Chung-Hoon Kim

Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization/intracytoplasmic sperm injection

OBJECTIVEnTo investigate whether levothyroxine (LT4) treatment has beneficial effects on IVF results and pregnancy outcome in infertile patients with subclinical hypothyroidism undergoing IVF/intracytoplasmic sperm injection (ICSI).nnnDESIGNnProspective, randomized trial.nnnSETTINGnUniversity-affiliated infertility clinic.nnnPATIENT(S)nA total of 64 infertile patients with subclinical hypothyroidism, defined as an elevated serum TSH level associated with a normal free T4 level and without frank symptoms of hypothyroidism.nnnINTERVENTION(S)nPatients were randomized into an LT4 treatment group or control group. For the LT4 treatment group, 50 μg LT4 was administered from the first day of controlled ovarian stimulation for IVF/ICSI.nnnMAIN OUTCOME MEASURE(S)nResults of IVF and pregnancy outcome.nnnRESULT(S)nThere were no differences in patient characteristics between the two groups. Total dose and days of recombinant human FSH used for controlled ovarian stimulation were also similar. The number of grade I or II embryos was significantly higher in the LT4 treatment group than in the control group. There was no significant difference in the clinical pregnancy rate per cycle between the two groups. However, the miscarriage rate was significantly lower in the LT4 treatment group than in the control group. Embryo implantation rate and live birth rate were significantly higher in the LT4 treatment group. In the control group, both thyroid peroxidase antibody and thyroglobulin antibody levels were significantly higher in the miscarried subgroup than in the delivered subgroup.nnnCONCLUSION(S)nLT4 treatment can improve embryo quality and pregnancy outcome in subclinical hypothyroid women undergoing IVF/ICSI.

Increased plasma levels of phthalate esters in women with advanced-stage endometriosis: a prospective case-control study.

We performed the present prospective case-control study to evaluate whether the plasma concentrations of phthalate esters are elevated in women with advanced-stage endometriosis in a Korean population. Measuring plasma levels of monoethylhexyl phthalate and di-(2-ethylhexyl) phthalate in 97 women with advanced-stage endometriosis and 169 control women by liquid chromatography-tandem mass spectrometry, we found that the concentrations of monoethylhexyl phthalate, as well as di-(2-ethylhexyl) phthalate, are significantly higher in those with advanced-stage endometriosis, which supports the hypothesis that exposure to phthalate might play a role in the establishment of endometriosis.

Decline of serum antimüllerian hormone levels after laparoscopic ovarian cystectomy in endometrioma and other benign cysts: a prospective cohort study

OBJECTIVEnTo identify the most important factor in predicting ovarian reserve after laparoscopic ovarian cystectomy and to evaluate whether there is any difference in the postoperative decline of ovarian reserve between women with endometrioma and those with other benign ovarian cysts.nnnDESIGNnProspective cohort study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nA total of 100 women who had undergone laparoscopic ovarian cystectomy for endometrioma (n = 68) or other benign ovarian cysts (n = 32).nnnINTERVENTION(S)nSerum antimüllerian hormone (AMH) levels measured by enzyme immunoassay preoperatively and at 3 months after surgery.nnnMAIN OUTCOME MEASURE(S)nRate of AMH decline after surgery and follicle numbers retained in cystectomy specimens.nnnRESULT(S)nSerum AMH levels were obviously decreased at 3 months after the surgery (4.97 ± 2.83 vs. 3.33 ± 2.08 ng/mL, mean ± standard deviation). Adjusting for several parameters, we could see that bilaterality of the ovarian cyst was the only significant factor in predicting the rate of postoperative decline of AMH levels. The rate of AMH decline did not differ between the endometrioma group and the other benign ovarian cyst group.nnnCONCLUSION(S)nBilaterality of the ovarian cyst is the only significant factor in predicting the rate of decline of AMH level after laparoscopic ovarian cystectomy. The rate of decline of AMH levels after surgery was similar between the endometrioma group and the other benign ovarian cyst group.

Update on the treatment of endometriosis

Endometriosis is defined as the presence of functional endometrial tissue outside the uterus, causing diverse progressive symptoms such as infertility, pelvic pain, and dysmenorrhea. Although endometriosis has been described since the 1800s, the mechanisms responsible for its pathogenesis and progression remain poorly understood. It is well established that endometriosis grows and regresses in an estrogen-dependent fashion and the disease can be effectively cured by definitive surgery. However, prolonged medical therapy may be needed in most of the cases since conservative surgery is usually performed especially in young women. This treatment modality is often associated with only partial relief and/or recurrence of the disease. In the present review, up-to-date findings on the treatment of endometriosis will be briefly summarized. The outcomes of surgery in patients with endometriosis will be reviewed in terms of pelvic pain relief as well as infertility treatment largely based on recent Cochrane reviews and clinical reports. The efficacy of newer drugs including aromatase inhibitor, anti-tumor necrosis factor-alpha, and dienogest will be also reviewed based on recent clinical studies.

Minimal stimulation using gonadotropin-releasing hormone (GnRH) antagonist and recombinant human follicle-stimulating hormone versus GnRH antagonist multiple-dose protocol in low responders undergoing in vitro fertilization/intracytoplasmic sperm injection

This prospective randomized study was performed to investigate the effectiveness of minimal stimulation using recombinant human FSH (rhFSH) and GnRH antagonist compared with GnRH antagonist multiple-dose protocol (MDP) in low responders undergoing IVF/intracytoplasmic sperm injection. Our study demonstrated that minimal stimulation in natural cycles provides similar pregnancy rates to the GnRH antagonist MDP with fewer dose and days of rhFSH used and thus can be a cost-effective alternative as a last chance before oocyte donation in low responders.

Possible Role of Phthalate in the Pathogenesis of Endometriosis: In Vitro, Animal, and Human Data

CONTEXTnAlthough phthalates were shown to have several negative effects on reproductive function in animals, its role in the pathogenesis of endometriosis remains to be elucidated.nnnOBJECTIVEnWe aimed to investigate the in vitro and in vivo effects of di-(2-ethylhexyl)-phthalate (DEHP) and to compare the urinary levels of several phthalate metabolites between women with and without endometriosis.nnnDESIGNnFor experimental studies, we used endometrial cell culture and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse models. We also performed a prospective case-control study for human sample analyses.nnnSETTINGnThe study was conducted at an academic center.nnnMAIN OUTCOME MEASURESnThe activities of matrix metalloproteinase (MMP)-2 and 9, cellular invasiveness, phosphorylation of extracellular signal-regulated kinase (Erk), and expression of p21-activated kinase 4 were analyzed in endometrial cells treated with DEHP. The implant size was compared between NOD/SCID mice fed with and without DEHP. Urinary concentrations of several phthalate metabolites were compared between women with and without endometriosis.nnnRESULTSnIn vitro treatment of endometrial cells with DEHP led to significant increases of MMP-2 and 9 activities, cellular invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression. The size of the endometrial implant was significantly larger in the NOD/SCID mice fed with DEHP compared with those fed with vehicle. The urinary concentration of mono (2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate, and mono (2-ethyl-5-carboxyphentyl) phthalate were significantly higher in women with endometriosis compared with controls.nnnCONCLUSIONnThese findings strongly suggest that exposure to phthalate may lead to establishment of endometriosis by enhancing invasive and proliferative activities of endometrial cells.

Increased viability of endometrial cells by in vitro treatment with di-(2-ethylhexyl) phthalate

Based on the findings of several reports that have shown an increased plasma level of di-(2-ethylhexyl) phthalate (DEHP) in women with endometriosis, the present study was designed to evaluate whether in vitro treatment with DEHP can increase viability of endometrial cells. Utilizing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay, fluorescent activated cell sorter analysis, and microscopic evaluation after Hoechst staining, we revealed that in vitro treatment with DEHP leads to increased viability of Ishikawa cells as well as endometrial stromal cells in serum-free condition and following exposure to hydrogen peroxide, which suggests that exposure to phthalate might play a role in the establishment of endometriosis.

Influence of Antiphospholipid Antibodies on Pregnancy Outcome in Women Undergoing In Vitro Fertilization and Embryo Transfer

Problemu2002 Antiphospholipid antibodies (APA) are thought to be involved in recurrent pregnancy loss. Therefore, we investigated the impact of APA on pregnancy outcome in women undergoing in vitro fertilization and embryo transfer (IVF‐ET).

The effect of luteal phase progesterone supplementation on natural frozen-thawed embryo transfer cycles

Objective To evaluate the effect of progesterone supplementation during the luteal phase on pregnancy outcome in natural frozen-thawed embyo transfer (FTET) cycles. Methods In this retrospective cohort study, 228 consecutive patients who underwent FTET cycles between January 2009 and September 2012 were included. One hundred forty-five patients received luteal progesterone support (P group) but 83 patients did not receive any progesterone supplementation during luteal phase (control group). Results There were no differences in patients characteristics between the two groups. The two groups were similar with respect to the characteristics of previous fresh in vitro fertilization cycle in which embryos were cryopreserved including the numbers of oocytes retrieved, mature oocytes, fertilized oocytes, grade 1 or 2 embryos and frozen embryos. Also, significant differences were not observed between the P and control groups in clinical pregnancy rate, embryo implantation rate and multiple pregnancy rate. However, miscarriage rate was significantly lower in the P group and live birth rate was significantly higher in the P group than in the control group (P<0.05, P<0.05). Conclusion Our results suggest that luteal phase progesterone supplementation decreases miscarriage rate and improves live birth rate in natural FTET cycles.

GnRH antagonist multiple dose protocol with oral contraceptive pill pretreatment in poor responders undergoing IVF/ICSI

Objective To investigate the effectiveness of GnRH antagonist multiple-dose protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment and GnRH agonist low-dose long protocol (LP). Methods A total of 120 poor responders were randomized into three groups according to controlled ovarian stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1), GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low-dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were pretreated with OCP for 21days in the cycle preceding COS, and ovarian stimulation using recombinant human FSH (rhFSH) was started 5 days after discontinuation of OCP. Results There were no differences in patients characteristics among three groups. Total dose and days of rhFSH used for COS were significantly higher in group 3 than in group 1 or 2. The numbers of mature oocytes, fertilized oocytes and grade I, II embryos were significantly lower in group 2 than in group 1 or 3. There were no significant differences in the clinical pregnancy rate and implantation rate among three groups. Conclusion GnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH agonist low-dose LP in poor responders and can benefit the poor responders by reducing the amount and duration of FSH required for follicular maturation.