scholarly journals A direct action for GH in improvement of oocyte quality in poor-responder patients

Reproduction ◽  
2015 ◽  
Vol 149 (2) ◽  
pp. 147-154 ◽  
Author(s):  
B M Weall ◽  
S Al-Samerria ◽  
J Conceicao ◽  
J L Yovich ◽  
G Almahbobi

Declining female fecundity at later age and the increasing tendency for women to delay childbirth have lead to a drastic rise in the number of women seeking assisted reproductive technology. Many women fail to respond adequately to standard ovarian stimulation regimens, raising a significant therapeutic challenge. Recently, we have demonstrated that the administration of GH, as an adjunct to ovarian stimulation, has improved the clinical outcomes by enhancing the oocyte quality. However, the mechanism(s) by which GH facilitated this improvement is yet to be understood. This study aimed to determine these potential mechanism(s) through the use of immunofluorescent localisation of GH receptors (GHRs) on the human oocyte and unbiased computer-based quantification to assess and compare oocyte quality between women of varying ages, with or without GH treatment. This study demonstrates for the first time, the presence of GHRs on the human oocyte. The oocytes retrieved from older women showed significant decrease in the expression of GHRs and amount of functional mitochondria when compared with those from younger patients. More interestingly, when older patients were treated with GH, a significant increase in functional mitochondria was observed in their oocytes. We conclude that GH exerts a direct mode of action, enabling the improvement of oocyte quality observed in our previous study, via the upregulation of its own receptors and enhancement of mitochondrial activity. This result, together with recent observations, provides scientific evidence in support of the use of GH supplementation for the clinical management of poor ovarian response.

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Schachte. . Safrai ◽  
G Karavani ◽  
E Esh. Broder ◽  
E Levitase ◽  
T Wainstock ◽  
...  

Abstract Study question Does high ovarian response to controlled ovarian stimulation (COS) have a negative effect on oocyte quality? Summary answer High ovarian response is associated with reduced oocyte quality manifested as higher fraction of immature oocytes and higher rate of direct uneven cleavage (DUC) embryos. What is known already The literature regarding the effect of ovarian hyperstimulation on oocyte quality is limited and controversial. Results from several studies suggest that hyper response to controlled ovarian stimulation has a detrimental effect on oocyte and embryo quality, while others failed to confirm the existence of a direct toxic effect on oocyte and embryo quality. The association between temporal embryonal milestones and implantation rate has been previously demonstrated ,offering an additive tool by which oocyte quality, represented by embryo dynamics, can be evaluated. None of the aforementioned studies, however, used time lapse monitoring (TLM) system to evaluate oocyte and embryo quality. Study design, size, duration This study included a retrospective assessment of morphokinetic parameters performed by TLM from three university affiliated medical centers between January 2014 and December 2019. The developmental process and kinetics of 1863 embryos obtained from the study group, referred as the “ high ovarian response” (HOR) group, was compared to 4907 embryos from the control group - the “normal ovarian response” (NOR) group. Participants/materials, setting, methods The study included patients younger than 38 years who underwent COS with consecutive aspiration of either more than 15 oocytes (the HOR group) or 6–15 oocytes (the NOR group). A comparison was made between the groups regarding morphokinetic parameters, including the rate of embryos manifesting direct uneven cleavage (DUC) at first cleavage (DUC–1), as well as implantation and pregnancy rates. Logistic regression was conducted to assess the association between patients’ characteristics and implantation rate. Main results and the role of chance Oocyte maturation rate was significantly lower, and the DUC–1 embryos rate was significantly higher in the high ovarian response group compared to the normal ovarian response group (56.5% Vs 90.0%, p < 0.001 and 16.2% Vs 12.0%, p = <0.001; respectively). Following the exclusion of DUC–1 embryos, embryos from the HOR and the NOR groups reached the consecutive morphokinetic milestones at a similar rate and demonstrated similar implantation and clinical pregnancy rates. In a multivariate analysis preformed, only maternal age was found to be predictive for implantation. Limitations, reasons for caution The groups were not homogenous in their basic characteristics. Important information regarding the maximal dose of GT obtained, previous IVF response and ovarian reserve testing was lacking Wider implications of the findings: Higher oocyte quantity might have an effect on oocyte quality manifested as higher fraction of incompetent oocytes and higher rate of DUC–1 embryos. Once beyond the preliminary developmental stages, embryos from both groups reach the morphokinetic milestones at a similar rate and display similar implantation and pregnancy rates. Trial registration number Not applicable


2008 ◽  
Vol 90 ◽  
pp. S325
Author(s):  
R.d.C.S. Figueira ◽  
D.P.A.F. Braga ◽  
L.S. Francisco ◽  
C. Madaschi ◽  
A. Iaconelli ◽  
...  

Author(s):  
Bruno Ramalho de Carvalho ◽  
Geórgia Fontes Cintra ◽  
Taise Moura Franceschi ◽  
Íris de Oliveira Cabral ◽  
Leandro Santos de Araújo Resende ◽  
...  

AbstractWe report a case of ultrasound-guided ex vivo oocyte retrieval for fertility preservation in a woman with bilateral borderline ovarian tumor, for whom conventional transvaginal oocyte retrieval was deemed unsafe because of the increased risk of malignant cell spillage. Ovarian stimulation with gonadotropins was performed. Surgery was scheduled according to the ovarian response to exogenous gonadotropic stimulation; oophorectomized specimens were obtained by laparoscopy, and oocyte retrieval was performed ∼ 37 hours after the ovulatory trigger. The sum of 20 ovarian follicles were aspirated, and 16 oocytes were obtained. We performed vitrification of 12 metaphase II oocytes and 3 oocytes matured in vitro. Our result emphasizes the viability of ex vivo mature oocyte retrieval after controlled ovarian stimulation for those with high risk of malignant dissemination by conventional approach.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xinyue Zhang ◽  
Ting Feng ◽  
Jihong Yang ◽  
Yingying Hao ◽  
Suying Li ◽  
...  

Abstract Background Ovarian responsiveness to controlled ovarian stimulation is essential for a successful clinical outcome in assisted reproductive technology (ART) cycles. We aimed to find a suitable new ovulation stimulation protocol for poor ovarian response (POR) patients over 40 years old. Methods A retrospective analysis of 488 ART cycles was evaluated from January 2015 to June 2019. Comparisons were made between the flexible short protocol (FSP), routine short protocol and mild stimulation protocol. Results Compared with the routine short protocol, the FSP delayed the gonadotropin start time and reduced the total gonadotropin dose per stimulation cycle. At the same time, compared with the mild stimulation protocol, the FSP improved oocyte quality and embryo quality and improved embryo implantation potential after transfer. Furthermore, the use of the FSP reduced the probability of premature ovulation, as it inhibited the premature luteinizing hormone (LH) surge to a certain extent. Conclusions The FSP yielded better outcomes than other protocols for patients with POR over 40 years old in our study. However, further prospective studies are needed to provide more substantial evidence and to determine whether the FSP can be successful for both patients over 40 years group and younger POR patients.


Author(s):  
Maria Paola De Marco ◽  
Giulia Montanari ◽  
Ilary Ruscito ◽  
Annalise Giallonardo ◽  
Filippo Maria Ubaldi ◽  
...  

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.


2021 ◽  
Vol 15 ◽  
pp. 263349412110235
Author(s):  
Cristina Rodríguez-Varela ◽  
Sonia Herraiz ◽  
Elena Labarta

Poor ovarian responders exhibit a quantitative reduction in their follicular pool, and most cases are also associated with poor oocyte quality due to patient’s age, which leads to impaired in vitro fertilisation outcomes. In particular, poor oocyte quality has been related to mitochondrial dysfunction and/or low mitochondrial count as these organelles are crucial in many essential oocyte processes. Therefore, mitochondrial enrichment has been proposed as a potential therapy option in infertile patients to improve oocyte quality and subsequent in vitro fertilisation outcomes. Nowadays, different options are available for mitochondrial enrichment treatments that are encompassed in two main approaches: heterologous and autologous. In the heterologous approach, mitochondria come from an external source, which is an oocyte donor. These techniques include transferring either a portion of the donor’s oocyte cytoplasm to the recipient oocyte or nuclear material from the patient to the donor’s oocyte. In any case, this approach entails many ethical and safety concerns that mainly arise from the uncertain degree of mitochondrial heteroplasmy deriving from it. Thus the autologous approach is considered a suitable potential tool to improve oocyte quality by overcoming the heteroplasmy issue. Autologous mitochondrial transfer, however, has not yielded as many beneficial outcomes as initially expected. Proposed mitochondrial autologous sources include immature oocytes, granulosa cells, germline stem cells, and adipose-derived stem cells. Presently, it would seem that these autologous techniques do not improve clinical outcomes in human infertile patients. However, further trials still need to be performed to confirm these results. Besides these two main categories, new strategies have arisen for oocyte rejuvenation by improving patient’s own mitochondrial function and avoiding the unknown consequences of third-party genetic material. This is the case of antioxidants, which may enhance mitochondrial activity by counteracting and/or preventing oxidative stress damage. Among others, coenzyme-Q10 and melatonin have shown promising results in low-prognosis infertile patients, although further randomised clinical trials are still necessary.


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