scholarly journals Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor and sub optimal responders?

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Moran Shapira ◽  
Raoul Orvieto ◽  
Oshrit Lebovitz ◽  
Ravit Nahum ◽  
Adva Aizer ◽  
...  

Abstract Background Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course. Methods We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed. Results Twenty-four patients were included. Mean patients’ age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p < 0.05). Number of retrieved oocytes (3.29 ± 2.15 vs 6.46 ± 3.20, p < 0.05), MII-oocytes (2.47 ± 1.65 vs 5.59 ± 3.20, p < 0.05), 2PN-embryos (1.78 ± 1.50, 4.04 ± 2.74, p < 0.05) and top-quality embryos (0.91 ± 0.97 vs. 2.35 ± 1.66, p < 0.05) were significantly higher in the gonadotropins-letrozole cycles. Clinical pregnancy rate in gonadotropins-letrozole cycles was 31.5%. Conclusion Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Bekzatova ◽  
M Shishimorova

Abstract Study question The aim of this study is to determine whether repetitive natural cycles (Strategy A) or oocyte accumulation (Strategy B) is a more effective strategy. Summary answer There was no statistical difference between the strategies however, the number of attempts for successful outcome with strategy A was lower than in strategy B. What is known already For populations with poor ovarian response natural cycles (NC) or modified natural cycles (mNC) with minimal stimulation have been implemented as a preferable option as opposed to conventional ovarian stimulation. Due to the development of advanced vitrification techniques, the accumulation of oocytes has become available. Previous studies (2011, 2013, 2019) suggest that accumulation of oocytes could be a successful alternative to repetitive natural cycles for poor responders aged ≥35 years, showing higher clinical pregnancy rates. Moreover, the embryo-transfer cancellation and miscarriage rate were significantly lower in the oocyte accumulation strategy. Study design, size, duration Present retrospective cohort study included a selection of patients with POR treated from 2019–2020, which were divided into 2 strategies. Strategy A included 324 natural cycles or modified natural cycles with successful oocyte retrievals (Female mean age: 36.3 years). The strategy B consisted of 46 cycles with thawed oocytes that were accumulated through cryopreservation in several attempts (average n = 2,3) prior in NC or mNC (Female mean age: 37.6 years). Participants/materials, setting, methods POR was defined by following criteria: 1) advanced maternal age (≥35 years) or; 2) previous POR (≤3 oocytes with a conventional ovarian stimulation protocol); 3) abnormal ovarian reserve test; The vitrification of the oocytes was performed using Kuwayama method (Cryotech®, Japan), while thawing was performed using Cryotop method (Kitazato®, Japan). Prior to fertilization, oocytes were cultured for 2 hours in IVF medium (Origio®, Denmark). The unsuccessful transvaginal oocyte retrievals (TVOR) were excluded from both strategies. Main results and the role of chance The clinical pregnancy rate per started cycle and per transfer in Strategy A vs Strategy B were 15,4% vs 15,2% and 28.08% vs 20%, respectively. Strategy A seemed to achieve higher rates; however, the difference was not statistically significant (Student’s t-test, p &lt; 0.05). Throughout all TVORs the rate of successful retrieval was 71.7%. The embryo-transfer cancellation rates in Strategy A vs Strategy B were 38,2% vs 8,69%, respectively. With strategy A the average amount of attempts for successful clinical pregnancy was 1.86. With strategy B the average amount of cryopreservations for oocyte accumulation was 2.3. Limitations, reasons for caution The number of patients in strategy B was significantly lower than in strategy A. Larger study with an increased number of samples is necessary to confirm the results. In addition calculation of cost-effectiveness in each strategy. The unsuccessful TVORs were excluded from both strategies, which significantly affects the statistical rates. Wider implications of the findings: This study might help in developing and selecting more appropriate strategies for women with POR. The findings might help to determine the amount of time and attempts required for a successful outcome for patients aged ≥35. It can also be helpful in regulating the financial part of artificial reproductive technology. Trial registration number N/A


2019 ◽  
Vol 32 (1) ◽  
pp. 25
Author(s):  
Mariana Carlos Alves ◽  
Andreia Leitão Marques ◽  
Helena Barros Leite ◽  
Ana Paula Sousa ◽  
Teresa Almeida-Santos

Introduction: Medically assisted reproduction in natural cycle has been investigated, especially in women with poor response to conventional ovarian stimulation, with endometrial receptivity improvement, lower cost and possibility of successive cycles. The disadvantages are: lower profitability per treatment cycle and higher cancellation rate. The aim of this study was to determine the rate of clinical pregnancy in infertile women subjected to medically assisted reproduction in natural cycle.Material and Methods: Retrospective study of 149 medically assisted reproduction without ovarian stimulation of 50 infertile women, between January/2011 and October/2014.Results: The mean age of women undergoing medically assisted reproduction in natural cycle was 36.1 years. Approximately half (46.0%) of the cycles were performed in poor responders. On the day of ovulation trigger, the mean diameter of the follicle was 17.5 mm. Twenty-three cycles (15.4%) were canceled prior to ovulation trigger. In 8 cycles (5.3%), ovulation occurred between ovulation trigger and oocyte retrieval. In the majority of cycles (n = 118; 79.2%) oocyte retrieval was executed, a medically assisted reproduction technique was performed in 71 (47.6%), mostly intracytoplasmic injection. The overall fertilization rate was 77.5%. In 40 cycles (26.8%) there was embryo transfer. The implantation rate and the clinical pregnancy rate by embryo transfer was 35.0% and 25.0%, respectively. Most pregnancies occurred in poor responders, according to Bologna criteria.Discussion: Although the pregnancy rate per cycle started was 6.7%, the rate of clinical pregnancy per embryo transfer is quite satisfactory, being a group of women with unfavorable responses in previous treatments. The relatively high rates of cycle cancellation are mitigated by the greater simplicity and lower cost of these cycles.Conclusion: The results obtained in this study demonstrate that Medically Assisted Reproduction in natural cycle may be an alternative treatment for ovarian stimulation in patients with poor prognosis, whose only alternative would be oocyte donation.


2020 ◽  
Vol 35 (9) ◽  
pp. 1964-1971 ◽  
Author(s):  
N P Polyzos ◽  
B Popovic-Todorovic

ABSTRACT Over the last 25 years, a vast body of literature has been published evaluating different treatment modalities for the management of poor ovarian responders. Despite the evidence that maximizing ovarian response can improve the chances of live born babies in poor responders, there are still voices suggesting that all poor responders are the same, irrespective of their age and their actual ovarian reserve. This has resulted in the suggestion of adopting a mild ovarian stimulation approach for all poor responders, based on the results of several trials which failed to identity differences when comparing mild and more intense stimulation in predicted poor responders. The current article analyzes in detail these studies and discusses the shortcomings in terms of type of population included, outcomes and settings performed, which may actually be responsible for the belief that only mild stimulation should be used. In the era of individualization in medicine, it must be realized that there are subgroups of predicted poor responders who will benefit from an individual rather than ‘one fits all’ mild stimulation approach and thus we should provide the same standard of treatment for all our poor responder patients.


2018 ◽  
Vol 22 (3) ◽  
pp. 503-508
Author(s):  
G.V. Strelko

The prevalence of poor ovarian response is 5.6–35.1% in women undergoing controlled ovarian stimulation in ART cycles. The frequency of delivery of poor responders after ART is on average from 9.9% to 23.8%. In clinical practice, the vast majority of poor responders are older women, which may have an effect on perinatal outcomes, respectively. Although numerous studies have reported that the fertility rate after ART in women of this age group is quite low, data on perinatal outcomes in this group of women is limited. Therefore, the aim of our study was to retrospectively analyze and compare perinatal outcomes in women with poor ovarian response to stimulation compared to control group (normal response to stimulation) in assisted reproductive technology programs. 278 women with infertility with a reduced response to stimulation (poor responders), who were the main group, were screened. Indications for the inclusion of women in the main group were the presence of at least two of the following criteria for a poor ovarian response according to the 2011 Bologna criteria and 93 infertile patients with a normal ovarian response to stimulation of the control group. Subsequently, retrospective study of perinatal effects such as preterm labor, low birth weight, gestational diabetes, preeclampsia in 50 women with infertility with reduced response to stimulation and 37 controls with normal response to stimulation in which pregnancy was diagnosed was performed. Variational-statistical processing of the results of the study was performed using the program “Statistica 6.0”. The study demonstrated a significantly lower pregnancy rate in poor responders compared with women from the control group — 50 (17.9%) vs. 37 (39.8%), respectively. Perinatal outcome were similar only to the statistically significant difference in the percentage of spontaneous abortions before 12 weeks of gestation — 9 (18%) vs. 4 (10.8%), respectively, in groups with no significant difference in the preterm labor frequency — 10 (20.8%) and 6 (18.1%) of the low weight of the child at birth — 9 (18.7%) versus 5 (15.1%), respectively, in poor responders patients and in women with normal ovarian response. The frequency of complications such as gestational diabetes and high blood pressure were not significantly different in both clinical groups — 3 (6.25%) versus 2 (6.1%) and 5 (10.4%) versus 3 (9.1%) respectively. Thus, he poor responders in ART programs have a significantly lower pregnancy rate and a higher incidence of pregnancy loss up to 12 weeks compared with women who had a normal response to ovarian stimulation without a significant difference in the rates of various complications of pregnancy and perinatal outcomes. Wide randomized multicentric trials are needed to find out the causal relationships with regard to the effect on pregnancy, miscarriage, perinatal effects of controlled ovarian stimulation regimens, embryotransfers in fresh or cryo cycles etc.


Zygote ◽  
2019 ◽  
Vol 27 (05) ◽  
pp. 347-349 ◽  
Author(s):  
L.T. Paul ◽  
O. Atilan ◽  
P. Tulay

SummaryThe aim of this study was to investigate if there is an adverse effect of multiple controlled ovarian stimulation (COS) on the maturity of oocytes (MI and MII), fertilization rate, embryo developmental qualities and clinical pregnancy rates in donation cycles. In total, 65 patients undergoing oocyte donation cycles multiple times were included in this study. Patients were grouped as group A that consisted of donors with ≤2 stimulation cycles while B consisted of donors with ≥3 stimulation cycles; and group C included donors who had ≤15 oocytes, while group D had donors with ≥16 oocytes. Numbers of oocytes obtained, MI and MII oocytes, fertilization, embryo quality and clinical pregnancy outcomes were compared. Significant statistical differences were observed in total number of oocytes obtained, maturity of oocytes (MI and MII), fertilization rate, embryo qualities and clinical pregnancy outcomes of donors in groups A–D. Donors with ≤2 ovarian stimulation cycles had lower numbers of immature oocytes than donors with three or more stimulation cycles. However, donors with ≥3 stimulation cycles had higher numbers of mature oocytes, zygotes, with better day 3 embryo qualities and higher clinical pregnancy rates than donors with ≤2 stimulation cycles. Repeated COS does not seem to have any adverse effect on ovarian response to higher dose of artificial gonadotropin, as quality of oocytes collected and their embryological developmental potential were not affected by the number of successive stimulation cycles. The effect of multiple COS on the health of the oocyte donor needs to be assessed for future purpose.


2020 ◽  
Author(s):  
R Moffat ◽  
C Hansali ◽  
A Schoetzau ◽  
A Ahler ◽  
U Gobrecht ◽  
...  

Abstract STUDY QUESTION Does the gonadotropin (GN) starting dose and the addition of clomiphene citrate (CC) during the early follicular phase influence oocyte yield in poor responders undergoing ovarian stimulation for IVF treatment? SUMMARY ANSWER The number of retrieved oocytes was similar regardless of the starting dose of GN (150 versus 450 IU) with or without the addition of CC (100 mg from Day 3 to 7 versus placebo). WHAT IS KNOWN ALREADY ART in poor responders is a challenge for patients and clinicians. So far, randomised controlled studies addressing interventions have shown that neither the GN dose nor the addition of oral medication has any significant effect on the clinical outcome of ART in poor responders. There is limited knowledge about the effect of GN starting dose in combination with CC during the early follicular phase of ovarian stimulation on ovarian response markers and ART outcome. STUDY DESIGN, SIZE, DURATION This single-centre randomised double-blinded clinical trial was conducted from August 2013 until November 2017. Using the Bologna criteria, 220 of 2288 patients (9.6%) were identified as poor responders and 114 eligible participants underwent ovarian stimulation in a GnRH-antagonist protocol for ART. PARTICIPANTS/MATERIALS, SETTING, METHODS The participants were equally randomised to one of four treatment arms: Group A (n = 28) received 100 mg CC (Day 3–7) and a starting dose of 450 IU HMG, Group B (n = 29) received 100 mg CC and a starting dose of 150 IU HMG, Group C (n = 30) received placebo and a starting dose of 450 IU HMG and Group D (n = 27) received placebo and a starting dose of 150 IU HMG. Serum levels of FSH, LH, estradiol and progesterone were measured on Day 1 and 5 and on the day of ovulation induction. Available embryos were cultured up to the blastocyst stage and were always transferred in the same cycle. The primary outcome was the number of oocytes collected after ovarian stimulation. Other outcome measures were response to ovarian stimulation, embryo development and obstetrical outcome. MAIN RESULTS AND THE ROLE OF CHANCE All study participants (n = 114) fulfilled at least two of the Bologna criteria for poor responders. Median age of the study population was 38.5 years. There were 109 patients who underwent oocyte retrieval. The number of oocytes retrieved was similar among the groups (±SD; 95% confidence intervals); A: 2.85 (±0.48; 2.04–3.98), B: 4.32 (±0.59; 3.31–5.64); C: 3.33 (±0.52; 2.45–4.54); D: 3.22 (±0.51; 2.36–4.41); P overall = 0.246. However, ovarian stimulation with 150 IU plus CC resulted in a higher number of blastocysts compared to ovarian stimulation with 450 IU plus CC (±SD; 95% confidence intervals); A: 0.83 (±0.15; 0.58–1.2), B: 1.77 (±0.21; 1.42–2.22); P overall = 0.006. Mean FSH serum levels were lower in the groups with a starting dose of 150 IU. Adding CC did not affect mean serum FSH levels. There were no differences in estradiol concentrations among the groups. Endometrial thickness was lower in the groups receiving CC. The overall live birth rate (LBR) was 12.3%, and the cumulative LBR was 14.7%. LIMITATIONS, REASONS FOR CAUTION The trial was powered to detect differences in neither the number of blastocysts nor the LBR, which would be the preferable primary outcome of interventional trials in ART. WIDER IMPLICATIONS OF THE FINDINGS We found that ovarian stimulation with 150 IU gonadotrophin in combination with 100 mg CC produced more blastocysts. The effect of adding CC to GN on LBR in poor responders remains to be proven in randomised trials. High GN doses (450 IU) resulted in high FSH serum levels but increased neither the estradiol levels nor the number of retrieved oocytes, implying that granulosa cell function is not improved by high FSH serum levels. Lower starting doses of GN lead to a reduction of costs of medication. The small but significant difference in blastocyst formation and the lower FSH levels in the treatment groups receiving less GN may be an indication of better oocyte quality with higher developmental competence. STUDY FUNDING/COMPETING INTEREST(S) The costs for the HMG used for ovarian stimulation were provided by IBSA Switzerland. The study was also supported by the Repronatal Foundation, Basel, Switzerland. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER NCT01577472 TRIAL REGISTRATION DATE 13 April 2012 DATE OF FIRST PATIENT’S ENROLMENT August 2013


2002 ◽  
Vol 78 ◽  
pp. S49 ◽  
Author(s):  
William H Catherino ◽  
Mark Leondires ◽  
Jeffrey McKeeby ◽  
David Cruess ◽  
James H Segars ◽  
...  

2020 ◽  
Vol 68 (6) ◽  
pp. 37-46
Author(s):  
Alexandra I. Merkulova ◽  
Lyailya Kh. Dzhemlikhanova ◽  
Dariko A. Niauri ◽  
Alexander M. Gzgzyan ◽  
Igor Yu. Kogan ◽  
...  

Hypothesis/aims of study. Poor ovarian response is still considered one of the most challenging tasks in reproductive medicine. Poor responders have decreased circulating androgens during spontaneous cycles. Androgens are known to play an important role in follicular growth and development. Hence, the use of various androgens and androgen inhibitors in poor responders undergoing ovarian stimulation for IVF has been proposed to improve efficacy of treatment. This study was aimed to examine the efficacy of aromatase inhibitors and androgens in infertility treatment in patients with poor response. Study design, materials and methods. This prospective cohort-controlled clinical trial included 204 patients under 42 years of age with infertility and poor response to ovarian stimulation. In vitro fertilization treatment with an antagonist FSH/hMG protocol with letrozole (5 mg/day) was administered in the first group of patients (n = 26) during the first 5 days of stimulation. Patients of the second group (n = 38) were applied testosterone (25 mg/day) transdermally, starting from the 5th day of the menstrual cycle preceding controlled ovarian stimulation for in vitro fertilization. The third group of patients (n = 18) was administered dehydroepiandrosterone (100 mg/day) for 3 months prior to controlled ovarian stimulation for in vitro fertilization. Results. Improved response to FSH stimulation with letrozole co-treatment was evidenced, with parameters of stimulation efficacy and embryo development being better in the testosterone group. No significant improvement in ovarian response markers, ovarian response to gonadotrophin stimulation and in vitro fertilization outcomes were found in poor responders receiving pre-treatment dehydroepiandrosterone. Conclusion. Further studies are necessary to improve approaches of testosterone and aromatase inhibitors use in poor responders undergoing in vitro fertilization.


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