L. Engmann

Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization

OBJECTIVE To determine the role of endometrial sampling for identification and treatment of chronic endometritis (CE) in patients undergoing IVF-ET who repeatedly failed to conceive despite the transfer of good-quality embryos. DESIGN Retrospective chart review. SETTING University-based tertiary fertility center. PATIENT(S) Thirty-three patients with recurrent implantation failure (RIF) who underwent endometrial sampling and subsequent ET were analyzed based on immunohistochemically confirmed CE: CE present on biopsy (group 1; n = 10) and CE absent on biopsy (group 2; n = 23). Patients with RIF undergoing IVF cycles during the same time period who did not have endometrial sampling were used as controls (group 3; n = 485). INTERVENTION(S) Endometrial sampling for CE and subsequent antibiotic treatment in affected patients followed by another IVF-ET cycle. RESULT(S) Chronic endometritis was identified in 30.3% of patients with RIF. Group 1 had lower implantation rates (11.5%) in the IVF cycle following treatment than did group 2 and group 3 (32.7% and 20.3%, respectively). Clinical pregnancy and ongoing pregnancy rates were similar across groups. CONCLUSION(S) Recurrent implantation failure warrants investigation of CE as a contributing factor. Women demonstrating CE on endometrial sampling have lower implantation rates in a subsequent IVF-ET cycle; however, there were no differences in subsequent clinical pregnancy or ongoing pregnancy rates after successful antibiotic treatment.

Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders

OBJECTIVE To compare live birth rates after dual trigger of oocyte maturation with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders with peak E(2) <4,000 pg/mL at risk of ovarian hyperstimulation syndrome (OHSS). DESIGN Retrospective cohort study. SETTING University-based tertiary-care fertility center. PATIENT(S) Patients <40 years old with peak E(2) <4,000 pg/mL at risk of OHSS who underwent IVF/intracytoplasmic sperm injection with GnRH antagonist protocol and triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation. INTERVENTION(S) GnRHa alone versus dual trigger. MAIN OUTCOME MEASURE(S) Live birth, implantation, and clinical pregnancy rates and OHSS. RESULT(S) The dual-trigger group had a significantly higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%), and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger group. One case of mild OHSS occurred in the dual-trigger group, and there were no cases of OHSS in the GnRHa trigger group. CONCLUSION(S) Dual trigger of oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2) <4,000 pg/mL improves the probability of conception and live birth without increasing the risk of significant OHSS.

GnRH agonist to induce oocyte maturation during IVF in patients at high risk of OHSS

The aim of this retrospective study was to evaluate the effectiveness of gonadotrophin-releasing hormone agonist (GnRHa) to trigger oocyte maturation in patients with polycystic ovarian syndrome (PCOS) or previous high response. The outcome of ovarian stimulation and IVF in patients using GnRHa to trigger oocyte maturation after co-treatment with GnRH antagonist (study group) was compared with patients using human chorionic gonadotrophin (HCG) to trigger oocyte maturation after a dual pituitary suppression protocol with oral contraceptive pill (OCP) and GnRHa overlap (control group). All patients received intramuscular progesterone for luteal support but patients in the study group received additional supplementation with oestradiol patches. The mean number of oocytes, proportion of mature oocytes and fertilization rate were similar between the study and control groups. Implantation rate (38.6% versus 45.1%), clinical pregnancy rate (69.6% versus 60.9%) and delivery rate (62.5% versus 56.5%) were similar in the study and control groups respectively. There was one case of moderate ovarian hyperstimulation syndrome (OHSS) in the control group and none in the study group. GnRHa is effective in triggering oocyte maturation in patients with PCOS or previous high response. Further randomized studies are required to evaluate its effectiveness in the prevention of OHSS in this group of patients.

Cumulative probability of clinical pregnancy and live birth after a multiple cycle IVF package: a more realistic assessment of overall and age-specific success rates?

Objective To provide an assessment of pregnancy and live birth probabilities for women presenting for in vitro fertilisation treatment for the first time, when committed in advance to have up to three cycles of treatment in one year.

Agonist trigger: what is the best approach? Agonist trigger with aggressive luteal support

Although gonadotropin-releasing hormone agonist (GnRHa) trigger is effective in the prevention of ovarian hyperstimulation syndrome, lower conception rates have been reported. Intensive luteal phase support is an effective approach to improve implantation rates in women with peak E(2) levels ≥ 4,000 pg/mL. However, patients with peak E(2) levels <4,000 pg/mL may require a dual trigger with GnRHa and 1,000 IU hCG and intensive luteal phase support to improve implantation rates.

Predicting successful induction of oocyte maturation after gonadotropin-releasing hormone agonist (GnRHa) trigger

STUDY QUESTION Are there factors predicting the number of total and mature oocytes retrieved after controlled ovarian hyperstimulation (COH) utilizing a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist (GnRHa) to induce oocyte maturation? SUMMARY ANSWER Peak estradiol (E₂) level, post-trigger LH and progesterone and the magnitude of LH rise are independent predictors of the total number of oocytes and mature oocytes retrieved. WHAT IS KNOWN ALREADY Despite multiple follicular development in high responders, oocyte retrieval after a GnRHa trigger in a small subset of patients fails to obtain a substantial number of total oocytes or mature oocytes. STUDY DESIGN, SIZE AND DURATION A retrospective chart review of all autologous and oocyte donation cycles utilizing a GnRHa antagonist protocol where GnRHa was used for the induction of oocyte maturation between 1 April 2003 and 31 December 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS A total of 508 autologous and donor IVF/ICSI cycles utilizing a GnRH antagonist protocol for COH and GnRHa for the induction of oocyte maturation at a university-based tertiary fertility center. MAIN RESULTS AND THE ROLE OF CHANCE Peak E₂ on the day of trigger (r = 0.19, P < 0.001), post-trigger LH (r = 0.12, P = 0.009) and progesterone (r = 0.47, P < 001) and LH rise (r = 0.18, P < 0.001) all positively correlated with the number of total and mature oocytes retrieved. The true incidence of empty follicle syndrome was 1.4% (7/508). There was no post-trigger LH or progesterone cut-off value for the prediction of oocyte yield. However, all cases of empty follicle syndrome occurred in patients with post-trigger LH <15 IU/l and P ≤ 3.5 ng/ml. The findings of this study may also be due to chance since it was a retrospective study and not prospectively designed. LIMITATION, REASONS FOR CAUTION This is a retrospective chart review and therefore subject to bias. Serum hormone measurements were performed between 8 and 12 h after GnRHa trigger rather than a standardized time period following trigger administration. Therefore, peak levels of LH may have been missed due to the short ascending limb of LH rise lasting approximately 4 h after GnRHa trigger. WIDER IMPLICATIONS OF THE FINDINGS The results of this study can be generalized to high responders utilizing a GnRH antagonist protocol for COH and a GnRHa for the induction of oocyte maturation. The use of alternative stimulation regimens or medications will limit the ability to generalize the results of this study to other populations. STUDY FUNDING/COMPETING INTEREST(S) This study was not funded, and there are no conflicts of interest. TRIAL REGISTRATION NUMBER n/a.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Ovarian response in three consecutive in vitro fertilization cycles.

OBJECTIVE This study was designed to assess the ovarian response in the same patient in consecutive IVF cycles. DESIGN Retrospective study. SETTING Assisted reproductive unit at a university hospital. PATIENT(S) One hundred ninety women who underwent three consecutive cycles of IVF. INTERVENTION(S) All women used a combination of pituitary desensitization and gonadotropin stimulation protocol and underwent oocyte retrieval. MAIN OUTCOME MEASURE(S) Number of follicles produced and number of oocytes retrieved. RESULT(S) There were no significant differences in the number of follicles produced, number of oocytes retrieved, and number of embryos created by the same woman among the three cycles of treatment. CONCLUSION(S) Consistent ovarian response can be achieved during the first three consecutive IVF cycles.

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes

OBJECTIVE To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. DESIGN Retrospective analysis. SETTING University-based IVF center. PATIENT(S) Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. MAIN OUTCOME MEASURE(S) Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. RESULT(S) The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. CONCLUSION(S) This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist.

OBJECTIVE To determine factors predicting cycle success after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in high-risk patients undergoing controlled ovarian stimulation with a gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist to induce oocyte maturation. DESIGN Retrospective cohort study. SETTING University-based tertiary fertility center. PATIENT(S) Women who underwent a GnRH antagonist protocol during IVF-ICSI cycles and received a GnRH agonist for oocyte maturation. INTERVENTION(S) GnRH-agonist trigger. MAIN OUTCOME MEASURE(S) Clinical and ongoing pregnancy rates and any occurrence of ovarian hyperstimulation syndrome (OHSS). RESULT(S) The serum luteinizing hormone (LH) level on the day of trigger of oocyte maturation was the single most important predictor of clinical pregnancy. Patients with a peak estradiol (E(2)) level ≥4,000 pg/mL also had statistically significant higher serum LH on the day of the GnRH-agonist trigger and had a higher clinical pregnancy rate compared with those with a peak E(2) level <4,000 pg/mL, although the two groups had comparable numbers of oocytes retrieved. No patients developed OHSS. CONCLUSION(S) Serum LH and E(2) levels ≥4,000 pg/mL on the day of the GnRH-agonist trigger are important predictors of success in patients at high risk of OHSS development. As none of the patients in this high-risk population developed OHSS, the GnRH-agonist trigger is effective in the prevention of this iatrogenic complication.