Aromatase Inhibitors for IVF Poor Responders

Objective To evaluate whether letrozole enhanced follicular recruitment, embryo numbers, and pregnancy rates in poor responders undergoing IVF. Methods We reviewed all IVF cycles between January 2002 and September 2003 using letrozole at Stanford University Medical Center. The entry criteria were the requirement of at least 450 IU/d of injectable gonadotropins in a prior failed cycle, which was used as a control. Results A total of 27 charts were reviewed revealing information on 54 cycles. The number of oocytes retrieved, fertilization, embryo quality and embryos transferred yielded no statistical significance, although there appeared to be a trend toward higher numbers of each in the letrozole group. The clinical pregnancy rate was 9/27 （33.3%, P〈0.001） with a viable pregnancy rate of 7/27 （25.9%, P=0. 002） in the Ietrozole cycle. Conclusion Our study is one of the first to evaluate letrozole with in vitro fertilization. Although this study showed no difference in number of oocytes or embryos, 25.9% of these ＂poor responding＂ patients achieved a pregnancy after a failed cycle at our center.

Preliminary Results of DHEA in Poor Responders in IVF

Objective: Dehydroepiandrosterone (DHEA) has been previously reported to improve ovarian response in IVF for poor responders. Its effect remains uncertain. The purpose of this study was to evaluate the effect of DHEA given during two years in our unit, in order to build hypothesis for a future randomized controlled trial. Design: Cohort of exposed and non-exposed DHEA study. Patient(s): 224 patients with AMH under 1.6 ng/ml undergoing IVF with a short antagonist protocol adding FSH and LH rec were enrolled for 327 IVF cycles. 176 patients had been treated with DHEA before IVF, and 151 had not. Intervention(s): None. Main Outcome Measure(s): Cancellation cycle rate, amount of gonadotrophins used, estradiol level on day six of stimulation, number of oocytes retrieved, metaphase II oocytes, blastocysts and frozen embryos, clinical pregnancy rate and miscarriage rate. Results: The cancellation rate was significantly higher in the group without DHEA (29.8% versus 13.1%, p = 0.002). The amount of gonadotrophins used for stimulation, the estradiol level on day six of stimulation, the number of oocytes retrieved, metaphase II oocytes, blastocysts, frozen embryos and miscarriage rate were not different in both groups. The clinical pregnancy rate per included patient in the DHEA group was 17.1% versus 8.6% in the non-treated group (p = 0.02). Conclusion: DHEA appears to improve clinical pregnancy rate by decreasing the cancellation rate.

Cumulative Live Birth Rate after Three Ovarian Stimulation IVF Cycles for Poor Ovarian Responders According to the Bologna Criteria

Summary： This study explored the cumulative live birth rate after three ovarian stimulation in vitro fer- tilization （IVF） cycles for poor ovarian responders according to the Bologna criteria. In this retrospec- tive cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cu- mulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%--24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and 〉40 years, re- spectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth, rate after three ovarian stimulation IVF cycles, especially poor responders aged 〈40 years.

Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective:This study aimed to compare the efficacy of clomiphene citrate(CC)with human menopausal gonadotropin(hMG)and that of medroxyprogesterone acetate(MPA)with hMG in poor responders defined according to the Bologna criteria.Methods:The data of patients with poor ovarian response(POR)according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed.All participants received either CC+hMG or the progesterone-primed ovarian stimulation protocol(PPOS)protocol.Results:A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study.The incidence of spontaneous luteinizing hormone(LH)surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC+HMG group(0.04%vs.3.49%and 4.26±3.59 vs.9.38±6.92 mIU/mL,respectively,P<0.05);however,the incidence of premature ovulation was similar between the two groups.The number of viable embryos harvested was not statistically different between the two groups(1.7±1.1 vs.1.5±0.8,P=0.06).The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC+hMG group(908.7±556.6 vs.177.9±214.5 IU and 6.0±3.4 vs.1.2±1.5 days,respectively,P<0.05).However,the number of oocytes retrieved,number of metaphase II oocytes,and fertilization rate were comparable between the two groups.Conclusions:The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.

Predictive factors for clinical pregnancies of poor responders diagnosed according to the Bologna criteria in ovarian stimulation in vitro fertilization(IVF)

Objective To explore the predictive factors for clinical pregnancies of poor responders diagnosed according to the Bologna criteria in ovarian stimulation in vitro fertilization （IVF） .Methods The present study included 392 poor responders diagnosed according to the Bologna criteria （392 first poor response cycles and 247 subsequent conventional stimulation cycles） in our IVF center. Binary Logistic regression analysis was used to study the association between possible predictive factors and clinical pregnancy of poor responders in ovarian stimulation IVF.Results The significant predictive factors for clinical pregnancies of poor responders in ovarian stimulation IVF were female age, number of embryos transferred and ovarian stimulation protocol. Female age had the best predictive value for clinical pregnancy of poor ovarian responders.Conclusion Poor responders should be encouraged to attempt Jurther ovarian stimulation IVF treatment as soon as possible because the pregnancy rate decreases with advancing female age. Growth hormone supplementation, intracytoplasmic sperm injection （ICSI） procedure or assisted hatching seem not be able to prominently improve the pregnancy outcomes of poor responders diagnosed according to the Bologna criteria in ovarian stimulation IVF.

Modified super-long down-regulation protocol improves fertilization and pregnancy in patients with poor ovarian responses

Background The successful end-point of in vitro fertilization （IVF） treatment is for a woman to give live birth. This outcome is based on various factors including adequate number of retrieved eggs. Failure to recruit adequate follicles, from which the eggs are retrieved, is called a ＂poor response＂. How to improve the clinical pregnancy rates of poor responders was one of the tough problems for IVF. Methods The study involved 51 patients who responded poorly to high dose gonadotropin treatment in their previous cycles at our reproductive center, between April 2010 and February 2012. The previous cycle （group A） received routine long protocol; the subsequent cycle （group B） received modified super-long down-regulation protocol. The primary outcome of the study was the number of oocytes fertilized. The increase in the pregnancy rate was the secondary outcome. Differences between the groups were assessed by using Student＇s t test and Z2 test where appropriate. Results The patients＇ average age was （36.64±3.85） years. The mean duration of ovarian stimulation cycles of the group A patients was longer than those of the group B patients. The total dose of follicle-stimulating hormone （FSH） was significantly lower in the subsequent cycle. The peak value of serum estradiol on human chorionic gonadotrophin （hCG） day was lower in group A as compared with group B. The number of metaphase II oocytes recovered was significantly higher in group B. The cleavage rate in group A was significantly lower than in group B, 49 patients in group B reached embryo transfer stage, while 46 patients in group A reached this stage. Patients in group B received significantly more embryos per transfer as compared with group A. More pregnancies and more clinical pregnancies with fetal heart activity were achieved in group B. Conclusions This comparative trial shows that poor responder women undergoing repeated assisted reproduction treatment using modified super-long down-regulation protocol achieve more oocytes, leading to higher fertilization rate, compared to women receiving routine long protocol. Our study also showed that clinical pregnancy rate was significantly improved.