Pregnancy and neonatal outcomes after periconceptional exposure to isotretinoin in Koreans

Objective@#Isotretinoin should not be used during pregnancy because of the risk of birth defects. Most pregnant women exposed to isotretinoin choose voluntary pregnancy termination due to concerns about birth defects. However, birth outcome data supporting the termination of pregnancy are lacking. This study aimed to evaluate pregnancy and neonatal outcomes after periconception exposure to isotretinoin. @*Methods@#This was a prospective cohort study. We evaluated pregnancy and neonatal outcomes after exposure to isotretinoin in 151 pregnant women. Among 1,026 callers at the Korean Teratology Information Service from 2001 to 2017 exposed to isotretinoin during the periconception period, 151 pregnant women who received counseling on teratogenic risk after visiting the clinic were included. @*Results@#Among the 151 participants who visited the clinic, only 42 were evaluated using ultrasonography until approximately 20 weeks of gestation. Ultimately, 23 patients were included in the study. The average gestation period during the last exposure to the drug was 2 weeks, and the average daily exposure dose was 12 mg. There were two cases of major birth defects in the exposure group. Spontaneous abortion rates were 17.7% and 8.7% in the exposure and nonexposure groups, respectively (P=0.035). There was no significant difference between the exposure and non-exposure groups in terms of pregnancy and neonatal outcomes. @*Conclusion@#There was no significant difference in pregnancy and neonatal outcomes, including birth defects, between the exposure and non-exposure groups. Further studies with larger sample sizes are required to validate our findings.

The rates of major malformations after gestational exposure to isotretinoin: a systematic review and meta-analysis

Objective@#Isotretinoin is among the most notorious human teratogens, documented originally as causing up to 30% of malformations. This systematic review and meta-analysis aimed to evaluate the rates of major malformation (MM) among isotretinoin-exposed pregnant women over the years through a systematic review and meta-analysis. @*Methods@#Eligible studies were searched and identified using various databases. Single-arm meta-analysis and meta-analysis of odd ratios among controlled studies were performed using Review Manager version 5.3. @*Results@#Ten eligible studies that combined 2,783 isotretinoin-exposed women were included in our study. The rate of MM weighted for the sample size was 15%. Three studies that included an unexposed comparison group were eligible for the meta-analysis. The pooled odds ratio of MM for isotretinoin-exposed women was 3.76. After 2006, the pooled odds ratio of MM for isotretinoin exposure was significantly lower at 1.04. @*Conclusion@#The current rate of MM in isotretinoin-exposed women was substantially lower after 2006.

The rates of major malformations after gestational exposure to isotretinoin: a systematic review and meta-analysis

Objective@#Isotretinoin is among the most notorious human teratogens, documented originally as causing up to 30% of malformations. This systematic review and meta-analysis aimed to evaluate the rates of major malformation (MM) among isotretinoin-exposed pregnant women over the years through a systematic review and meta-analysis. @*Methods@#Eligible studies were searched and identified using various databases. Single-arm meta-analysis and meta-analysis of odd ratios among controlled studies were performed using Review Manager version 5.3. @*Results@#Ten eligible studies that combined 2,783 isotretinoin-exposed women were included in our study. The rate of MM weighted for the sample size was 15%. Three studies that included an unexposed comparison group were eligible for the meta-analysis. The pooled odds ratio of MM for isotretinoin-exposed women was 3.76. After 2006, the pooled odds ratio of MM for isotretinoin exposure was significantly lower at 1.04. @*Conclusion@#The current rate of MM in isotretinoin-exposed women was substantially lower after 2006.

Perioperative Management of Anemia Based on Patient Blood Management / 대한수혈학회지

Perioperative anemia is common during surgery and is an important risk factor for the transfusion of RBC, morbidity and mortality. Blood transfusion has been a common practice for a long time, and has been a traditionally accepted solution to perioperative anemia. However, increasing evidence is now showing that this traditional treatment may actually do more harm than good. Research has shown that transfusion is independently associated with morbidity and mortality. A paradigm shift is currently taking place towards patient-oriented blood management and patient blood management, PBM. PBM consists of 3 pillars: the optimization of the red blood cell mass, reduction of blood loss and bleeding, and optimization of the patients’ physiological tolerance toward anemia. Of the three fillers, perioperative management is mainly included in the second pillar, but integration of these 3 pillars and strategies into perioperative pathways should improve care processes and patient outcome. Bleeding during surgery and efforts to stop it continue, and treatment for bleeding and many hemostatic methods have been developed. In recent decades, minimally invasive surgical techniques have led to a reduction of bleeding, where hemostatic agents, surgical instruments and new techniques have played an important role in the perioperative field of PBM. This paper summarized why PBM is needed, and the strategy during surgery simply and easily. This paper focuses on the surgeons’ role in PBM. The main PBM protocol is not discussed, but rather the paper focuses on selective clinical practice.

Era of Bloodless Surgery: Spotlights on Hemostasic Materials and Techniques / 한양의대학술지

Ever since mankind has had blood, efforts to stop bleeding have never ceased and so numerous methods for hemostasis have been developed. In recent decades, minimally invasive surgical techniques have led patients to less-bleeding surgery but, hemostatic agents, devices and techniques still play an important role in medical side. A number of hemostatic agents and devices have been developed and they can be classified by their mechanism of action. That classification of the coagulants includes mechanisms with physical, caustic, bio-physical, biologic actions. Hemostatic devices are divided into categories such as dressings, glue, clips, electrocoagulations and so on. Based on the concept of minimally invasive surgical procedures, variously developed surgical techniques are divided by the number of ports used and auxiliary instruments. However, there are advantages and disadvantages to each of the hemostatic agents and minimally invasive methods, and the belief in the classical method also prevents the application of new hemostatic methods. The knowledge and understanding of the benefits and costs of these newly developed hemostatic methods will make it easier for medical personnel to manage patient's blood.

Delayed intestinal perforation and vertebral osteomyelitis after high-intensity focused ultrasound treatment for uterine leiomyoma

High-intensity focused ultrasound (HIFU) is a non-invasive uterine fibroid treatment option for patients who want to preserve fertility. However, according to several reports regarding ablation of solid tumors by HIFU, there are rare complications in patients with uterine leiomyomas, and overall data are still insufficient. Here, we report rare and major complications of HIFU, such as delayed intestinal perforation, uterine perforation with recto-uterine fistula, and osteomyelitis 29 days after the HIFU procedure to treat multiple myomas. Thus, we present a very serious case resulting from HIFU treatment of uterine fibroids and a review of the literature.

Innervation in women with uterine myoma and adenomyosis

OBJECTIVE: To determine if neurofilament (NF) is expressed in the endometrium and the lesions of myomas and adenomyosis, and to determine their correlation. METHODS: Histologic sections were prepared from hysterectomies performed on women with adenomyosis (n=21), uterine myoma (n=31), and carcinoma in situ of the uterine cervix. Full-thickness uterine paraffin blocks, which included the endometrium and myometrium histologic sections, were stained immunohistochemically using the antibodies for monoclonal mouse antihuman NF protein. RESULTS: NF-positive cells were found in the endometrium and myometrium in 11 women with myoma and in 7 with adenomyosis, but not in patients with carcinoma in situ of uterine cervix, although the difference was statistically not significant. There was no significant difference between the existence of NF-positive cells and menstrual pain or phases. The NF-positive nerve fibers were in direct contact with the lesions in nine cases (29.0%) of myoma and in five cases (23.8%) of adenomyosis. It was analyzed if there was a statistical significance between the existence of NF positive cells in the endometrium and the expression of NF-positive cells in the uterine myoma/adenomyosis lesions. When NF-positive cell were detected in the myoma lesions, the incidence of NF-positive nerve cells in the eutopic endometrium was significantly high. When NF-positive cell were detected in the basal layer, the incidence of NF-positive nerve cells in the myoma lesions and adenomyosis lesions was significantly high. CONCLUSION: We assume that NF-positive cells in the endometrium and the myoma and adenomyosis lesions might play a role in pathogenesis. Therefore, more studies may be needed on the mechanisms of nerve fiber growth in estrogen-dependent diseases.

Discrepancy between Non-stress Test Result and Umbilical Artery Doppler Study in a Pregnancy Complicated by Diabetes; A Case Report / 대한주산의학회잡지

Pregestational diabetes is a well-known risk factor for perinatal mortality, and regarded as an important cause of stillbirth. Unfortunately, more than half of stillbirths remain unexplained. Nevertheless, there is no consensus regarding the optimal timing and content of antepartum testing in pregnancies complicated by diabetes. A 32-year-old primigravida presented with diabetes diagnosed during pregnancy. Antenatal fetal surveillance tests including nonstress test, biophysical profile, and Doppler waveforms of umbilical arteries were performed twice weekly, beginning at 32 weeks gestation. At 37(+4) weeks' gestation, a discrepancy in the surveillance test results arose when reversed end-diastolic flow in the umbilical arteries was seen, despite a reactive nonstress test. A male baby was delivered by cesarean section. The umbilical arterial pH at delivery was 7.171. Antenatal fetal surveillance in pregnancies complicated by diabetes should include evaluation of Doppler waveforms in the umbilical vessels, regardless of the presence or absence of maternal vasculopathy.

Expression of aromatase in endometiosis and its relation to clinical laboratory and surgical parameters / 대한산부인과학회지

OBJECTIVE: Aromatase is the key enzyme for the conversion of C19 steroids into estrogen in certain human tissues. We studied to evaluate the aromatase expression in eutopic endometirum and endometriotic lesion and its relationship to clinical and laboratory parameters. METHODS: The study included 78 cases of endometriotic lesion and 14 cases of eutopic endometrium and 30 cases of normal uterine endometrium obtained through laparoscopic surgery and curettage. The frozen tissue specimens were examined by immunohistochemistry using aromatase. Clinical symptoms, laboratory findings, and operative findings were analyzed and compared in according to aromatase expression. RESULTS: We observed positive immunohistochemical expression for aromatase in endometriotic lesion from 46/78 patients (59.0%). Aromatase expression was elevated in comparison to eutopic endometrium (5/14 patients, P=0.032) and the difference was more pronounced when eutopic endometriums from patients with endometriosis were compared with those of healthy controls (2/30 patients, P<0.001). Aromatase-positive patients had more moderate-to-severe chronic pelvic pain, higher CA-125 level significantly. Also in operative findings, severe grade endometriosis, bilateral endometriomas, and associated leiomyoma and adenomyosis were more frequent in aromatase positive patients. High values of white blood cell count, erythrocyte sedimentation rate, CA 19-9 were more frequent in aromatase positive patients notwithstanding insignificant differences. CONCLUSION: Unopposed local biosynthesis of estrogens by increased expression of aromatase in eutopic endometrium and endometrial tissue could be involved in the development or maintenance of endometriosis and other uterine estrogen-triggered diseases. Our findings suggest increased expression of aromatase may be related with severity, activity, and chronic pelvic pain in patients with endometriosis.

A case of port site implantation of borderline mucinous tumor of ovary after the laparoscopic operation / 대한산부인과학회지

Borderline tumor of ovary is epithelial proliferation without stromal invasion, first reported by Taylor in 1929. Borderline ovarian tumor occurs in younger women and is detects in early stage. Laparosocopy is alternative treatment of younger women for postoperative quality of life because it reduces postoperative adhesion. But it is limited to incomplete staging, tumor cell dissemination and recurrence. We report a case of port site implantation of mucinous borderline tumor after the laparoscopic operation; usually recurrence of borderline tumors were occurred after ten or fifteen years later, this case a direct evidence of cause of metastasis after the laparoscopic operation.

A case of small bowel obstruction during pregnancy / 대한주산의학회잡지

Small bowel obstruction is an unusual complication of pregnancy, but it is associated with high fetal and maternal mortality. Diagnosis is often delayed due to confusion over symptoms by both the patient and physicians, because symptoms such as colicky abdominal pain, vomiting and constipation are all common at various stages of pregnancy. If is small bowel obstruction of gravid patient suspected, prompt abdominal radiological evaluation and surgical intervention to reduce both maternal and fetal mortality are warranted. We report a recently report a recently experienced case of small bowel obstruction with brief review of literatures.

Uterine Cervical Large Cell Neuroendocrine Carcinoma Concurrent with High Grade Squamous Intraepithelial Neoplasia: A Case Report

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy. We report a case of uterine cervical LCNEC concurrent with high grade squamous intraepithelial neoplasia (HG-SIN). The LCNEC expressed chromogranin A and thyroid transcription factor 1 (TTF1). The HG-SIN was negative for these markers. Human papillomavirus (HPV) type 18 was positive in LCNEC whereas both type 16 and 18 were positive in HG-SIN by nested polymerase chain reaction. This case showed TTF1 positivity nonetheless diagnosed as a primary uterine cervical LCNEC confirmed by the detection of HPV genome within the tumor. It is critical to recognize LCNEC of the uterine cervix even in the small biopsy specimen because it is a distinctive clinicopathological entity with highly aggressive behavior and unfavorable outcome.

A case of ovarian endometriosis after laparoscopically assisted vaginal hysterectomy / 대한산부인과학회지

Endometriosis is defined as the presence of endometrial tissue outside the uterus and located usually within the pelvis. It may be detected as a rare complication associated with surgery. Endometriosis following obstetric and gynecologic procedure, which is localized mostly in the surgical scar including Cesarean section scar, hysterotomy scar, trocar scar, Bartholin cyst exision scar, or episiotomy scar, may caused by implantation of endometrial gland and stroma. Endometriosis developing after hysterectomy, especially, is a quite rare condition except a recurrent disease. We have experienced a case of a 47-year-old woman who had diagnosed ovarian endometriosis two years after laparoscopically assisted vaginal hysterectomy for a large leiomyomatous uterus with no evidence of endometriosis, so we report this case with a brief review of literature.

A study on association of progesterone receptor gene polymorphism (PROGINS) with Endometriosis

PURPOSE: Endometriosis is a steroid dependent disease with a particular genetic background but the location of possible genomic aberrations are still poorly clarified. This study was designed to investigate the associations between the polymorphism of the progesterone receptor gene (PROGINS) and endometriosis. METHODS: 100 women with surgically diagnosed and histologically confirmed endometriosis were enrolled as a patient population and a total of 110 female control subjects undergoing health examination were enrolled as control population. DNA extraction and polymerase chain reaction (PCR) were used to genotype women for the presence of the PROGINS polymorphism in peripheral blood samples. The x2-test was used to compare genotype distributions between endometriosis and controls. RESULTS: T1/T2 heterozygote was found to be one patient in each group, and the rest of the subjects were all T1/T1 homozygotes. There was no difference in the genotype distribution between the endometriosis group and the control group. CONCLUSION: These results suggest that the progesterone receptor gene PROGINS is not associated with the risk for endometriosis.

A Case of Primary Carcinoma of the Fallopian Tube / 대한산부인과학회잡지

Primary carcinoma of the fallopian tube is very rare and accounts for less than 1% of all gynecologic malignancies. Nonspecific symptoms are presented, so primary carcinoma of the fallopian tube was confirmed postoperatively on the basis of the pathologic examination. The evaluation and treatment are similar to that of the ovarian cancer. We have experienced a case of primary carcinoma of the fallopian tube, especially fimbrial portion and report with a brief review of the literature

A Case of Huge Ovarian Tumor Associated with Hypothyroidism / 대한산부인과학회잡지

In adult women, hypothyroidism has significant effect on reproduction. Hypothyroidism is associated with oligomenorrhea, amenorrhea, anovulation, hypermenorrhea, menorrhagia, infertility, spontaneous abortion, stillbirth or preterm delivery. It can cause ovarian tumor, which clinically resembles ovarian hyperstimulation syndrome or multicystic ovarian tumor. We have experienced a case of spontaneously regressed huge ovarian tumor which was found in patient. With hypothyroidism. So we report this case with a brief review of literature.

Comparison of Expression of Endometrial Prolactin in infertile Women with Luteal Phase Defect According to Clomiphene Citrate Administration / 대한불임학회지

OBJECTIVE Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citrate-treated infertile women with luteal phase defect. METHODS: The endometrial samples from infertIle women wIth luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. RESULTS: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). CONCLUSION: in this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

Studies on Pregnanacy Rate of Controlled Ovarian Hyperstimulation before Intrauterine Insemination in the Treatment of Unexplained Infertility / 대한산부인과학회잡지

OBJECTIVE: To determine which regimen for controlled ovarian hyperstimulation is the most effective in achieving pregnancy after intrauterine insemination in the treatment of unexplained infertility. MATERIALS AND METHODS: From March 1996 to February 2000, a total of 67 cycles of intrauterine insemination after controlled ovarian hyperstimulation were treated in 39 patients under 40 years old who diagnosed as unexplained infertility. Two methods of controlled ovarian hyperstimulation were used. The one is clomiphene citrate/hMG and the other is hMG only. These were compared the pregnancy rate respectively. RESULTS: Mean age of study group was 32+/-2.7 years old (28-38 years old) and mean duration of infertility was 46+/-17.8 months (15-96 months). The overall clinical pregnancy rate was 17.9% (12/67 cycle) per cycle and 30.7% (12/39 patient) per patient. According to the methods of controlled ovarian hyperstimulation, pregnancy rate was 16.7% (8/48 cycle) after clomiphene citrate/hMG used, 21.1% (4/19 cycle) after hMG only used. 4 cases of ovarian hyperstimulation syndrome developed (clomiphene citrate/hMG 1 case, hMG only 3 cases) and all of them were self-regressed. CONCLUSION: Compared with using hMG only as controlled ovarian hyperstimulation before intrauterine insemination, using clomiphene citrate/hMG was more effective regimen and considered as the first choice in the treatment of unexplained infertility.

A Case of Holoprosencephaly / 대한산부인과학회잡지

Holoprosencephaly is a rare developmental defect due to incomplete cleavages of the prosencephalon during the third week of fetal development. It was associated with chromosomal anomalies, genetic syndrome, teratogen, or genetic disorder of non-syndromic HPE. Early antenatal detection of holoprosencephaly was done by high resolution ultrasonography. According to its severity and prognosis, it was capable of proper treatment of holoprosencephaly. We report one case of holoprosencephaly with a brief review of the literature

Vero Cell Co-culture Counteracts the Detrimental Effects of Hydrosalpinx Fluid on the Development of Mouse Embryos in vitro

Recent studies have suggested that the hydrosalpinx has a negative effect on pregnancy outcome, with markedly diminished implantation and increased early pregnancy loss. Fluid from the hydrosalpinx may leak into and accumulate in the uterine cavity. It is not clear, however if this creates a hostile local environment in the uterus for embryo implantation or exerts a direct embryotoxic effect. This study was conducted to investigate the detrimental effects of hydrosalpinx fluid (HSF) on the development of mouse embryos in vitro and to demonstrate whether Vero cells overcome these adverse effects. HSF was collected from three women with bilateral hydrosalpinx at the time of laparoscopic surgery. Collected fluid was centrifuged and the supernatant was frozen at -20degrees C. For co-culture, Vero cells were commercially obtained in a frozen state and cultured using Ham's F10 medium. Single-cell mouse embryos (B6CBAF1) were cultured for 5 days in 0, 0.4, 0.8, and 1.2% of HSF in media with and without Vero cells and examined daily to record the number of embryos reaching expanded blastocyst and hatching stage. Co-culture of mouse embryos with Vero cells at 0.8% HSF concentration significantly enhanced embryo development, but not at 1.2% hydrosalpinx fluid concentration. These results suggest that HSF is highly embryotoxic and Vero cells are likely to overcome these detrimental effects to some degree.