artery spasm, and convulsion