Lars Grabow Westergaard

1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study

OBJECTIVE To prospectively assess the reproductive outcome with a small bolus of hCG administered on the day of oocyte retrieval after ovulation induction with a GnRH agonist (GnRHa). DESIGN Prospective, randomized trial. SETTING Three hospital-based IVF clinics. PATIENT(S) Three hundred five IVF/intracytoplasmic sperm injection patients after a GnRH antagonist protocol. INTERVENTION(S) Ovulation induction was performed with either 10,000 IU hCG or 0.5 mg GnRHa (buserelin) supplemented with 1,500 IU hCG on the day of oocyte retrieval. MAIN OUTCOME MEASURE(S) Reproductive outcome in the two groups. RESULT(S) No significant differences were seen regarding positive hCG/ET rate (48% and 48%), ongoing pregnancy rate (26% and 33%), delivery rate (24% and 31%), and rate of early pregnancy loss (21% and 17%) between the GnRHa and 10,000 IU hCG groups, respectively. CONCLUSION(S) A small bolus of hCG in the GnRHa group secured the luteal phase, resulting in a comparable reproductive outcome in the two groups. However, a nonsignificant difference of 7% in delivery rates justifies further studies to refine the use of GnRHa for ovulation induction.

Number of germ cells and somatic cells in human fetal testes during the first weeks after sex differentiation

BACKGROUND This study presents the number of germ cells and somatic cells in human fetal testes during week 6 to week 9 post conception, i.e. the first weeks following sex differentiation of the testes. METHODS One testis with attached mesonephros from each of 10 individual legal abortions was used. After recovery of the fetus, the testes were immediately isolated, fixed and processed for histology. The optical fractionator technique, a stereological method, was utilized to estimate the total number of germ cells in ten testes and somatic cells in six of them. RESULTS The number of germ cells per testis increased from approximately 3000 in week 6 to approximately 30000 in week 9. The ratio of germ cells to Sertoli cells was approximately 1:11 and the ratio of germ cells to somatic cells was approximately 1:44 throughout this period. CONCLUSIONS For the first time, germ cell and somatic cell number have been determined during early human fetal testis development. Knowledge of the number of germ cells in this period may be very important, because several environmental pollutants are suspected to result in decreased semen quality in men born of mothers exposed to these pollutants during pregnancy.

Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study

OBJECTIVE To evaluate clinical and endocrinological effects of intranasal (IN) vs. subcutaneous (SC) GnRH-a for pituitary down-regulation combined with hMG vs. rFSH. DESIGN Prospective, randomized study. SETTING University hospital, IVF unit. PATIENT(S) Three hundred seventy-nine normogonadotropic women eligible for IVF or ICSI. INTERVENTION(S) Randomization to intranasal (IN) or SC GnRH-a and to hMG or rFSH. MAIN OUTCOME MEASURE(S) Oocytes retrieved, embryos developed, clinical pregnancy, and delivery rates. Serum hormone concentrations on stimulation days 1 (S1) and 8 (S8), and oocyte pick-up (OPU) day. RESULT(S) After randomization, four groups were formed: IN/hMG (n = 100), IN/FSH (n = 98), SC/hMG (n = 89), and SC/FSH (n = 92). Mean number of oocytes retrieved and of transferable and transferred embryos were similar in the four groups. Clinical pregnancy rate per started cycle was significantly higher in the IN/HMG group than in the SC/FSH group (P<.05) and was intermediate in the two remaining groups. Se-LH on S8 in the two SC groups was significantly lower than in the two IN groups. Se-E2 on S8 in the SC/FSH group was significantly lower than in the other three groups. CONCLUSION(S) The clinical and endocrinological outcome in IVF and ICSI-treated normogonadotropic women is significantly influenced by mode of down-regulation as well as gonadotropin formulation.

Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles

Objective. To identify prognostic factors influencing the outcome of infertility treatment using homologous intrauterine inseminations (IUI‐H).

Effectiveness of human menopausal gonadotropin versus recombinant follicle-stimulating hormone for controlled ovarian hyperstimulation in assisted reproductive cycles: a meta-analysis

OBJECTIVE To compare the effectiveness of hMG and recombinant FSH after down-regulation for ovulation stimulation in assisted reproductive cycles. DESIGN Meta-analysis. SETTING Infertility centers providing assisted reproductive techniques. PATIENT(S) Two thousand thirty women undergoing IVF or ICSI. INTERVENTIONS Ovarian hyperstimulation with hMG or recombinant FSH after down-regulation. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate, ongoing pregnancy/live birth rate, gonadotropin dose used, oocytes retrieved, implantation rate, miscarriage rate, and multiple pregnancy rate. RESULT(S) Six randomized controlled trials were included. In all trials, the group of women treated with hMG had higher pregnancy rates. Pooling the five trials that used a long GnRH agonist protocol resulted in a higher clinical pregnancy rate for hMG compared with recombinant FSH (relative risk, 1.22 [95% CI, 1.03 to 1.44]). However, there was no evidence of a difference in rates of ongoing pregnancy or live birth per woman between hMG recipients and recombinant FSH recipients (relative risk, 1.20 [95% CI, 0.99 to 1.45]). No differences were found in gonadotropin dose used, oocytes retrieved, miscarriage rate, or multiple pregnancy rate. CONCLUSION(S) Use of hMG resulted in higher clinical pregnancy rates than did use of recombinant FSH in IVF/ICSI cycles after GnRH agonist down-regulation in a long protocol.

Anti-Mullerian hormone remains highly expressed in human cumulus cells during the final stages of folliculogenesis

This study evaluated whether anti-Müllerian hormone (AMH) was differentially expressed in cumulus (CC) and granulosa (GC) cells from large antral and pre-ovulatory follicles collected from individual follicles in women undergoing in-vitro maturation (IVM) or IVF treatment. Expression studies of AMH, AMH receptor 2, FSH receptor, aromatase and androgen receptor were performed in CC in IVM patients where cumulus-oocyte-complex had expanded, CC in IVM patients where cumulus-oocyte-complex remained compacted, GC from immature follicles and CC and GC from IVF patients. Microarray data on corresponding GC and CC from follicles from IVF patients was included. AMH expression was significantly higher in CC than in GC from both mature and immature follicles and in CC from immature follicles than in CC from pre-ovulatory follicles from IVF patients (P < 0.05). AMH expression was significantly higher in CC that remained compacted compared with those that had expanded (P < 0.008). AMH was correlated to the expression of FSH receptor, androgen receptor and AMH receptor 2 but not to aromatase expression. The expression pattern of AMH receptor 2 reflected that of AMH. AMH may exert intrafollicular functions even in human large antral and pre-ovulatory follicles and may be related to follicular health.

Concentrations of Anti-Müllerian Hormone in fluid from small human antral follicles show a negative correlation with CYP19 mRNA expression in the corresponding granulosa cells

Ovaries surgically removed for fertility preservation from a total of 24 women served as a source of human small antral follicles, including the follicular fluid (FF) and the corresponding granulosa cells (GC). The FF was used to evaluate the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B, estradiol, progesterone, androstenedione and testosterone. In GC mRNA expression of the AMH type II receptor (AMH-r2) was determined and correlated to the mRNA expression of CYP19 (aromatase), FSH-receptor (FSH-r) and LH-receptor (LH-r) and to the hormonal profiles of the corresponding FF. GC and FF from a total of 64 follicles (diameter of 3-9 mm) were evaluated. Concentrations of AMH in FF showed a highly significant inverse correlation with CYP19 mRNA expression in the corresponding GC and with concentrations of estradiol, progesterone and inhibin-B in the FF. However, a small subgroup of follicles exhibited high levels of AMH simultaneously with relative high levels of CYP19 mRNA. In contrast to AMH, mRNA expression of AMH-r2 was significantly positively correlated to the mRNA expression of FSH-r and CYP 19, but failed to correlate to any other measured parameters. These data confirms an intimate correlation between follicular AMH levels, AMH-r2, FSH-r expression and estradiol secretion in the developing human follicle.

FSH isoform composition of commercial gonadotrophin preparations: a neglected aspect?

The clinical efficacy of commercial gonadotrophin preparations has been the subject of an intense debate during recent years. Arguments have primarily focused on the origin of FSH activity (urine versus recombinant derived) and whether the preparation included LH-like activity. FSH isoform composition has received little or no attention, and is usually considered to have negligible effect on clinical effectiveness. By presenting the available data on the FSH isoform composition of commercial gonadotrophin preparations, the present paper challenges this assumption. To evaluate whether the FSH isoform composition affected the efficacy of a product, a meta-analysis was performed that compared a preparation expressing an acidic isoform profile (urinary-derived Metrodin-HP) with a preparation rich in less acidic isoforms (recombinant derived Gonal F). A total of five randomized clinical trials that specifically compared these two preparations was identified and included in the analysis. All parameters relating to the direct effect of FSH on the follicle differed significantly in favour of the product rich in less acidic isoforms, while data on pregnancy outcome did not reach significance. The importance of the FSH isoform profile and whether the FSH is derived from urine or by recombinant technique is discussed in relation to clinical efficacy. It is suggested that the FSH isoform profile of commercial gonadotrophin preparations is of clinical importance and should be taken into account when evaluating efficacy.

Intrauterine insemination with donor semen. An evaluation of prognostic factors based on a review of 1131 cycles

Objective. To identify prognostic factors influencing the outcome of infertility treatment using intrauterine insemination with donor semen (IUI‐D).

Levels of the epidermal growth factor-like peptide amphiregulin in follicular fluid reflect the mode of triggering ovulation: a comparison between gonadotrophin-releasing hormone agonist and urinary human chorionic gonadotrophin

OBJECTIVE To detect differences in follicular fluid (FF) levels of amphiregulin (AR), depending on mode of triggering final oocyte maturation. DESIGN Prospective randomized trial. SETTING Three IVF units. PATIENT(S) Ninety-six patients undergoing IVF-intracytoplasmic sperm injection. INTERVENTION(S) Ovulation triggered with either urinary hCG or GnRH agonist (GnRH-a). CONTROLS 15 FF samples from small antral follicles (3-9 mm) and 12 FF samples from natural cycle. MAIN OUTCOME MEASURE(S) Follicular fluid concentration of AR, P4, E2, vascular endothelial growth factor, and inhibin B. RESULT(S) Significantly lower levels of AR were found in FF from the GnRH-a group versus the hCG group, 51±3.5 versus 71±6.0 ng/mL. In FF from natural cycles, levels of AR were significantly higher than those of GnRH-a triggering but significantly lower than those of urinary hCG triggering. In small antral follicles only 5 out of 15 follicles contained measurable amounts of AR. When urinary hCG and GnRH-a triggering were compared, FF P4 was significantly higher after urinary hCG triggering, whereas no difference was seen regarding E2, vascular endothelial growth factor, and inhibin B. A total of 14% more metaphase II oocytes and 11% more transferable embryos were obtained after GnRH-a triggering. CONCLUSION(S) This study suggests that oocyte competence is linked to granulosa cell AR secretion.