SAY NO to mild ovarian stimulation for all poor responders: it is time to realize that not all poor responders are the same

2020 ◽  
Vol 35 (9) ◽  
pp. 1964-1971 ◽  
Author(s):  
N P Polyzos ◽  
B Popovic-Todorovic
Keyword(s):  
Ovarian Stimulation ◽  
Ovarian Response ◽  
Poor Responder ◽  
Treatment Modalities ◽  
Poor Responders ◽  
Mild Ovarian Stimulation ◽  
Mild Stimulation ◽  
Current Article ◽  
Poor Ovarian Responders ◽  
Intense Stimulation

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.

scholarly journals Natural Cycle Results in Lower Implantation Failure than Ovarian Stimulation in Advanced-Age Poor Responders Undergoing IVF: Fertility Outcomes from 585 Patients

2021 ◽  
Author(s):  
Maria Paola De Marco ◽  
Giulia Montanari ◽  
Ilary Ruscito ◽  
Annalise Giallonardo ◽  
Filippo Maria Ubaldi ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Embryo Implantation ◽  
Implantation Rate ◽  
Poor Responder ◽  
Advanced Age ◽  
Poor Responders ◽  
Natural Cycle ◽  
Significant Difference ◽  
Over 40 Years

AbstractTo compare pregnancy rate and implantation rate in poor responder women, aged over 40 years, who underwent natural cycle versus conventional ovarian stimulation. This is a retrospective single-center cohort study conducted at the GENERA IVF program, Rome, Italy, between September 2012 and December 2018, including only poor responder patients, according to Bologna criteria, of advanced age, who underwent IVF treatment through Natural Cycle or conventional ovarian stimulation. Between September 2012 and December 2018, 585 patients were included within the study. Two hundred thirty patients underwent natural cycle and 355 underwent conventional ovarian stimulation. In natural cycle group, both pregnancy rate per cycle (6.25 vs 12.89%, respectively, p = 0.0001) and pregnancy rate per patient101 with at least one embryo-transfer (18.85 vs 28.11% respectively, p = 0.025) resulted significant reduced. Pregnancy rate per patient managed with conventional ovarian stimulation resulted not significantly different compared with natural cycle (19.72 vs 15.65% respectively, p = 0.228), but embryo implantation rate was significantly higher in patients who underwent natural cycle rather than patient subjected to conventional ovarian stimulation (13 vs 8.28% respectively, p = 0.0468). No significant difference could be detected among the two groups in terms of abortion rate (p = 0.2915) or live birth pregnancy (p = 0.2281). Natural cycle seems to be a valid treatment in patients over 40 years and with a low ovarian reserve, as an alternative to conventional ovarian stimulation.

scholarly journals Morphokinetic Characteristics and Developmental Potential of In Vitro Cultured Embryos from Natural Cycles in Patients with Poor Ovarian Response

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
N. Hojnik ◽  
V. Vlaisavljević ◽  
B. Kovačič
Keyword(s):  
Implantation Rate ◽  
Ovarian Response ◽  
Time Lapse ◽  
Poor Responder ◽  
Poor Responders ◽  
Poor Ovarian Response ◽  
Developmental Potential ◽  
The Impact ◽  
Natural Cycles

Background. Patients with poor ovarian response to ovarian hyperstimulation represent an interesting group for studying the impact of embryo cleavage irregularities on clinical outcome since all embryos, regardless of their quality, are usually transferred to the uterus. The aim of our study was to follow the morphokinetics of fertilized oocytes from natural cycles in poor responders. Methods. Zygotes from 53 cycles were cultured in vitro for 3 days. The morphokinetics of their development and transfer outcomes were retrospectively analyzed for the normally and irregularly cleaved embryos. Results. Of all embryos, 30.2% had single and 20.8% multiple cleavage irregularities with the following prevalence: developmental arrest 30.2%, direct cleavage to more than two cells 24.5%, chaotic cleavage 13.2%, and reverse cleavage 11.3%. These embryos had longer pronuclear phases, first cytokinesis, second embryo cell cycles, and less synchronized divisions. The transfer of normally developing embryos resulted in an implantation rate of 30.8% and a delivery rate of 23.1%, but irregularly cleaved embryos did not implant. Conclusions. The use of time-lapse microscopy in poor responder patients identified embryos with cleavage abnormalities that are related with no or extremely low implantation potential. Gained information about embryo quality is important for counselling patients about their expectations.

scholarly journals Whether poor responses have worse perinatal prognosis (retrospective analysis of assisted reproductive technologies cycle)

2018 ◽  
Vol 22 (3) ◽  
pp. 503-508
Author(s):  
G.V. Strelko
Keyword(s):  
Gestational Diabetes ◽  
Ovarian Stimulation ◽  
Preterm Labor ◽  
Perinatal Outcomes ◽  
Ovarian Response ◽  
Control Group ◽  
Poor Responders ◽  
Poor Ovarian Response ◽  
Normal Response ◽  
Significant Difference

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.

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 ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Multiple Dose ◽  
Paired Comparison ◽  
Ovarian Response ◽  
Clinical Pregnancy ◽  
Poor Responders ◽  
Ivf Outcomes ◽  
Oocyte Yield ◽  
Subsequent Cycle ◽  
Estradiol Levels

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.

Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders

2020 ◽  
Author(s):  
R Moffat ◽  
C Hansali ◽  
A Schoetzau ◽  
A Ahler ◽  
U Gobrecht ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Primary Outcome ◽  
Clomiphene Citrate ◽  
Ovarian Response ◽  
Serum Levels ◽  
Follicular Phase ◽  
Poor Responders ◽  
Starting Dose ◽  
Early Follicular Phase ◽  
Randomised Controlled

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

scholarly journals Accumulation of oocytes and/or embryos by vitrification: a new strategy for managing poor responder patients undergoing pre implantation diagnosis

F1000Research ◽  
2014 ◽  
Vol 2 ◽  
pp. 240 ◽  
Author(s):  
Alexia Chatziparasidou ◽  
Martine Nijs ◽  
Martha Moisidou ◽  
Oraiopoulou Chara ◽  
Christina Ioakeimidou ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Ovarian Stimulation ◽  
Genetic Diagnosis ◽  
Poor Responder ◽  
Optimal Number ◽  
Poor Responders ◽  
Healthy Pregnancy ◽  
Group A ◽  
Low Responder ◽  
Group B

Background: Low (or poor) responder patients are women who require large doses of stimulation medications and produce less than an optimal number of oocytes during IVF cycles. Low responder patients produce few oocytes and embryos, which significantly reduces their chances for success in a preimplantation genetic diagnosis (PGD) cycle. Accumulation of vitrified oocytes or embryos before the actual PGD cycle is a possible strategy that might increase patient’s chances for a healthy pregnancy.Aim of the study: This retrospective study evaluates the efficacy of a PGD program in low responder patients after repeated ovarian stimulation cycles with cumulative vitrification of oocytes and embryos.Methods: Over a period of 30 months, 13 patients entering the PGD program were identified as poor responders after their first ovarian stimulation. These patients started a PGD cycle for one of the following indications: history of recurrent implantation failure (n=1), cystic fibrosis (n=1), X-linked microtubular myopathy (n=1), recurrent miscarriages (n=5), Duchene muscular dystrophy (n=1), chromosomal translocation (n=1) and high sperm aneuploidy (n=1).  After multiple ovarian hormonal stimulations patients had either all mature oocytes (Group A; 3 patients) or all of their day 2 embryos vitrified (group B; 10 patients). Mean total number of oocyte collections per patient was 2.3 (range: 2 - 5 cycles).Results: In the actual PGD cycle, all vitrified oocytes from group A patients were warmed and underwent intra cytoplasmic sperm injection (ICSI) followed by culture up to day 3. For group B patients all vitrified day 2 embryos were warmed and cultured overnight. On day 3 of culture, all embryos from Group A and B had blastomere biopsy followed by genetic analysis. In group A, 20 embryos were found suitable for biopsy and genetic analysis; at least one healthy embryo was available for transfer for each patient.  For group B, 72 embryos in total were available for biopsy and PGD.  All patients, except one, had at least one healthy day 5 embryo for transfer (mean number of 2.1 embryos per transfer). Nine patients had a clinical pregnancy; 7 patients delivered a healthy baby.Conclusion: Low responder patients entering a PGD program might increase their chances for a healthy pregnancy by repeat ovarian stimulation in combination with cumulative oocyte or embryo vitrification.

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