Lgr4 is one of the genes identified as novel G protein–coupled receptor genes designated Lgr4–Lgr8, with high homology with FSH receptor, LH receptor, and TSH receptor genes, but studies of Lgr4-mutant mice have suggested that Lgr4 has essential functions in development. This is the first report describing the relationship between the functions of Lgr4 and female reproductive systems.

Objective: To compare early follicular growth after fresh and frozen-thawed human ovarian tissue xenografting and to investigate whether expression of c-kit, kit ligand (KL), and growth differentiation factor-9 (GDF-9) is maintained after freezing and xenografting of human ovarian tissue.Design: Prospective experimental study.Setting: Gynecology research unit in a university hospital.Animal(s): Ten nude (Swiss nu/nu) 6-week-old female mice.Intervention(s): The ovarian biopsy samples were obtained from six women, aged 20 to 30 years. Fresh and frozen-thawed ovarian fragments intraperitoneally grafted into nude mice for 3 weeks.Main Outcome Measure(s): Histologic analysis and immunohistochemical evaluation of c-kit, KL, and GDF-9 expression before and after grafting.Result(s): The integrity and proportion of growing follicles increased similarly in both fresh (64%) and frozen-thawed (59%) xenografts compared with non-grafted tissue (fresh: 40%; frozen-thawed: 21%). Both C-kit and KL staining were detected in the oocytes and granulosa cells of preantral follicles, and GDF-9 expression was observed in the oocytes of preantral follicles in all groups.Conclusion(s): Freezing does not appear to have a major impact on early follicular growth after transplantation. This study shows, for the first time, expression of c-kit, KL, and GDF-9 in human preantral follicles after ovarian tissue cryopreservation and xenotransplantation.

In 36 women with polycystic ovary syndrome and clomiphene citrate resistance, letrozole, an aromatase inhibitor, statistically significantly increased the ovulation rate by 33.3% in the treatment group, indicating that letrozole can be used as an effective and simple alternate ovulation-inducing agent in these women.

In infertile women suffering from polycystic ovary syndrome (PCOS), anti-thyroid peroxidase antibodies values exceeding the upper level of normal were found in significantly more clomiphene citrate resistant patients compared clomiphene citrate responders and metformin responders. Thus, elevated antiTPO levels are associated with poor treatment response in infertile women who suffer from PCOS.

Objective: To evaluate a possible correlation between transvaginal ultrasound findings in miscarriages and cytogenetic analyses from chorionic villi obtained by dilatation and curettage.Design: Prospective, population-based study.Setting: University-based hospital.Patient(s): Five hundred seventy-six women with spontaneous miscarriage diagnosed between 6 and 12 completed pregnancy weeks.Intervention(s): Transvaginal ultrasonography and dilatation and curettage.Main Outcome Measure(s): Cytogenetic analyses and ultrasound measurement of embryonic pole.Result(s): The mean gestational age was 9.5 weeks. Chromosomal analyses were successful in 259 cases, 159 with cytogenetic abnormalities and 100 euploidy. Empty gestational sacs were equally often found in euploidy and aneuploidy, whereas small embryonic or fetal poles were significantly more often associated with aneuploidy.Conclusion(s): A smaller than expected fetal size when a miscarriage is diagnosed during the first trimester is significantly associated with a chromosomal aberration.

Objective: To evaluate the importance of subjecting the patient to an outpatient (office) hysteroscopy (OH) before assisted reproductive techniques (ART) and patient compliance, possible side effects, and complications of the procedure.Design: Comparative observational cross-sectional study.Setting: University hospital.Patient(s): One hundred fifty-two patients attending the outpatient infertility clinic for pre-ART (IVF/intracytoplasmic sperm injection [ICSI]-ET) investigations, with normal uterine findings on hysterosalpingography (HSG).Intervention(s): Transvaginal sonography (TVS) and OH (using a rigid, 30-degree, 4-mm hysteroscope) by the vaginoscopic “no touch” technique.Main Outcome Measure(s): Diagnostic value and compliance of OH.Result(s): The procedure was successful in 145 patients (95.4%); 51 of them (35.2%) had previous ART failures. Abnormal hysteroscopic findings were observed in 48 women (33.1%), in which endometrial polyp, submucous myoma, and intrauterine adhesions were the most common findings. The TVS was specific (100%) but not sensitive (41.7%) compared with OH. Abnormal hysteroscopic findings were significantly higher in patients with previous ART failure(s). The procedure was acceptable in almost all patients with no reported complications.Conclusion(s): The OH should be part of the infertility workup before ART even in patients with normal HSG and/or TVS. This is especially relevant in cases with prior failed ART cycles.

Objective: To compare different methods of ovarian stimulation (OS) for assisted reproductive technology in baboons.Design: Prospective randomized study.Setting: Institute of primate research.Animal(s): Baboons (n = 10) were randomized into two groups (of five animals each) during three different cycles to compare six protocols of OS.Intervention(s): Cycle 1: clomiphene citrate (CC) alone (group CC) versus CC and GnRH agonist (group CC-Ag); cycle 2: recombinant gonadotropins (GON) without GnRH agonist (group GON) versus GON and depot GnRH agonist (group GON-AgDepo-1); cycle 3: GON and depot GnRH agonist (group GON-AgDepo-2) versus GON and daily GnRH agonist in a classic long protocol (group GON-Ag). Oocyte aspiration was performed 34–36 hours after injecting 5,000 IU rhCG, followed by fertilization via intracytoplasmic sperm injection (ICSI).Main Outcome Measure(s): Number and quality of oocytes retrieved and their fertilization rate.Result(s): More metaphase II (MII) oocytes were retrieved using the GON-AgDepo-1 (n = 12; 64% MII), GON-AgDepo-2 (n = 9; 79% MII), GON-Ag (n = 16; 88% MII), and GON (n = 6; 59% MII) protocols compared with the CC (n = 9; 15% MII) and CC-Ag (n = 14; 20% MII) protocols. Fertilization by ICSI varied between 43% and 71%.Conclusion(s): In baboons, long and depot protocols yield similar numbers of MII oocytes; however, depot protocol may be preferable because only one injection of GnRH agonist is needed.

Objective: To evaluate whether the incidence of luteinizing hormone (LH) rise is reduced by using a flexible compared with a fixed day-6 protocol of GnRH antagonist administration.Design: Randomized controlled trial.Setting: Tertiary university hospital.Patient(s): Patients undergoing in vitro fertilization (n = 146).Intervention(s): Ovarian stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist cetrorelix (0.25 mg/d) was started either on day 6 of stimulation (fixed group) or when LH was >10 IU/L, and/or a follicle with mean diameter >12 mm was present, and/or serum E2 was >150 pg/mL. Patient monitoring was initiated on day 3 of stimulation.Main Outcome Measure(s): Incidence of LH rise.Result(s): No statistically significant difference was observed between the flexible and fixed groups regarding the incidence of LH rise, which was lower in the flexible group (11.0% vs. 15.1%, difference −4.1%, 95% confidence interval −15.4% to +7.1%). No LH surges were observed in any of the patients studied.Conclusion(s): Flexible antagonist administration from day 3 onward does not appear to reduce the incidence of LH rises compared with fixed antagonist administration on day 6 of stimulation.

Objective: To determine the feasibility of performing in vivo magnetic resonance elastography (MRE) for uterine leiomyoma.Design: Pilot study.Setting: Academic medical center.Patient(s): Six subjects planning surgical excision of uterine leiomyomas.Intervention(s): MRE before planned surgery.Main Outcome Measure(s): Achieving an appropriate phase signal–to-noise ratio (PSNR) in the leiomyoma to allow assessment of leiomyoma elasticity in kilopascals (kPa).Result(s): MRE was successful in all subjects for uteri ranging from 100 to >1,000 g. Subjects had body mass indexes ranging from 23.0 to 38.0 kg/m2. Appropriate PSNRs, ranging from 5.45 to 42.28, were achieved for leiomyomas in all subjects. Mean elasticity of uterine leiomyomas ranged from 3.95 to 6.68 kPa.Conclusion(s): MRE is a feasible technique for studying the in vivo mechanical properties of uterine leiomyomas and demonstrates significant heterogeneity in elasticity between lesions. Further work is necessary to optimize the technique and understand the clinical utility of this technique for women with uterine leiomyomas.

In a retrospective study comparing 526 oocyte donors who received prophylactic antibiotics for oocyte retrieval with a comparable group of 625 who did not, the incidence of infection after retrieval was reduced from 0.4% to 0 in the group receiving antibiotics. Donors take risks but have no medical indication for the procedures that they undergo; our data suggest that prophylactic antibiotics at retrieval should be considered to minimize the risk of infection.