Elevated natural killer cell levels and autoimmunity synergistically decrease uterine blood flow during early pregnancy

OBJECTIVE: To investigate whether natural killer (NK) cell and autoimmune antibody acts synergistically, by the action of autoantibodies to increase NK cell number and cytotoxicity, to decrease uterine blood flow during early pregnancy in pregnant women with a history of recurrent spontaneous abortion (RSA). METHODS: Seventy-five pregnant women (between 5 and 7 weeks gestation) with a history of unexplained RSA were included in the study group. Forty-one pregnant women without a history of RSA were included as controls. All women with a history of RSA were tested for autoantibodies and number of peripheral blood natural killer (pbNK) cell by flow cytometry. Study populations were stratified into four groups by existence of autoantibody and degree of increase of pbNK cells. The uterine radial artery resistance index (RI) was measured by color-pulsed Doppler transvaginal ultrasound. RESULTS: The mean RI of the autoimmune antibody-positive (AA+) group (0.63+/-0.09) was significantly higher than that of the normal control group (0.53+/-0.10, P=0.001). The mean RI of the AA+/only-NK elevated (eNK) group (0.63+/-0.09) was significantly higher than those of the only-AA+ group (0.55+/-0.07, P=0.019) and the only-eNK group (0.57+/-0.07, P=0.021). CONCLUSION: Concurrent elevation in NK cells and autoimmunity results in decreased uterine blood flow during early pregnancy. However, the majority of cases of RSA remain unexplained and larger scale studies are needed to confirm our conclusion and to develop diagnostic and therapeutic plans for women with a history of RSA.

Age specific serum anti-Mullerian hormone levels in 1,298 Korean women with regular menstruation / 대한생식의학회지

OBJECTIVE: To determine the age specific serum anti-Mullerian hormone (AMH) reference values in Korean women with regular menstruation. METHODS: Between May, 2010 and January, 2011, the serum AMH levels were evaluated in a total of 1,298 women who have regular menstrual cycles aged between 20 and 50 years. Women were classified into 6 categories by age: 20-31 years, 32-34 years, 35-37 years, 38-40 years, 41-43 years, above 43 years. Measurement of serum AMH was measured by commercial enzyme-linked immunoassay. RESULTS: The serum AMH levels correlated negatively with age. The median AMH level of each age group was 4.20 ng/mL, 3.70 ng/mL, 2.60 ng/mL, 1.50 ng/mL, 1.30 ng/mL, and 0.60 ng/mL, respectively. The AMH values in the lower 5th percentile of each age group were 1.19 ng/mL, 0.60 ng/mL, 0.42 ng/mL, 0.27 ng/mL, 0.14 ng/mL, and 0.10 ng/mL, respectively. CONCLUSION: This study determined reference values of serum AMH in Korean women with regular menstruation. These values can be applied to clinical evaluation and treatment of infertile women.

Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study / 대한생식의학회지

OBJECTIVE: To investigate adverse pregnancy outcomes in non-obese women with polycystic ovary syndrome (PCOS) compared with obese-PCOS and control groups. METHODS: Women with PCOS who underwent assisted reproductive technology (ART) from August, 2003 to December, 2007, were considered. A total of 336 women with PCOS were included in the study group and 1,003 infertile women who had tubal factor as an indication for ART were collected as controls. They were divided into four groups: a non-obese PCOS group, obese-PCOS group, non-obese tubal factor group, and obese tubal factor group, with obesity defined by a body mass index over 25 kg/m2, and reviewed focusing on the basal characteristics, ART outcomes, and adverse pregnancy outcomes. RESULTS: There was no difference among the groups' the clinical pregnancy rate or live birth rate. Regarding adverse pregnancy outcomes, the miscarriage rate, multiple pregnancy rate, and prevalence of preterm delivery and pregnancy induced hypertension were not different among the four groups. The incidence of small for gestational age infant was higher in the PCOS groups than the tubal factor groups (p<0.02). On the other hand, the morbidity of gestational diabetes mellitus (GDM) was not high in the non-obese PCOS group but was in the obese groups. And in the obese PCOS group, the newborns were heavier than in the other groups (p<0.02). CONCLUSION: Non-obese PCOS presents many differences compared with obese PCOS, not only in the IVF-parameters but also in the morbidity of adverse pregnancy outcomes, especially in GDM and fetal macrosomia.

Midtrimester triple test in IVF/ICSI twin pregnancies / 대한산부인과학회지

OBJECTIVE: To compare the midtrimester triple marker levels for down syndrome screening between natural and IVF twin pregnancies and to evaluate the difference triple marker in IVF twin pregnancies according to the fertilization method and number of transferred embryos. METHODS: The study population consisted of conventional IVF twin (n=106), ICSI twin (n=142), and natural (n=436) twin pregnancies as controls between 2001 and 2004. All pregnancies in this study were known to have normal outcome. Maternal serum samples were collected between 14-18 gestational weeks. Levels of AFP, total hCG, and uE3 were measured and were expressed as multiples of the median (MoM) based on reference medians established at Cheil Hospital. RESULTS: The mean maternal age (31.6+/-2.8 vs. 31.6+/-3.0 vs. 32.1+/-2.1: conventional IVF group vs. ICSI group vs. control, respectively) and gestational weeks (16.0+/-0.5 vs. 16.0+/-0.7 vs. 16.1+/-0.2) for triple test were similar. There was no difference in levels of all serum markers between conventional IVF and ICSI group. The median AFP MoM for conventional IVF and ICSI group were significantly higher than that of the control group (2.40 vs. 2.22 vs. 1.98; p0.05). Also, the median hCG MoM was not different from that of the control group (2.04 vs. 2.06 vs. 2.02; p>0.05). There was no correlation in triple marker levels according to the number of transferred embryos in conventional IVF and ICSI groups. CONCLUSION: Midtrimester triple marker levels of IVF twin pregnancy for down syndrome screening are similar with those of natural twin pregnancy regardless of fertilization method and number of transferred embryos.

The Comparion of Pregnancy Outcomes between GnRH Agonist and GnRH Antagonist Cycles in Women with Advanced Age / 대한불임학회지

OBJECTIVE: To compare the clinical results and pregnancy outcomes of in vitro fertilization (IVF) between GnRH antagonist cycles and GnRH agonist (GnRH-a) cycles including flare-up and long protocol in women with advanced age. MATERIALS AND METHODS: Retrospective clinical study. From January 2001 to September 2003, IVF cycles of female patient 37 years over were included in this study. GnRH-a long protocol (62 cycles, 61 patients) and GnRH antagonist multi-dose flexible protocol (66 cycles, 51 patients) were compared with the control group of GnRH-a flare-up protocol (151 cycles, 138 patients). IVF cycles for non-obstructive azoospermia (NOA), endometriosis III, IV and polycystic ovarian syndrome (PCOS) were excluded in this study. Clinical results such as total gonadotropin dose, serum E2 on hCG administration, the number of retrieved oocytes and the pregnancy outcomes - clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate (LBR) per embryo transfer - were compared. RESULTS: There were significant differences in the total dose of gonadotropin (GnRH-a flare-up vs. GnRH-a long vs. GnRH-antagonist; 41.8 vs. 54.7 vs. 24.8), serum E2 on hCG administration (1787.2 vs. 1881.6 vs. 788.0), the numbers of retrieved oocytes (8.1 vs. 11.1 vs. 4.5) and endometrial thickness (9.1 vs. 10.4 vs. 8.0) which were significantly lower in GnRH-antagonist cycles. But pregnancy outcomes shows no significant differenced in CPR (25.0% vs. 35.8% vs. 24.5%), IR (11.7% vs. 12.3% vs. 10.1%) and LBR (15.8% vs. 28.3% vs. 15.1%) CONCLUSION: In women with advanced age, GnRH-antagonist cycles can result in comparable pregnancy outcomes to GnRH-a cycles including flare-up and long protocol. GnRH-a long protocol show higher CPR, IR and LBR than GnRH antagonist multi-dose flexible protocol and flare-up protocol without significant differences.