Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer

Saito, Natsuho; Yamashita, Yoshiki; Higuchi, Yoko; Hayashi, Akira; Yamaguchi, Yoko; Yamamoto, Hitoshi; Kawabe, Sachiko; Kamada, M.; Ohmichi, Masahide

doi:10.1007/s12522-013-0147-z

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Recently, the Cochrane Collaboration group reported moderate evidence of increased ongoing pregnancy rates after LH-containing gonadotrophin stimulation when compared to FSH-only cycles ( Mochtar et al , 2017 ). Mitochondrial gene expression data in granulosa cells support these findings: Saito et al (2013) demonstrated higher gene expression ratios and improved rates of high-quality embryos in women undergoing LH-containing stimulation with hMG when compared to a recombinant FSH regimen. While younger women may still be able to cope with such unfavorable conditions, older women, with an already somewhat compromised follicular competence, will not.…”

Section: Discussionmentioning

confidence: 63%

The ovarian sensitivity index is predictive of live birth chances after IVF in infertile patients

Weghofer

Barad

Darmon

et al. 2020

Human Reproduction Open

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STUDY QUESTION Does the ovarian sensitivity index (OSI) predict embryo quality, pregnancy and live birth in patients undergoing FSH/hMG stimulation for IVF? SUMMARY ANSWER The OSI is predictive of pregnancy and live birth in older women with a more unfavorable prognosis undergoing FSH/hMG stimulation for IVF. WHAT IS KNOWN ALREADY The OSI was previously reported to reflect gonadotrophin requirements among high, normal and poor responders and to predict pregnancy potential in younger patients undergoing ovarian stimulation with FSH. STUDY DESIGN, SIZE, DURATION A retrospective cohort study that included 1282 women undergoing IVF with FSH/hMG stimulation was carried out between January 2010 and December 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS We evaluated 1282 women who underwent fertility treatment with FSH/hMG stimulation and oocyte retrieval at an academically affiliated private fertility center. OSI was calculated as (oocytes ×1000)/total gonadotrophin dose and grouped into two classes based on a receiver operating characteristic (ROC) curve analysis of a randomly selected development sample comprising one-third of the cycles. The remaining cycles comprised the validation group. ROC curves were also used to compare the predictive value of OSI to that of baseline FSH and anti-Müllerian hormone (AMH). Logistic regression models evaluated the effect of high (OSI >0.83) and low (OSI ≤0.83) on clinical pregnancy and live birth in the validation group. Models were adjusted for female age, baseline FSH, AMH and oocyte yield and gonadotrophin dose. MAIN RESULTS AND THE ROLE OF CHANCE Women presented with a mean ±SD age of 38.6 ± 5.4 years and showed median AMH levels of 0.65 (95% CI 0.61–0.74) ng/ml. They received 5145 ± 2477 IU of gonadotrophins and produced a median 5.2 (95% CI 5.0–5.5) oocytes. Pregnancy and live birth rates per oocyte retrieval for all women were 20.6% and 15.8%, respectively. Patients with higher OSI (less gonadotrophin required per oocyte retrieved) produced significantly more high-quality embryos than patients with low OSI (3.5 (95% CI 3.2–3.8) versus 0.6 (95% CI 0.5–0.7) (P = 0.0001)) and demonstrated higher pregnancy (23.2% versus 9.7%) and live birth rates (8.8% versus 5.3%) than their counterparts (P = 0.0001 and P = 0.0001, respectively). After adjustments for age, baseline AMH and FSH, total gonadotrophin dosage and oocyte yield, an OSI >0.83 was associated with greater odds of pregnancy (odds ratio 2.12, 95% CI 1.30–3.45, P < 0.003) and live birth (odds ratio 1.91, 95% CI 1.07–3.41, P < 0.028). LIMITATIONS, REASONS FOR CAUTION The results may not be applicable to women with excellent pregnancy potential or FSH-only stimulation. WIDER IMPLICATIONS OF THE FINDINGS The predictive capacity of OSI for embryo quality, pregnancy and live birth, which is independent of AMH or FSH, may help in counseling patients about their pregnancy potential and live birth chances. STUDY FUNDING/COMPETING INTEREST(S) Intramural funding from the Center for Human Reproduction and the Foundation for Reproductive Medicine. A.W., V.A.K., D.F.A., D.H.B. and N.G. have received research grant support, travel funds and speaker honoraria from various pharmaceutical and medical device companies: none, however, related to the topic presented here. D.H.B. and N.G. are listed as inventors on already awarded and still pending US patents, claiming beneficial effects on diminished ovarian reserve and embryo ploidy from dehydroepiandrosterone supplementation. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionmentioning

confidence: 63%

The ovarian sensitivity index is predictive of live birth chances after IVF in infertile patients

Weghofer

Barad

Darmon

et al. 2020

Human Reproduction Open

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“…High total FSH dosage in women ≤38 years old has been shown to negatively impact subsequent embryo quality and blastocyst formation rate [26]. In contrast, the FSH dosage had no impact on the mitochondrial expression of a polycistronic RNA transcript in GCs of IVF patients [27].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial metabolic substrate utilization in granulosa cells reflects body mass index and total follicle stimulating hormone dosage in in vitro fertilization patients

Kordus

Hossain

Malter

et al. 2020

J Assist Reprod Genet

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Purpose To utilize a novel mitochondrial function assay with pooled granulosa cells to determine whether mitochondrial function would differ by patient demographics and embryo development. Methods This was a prospective pilot study in a hospital-based assisted reproductive program and public university. Mitochondrial metabolic substrate utilization was assessed in pooled granulosa cells from 40 women undergoing in vitro fertilization during 2018 and 2019. Results Assessment of mitochondrial substrate metabolism in pooled granulosa cells revealed higher citric acid, L-malic acid, and octanoyl-L-carnitine utilization with higher body mass index (BMI). Utilization of citric acid, cis-aconitic acid, D-alphaketo-glutaric acid, L-glutamine, and alanine plus glycine was significantly lower as total dosage of FSH administered increased. Utilization of glycogen was significantly higher in patients with a higher percentage of fertilized oocytes. D-alpha-keto-glutaric acid utilization was significantly lower in patients with a higher percentage of good 8-cell embryos. L-glutamine utilization was significantly lower, with a higher percentage of blastocyst formation. Mitochondrial metabolic scores (MMS), which reflect overall mitochondrial activity of the granulosa pool, were significantly higher in patients with higher BMI and with greater numbers of mature oocytes retrieved. MMS in granulosa decreased as total FSH dose administered increased. Conclusions Granulosa cell utilization of substrates feeding into the citric acid cycle changed with total FSH dosage and BMI. Fertilization rate, 8-cell embryo quality, and blastocyst formation also associated with different energy substrate usage. Mitochondrial substrate utilization by granulosa cells from individual follicles could be further developed into a useful diagnostic tool.

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Ovarian stimulation protocols: impact on oocyte and endometrial quality and function

Harvey,

Willson,

Surrey

et al. 2024

Fertility and Sterility

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Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer

Cited by 3 publications

References 40 publications

The ovarian sensitivity index is predictive of live birth chances after IVF in infertile patients

The ovarian sensitivity index is predictive of live birth chances after IVF in infertile patients

Mitochondrial metabolic substrate utilization in granulosa cells reflects body mass index and total follicle stimulating hormone dosage in in vitro fertilization patients

Ovarian stimulation protocols: impact on oocyte and endometrial quality and function

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