CLINICAL ASSISTED REPRODUCTIVE TECHNOLOGY P-207 Tuesday, October 9, 2018 6:30 AM

A COMPARISON OF PRE-TREATMENT WITH AND

P-206 Tuesday, October 9, 2018 6:30 AM WITHOUT GNRH-AGONIST OR LETROZOLE IN
WOMEN WITH 2 FAILED EMBRYO TRANSFERS UN-
MITOCHONDRIAL TRANSFER FROM AUTOLOGOUS DERGOING A FROZEN CYCLE AND NO EVIDENCE
BONE MARROW MESENCHYMAL STEM CELLS IM- OF ENDOMETRIOSIS. M. H. Dahan, S. Tannus, S. Tan. McGill Uni-
PROVES OOCYTE QUALITY. R. Huang, C. Fang, versity, Montreal, QC, Canada.
L. Jia, G. Cao, Z. Zhang, X. Liang. Reproductive Medicine
Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, OBJECTIVE: Endometriosis is common in infertility populations,
China. affecting 30-50%. Endometriosis goes undiagnosed with laparoscopy in
infertility patients mostly abandoned. Treatment of endometriosis with
OBJECTIVE: Embryo quality ranks one of the most important predictors in depo-gonadotropin releasing hormone agonists (GnRH-ag), prior to embryos
determining the success of implantation, and, clinically, some patients experi- transfer improves outcomes. In non-fertility patients GnRh-ag and letrozole
ence repeated IVF failure because of refractory poor embryo quality due to is more effective at treating endometriosis than either alone. Our previous pi-
poor oocyte quality. Researches over the past decades leave no doubt that mito- lot study demonstrated improvement in outcomes in 38 subjects pre-treated
chondria are a hallmark of quality and developmental potential of human oo- with GnRh-ag-letrozole. This study was performed to confirm the finding in a
cytes, therefore, mitochondrial transfer (MIT), i.e, injecting mitochondria into large cohort.
oocyte, was proposed to improve oocyte quality. Recent studies showed that DESIGN: A prospective cohort study was performed on subjects who
mitochondrial transfer of mesenchymal stem cells (MSC) effectively protects failed two embryo transfers of blastocysts between June 2013 and September
epithelial cells from mitochondrial damage, suggesting mitochondria in MSC 2017. The study excluded women with known endometriosis or endometrio-
is healthy enough to be good sources for MIT treatment. Therefore, the aim of mas. Each subject was included only once.
this study is to investigate the effect of MIT from autologous MSC in MATERIALS AND METHODS: 204 subjects were not pretreated, 143
improving oocyte quality and clinical outcome in an IVF/ICSI program. received 2-months of luprolide-acetate only, 176 received luprolide acetate
DESIGN: Patients with repeated IVF/ICSI failure due to refractory poor 3.75 mg monthly IM and letrozole 5 mg daily orally for 60 days. Subse-
embryo quality (no good-quality embryos obtained in at least two previous quently, the subjects underwent an estradiol valerate (2mg TID orally) and
IVF cycles) were recruited in this retrospective study. progesterone endometrin 100 mg bid vaginally, supported frozen blastocyst
MATERIALS AND METHODS: 52 patients were recruited in this study. transfer. Data were compared by ANOVA (& Tukey HSD) or Chi-squared
Prior to ovarian stimulation, 20 ml of bone marrow were aspirated from tests. Data are presented as % or mean
SD. Power analysis suggested
each patient’s iliac crest under local anesthesia and BMSCs were isolated, R84 subjects were required in each arm, beta¼0.8, alpha error 0.05 and
cultured and frozen in vitro, and then thawed two days before oocyte retrieval 35% difference. All subjects had a normal uterine cavity, & non-severe
for mitochondria preparation through differential centrifuge. Fluorescent real- male factor infertility and were %40 years female age. Ongoing pregnancies
time PCR was applied to quantify the absolute copy number of mtDNA. All are at least 24 weeks gestation.
mitochondria were suspended in fertilization medium for injection and 2 pl RESULTS: Data is presented as no pre-treatment, GnRH-ag, GnRH-ag-le-
of solution (approximately 4000-5000 copy number of mtDNA) were injected trozole groups respectively. Female age, AFC, basal serum FSH levels dura-
into each mature oocyte together with one sperm during ICSI procedure. tion of infertility, previous pregnancies and full-term deliveries were similar
RESULTS: The average age and number of previous failed IVF cycles of (P>0.05). Number of frozen blastocysts were similar as were Gardner’s
this group of patients were 37.69
5.96 y and 4.75
2.10 respectively. The grade of embryo transferred. All subjects had failed 2 previous blastocyst
mean number of oocytes obtained, mature oocytes, 2PNs, transferrable em- transfers. Clinical Pregnancy rates and third-trimester pregnancies were
bryos and good-quality embryos were 8.04
5.41, 6.06
4.23, 4.54
3.46, highest among the GnRH-ag-letrozole. No difference was noted in the no
2.21
2.19 and 1.48
1.84, respectively. One in three D3 embryos was graded pre-treatment and GnRH-ag groups.
as good-quality after MIT, the rate of good-quality embryo was significantly
higher than that in previous cycles (33.17% vs. 0%, P<0.05). Fresh embryo
transfer was performed in 19 patients, and the pregnancy rate was 31.58% (6/
19). In 18 patients, fresh embryo transfer was cancelled and the mean number GnRH-Ag +
of embryos frozen was 1.61
1.20. Nothing 204 GnRH-ag 143 letrozole 176 P¼
CONCLUSIONS: In summary, transferring mitochondria from autolo-
gous BMSCs into oocytes offer a new potential treatment to rescue compro- Female Age 35.3
3.2 34.8
3.6 35.2
3.0 0.35
mised oocytes and normalizes embryo development without disturbing (Years)
patients’ mtDNA fingerprint. AFC 14.6
2.4 14.0
3.4 14.3
2.9 0.16
References: FSH (IU/L) 8.3
1.4 8.2
1.3 8.0
1.4 0.10
1. Santos TA, EI Shourbagy S, St John JC. Mitochondrial content reflects Prev preg 0.8
0.5 0.7
0.4 0.8
0.6 0.14
oocyte variability and fertilization outcome. Fertil Steril 2006;85:584-91. Prev Deliveries 0.6
0.5 0.6
0.5 0.5
0.5 0.10
2. Tzeng C, Hsieh R, Chang S, et al. Pregnancy derived from mitochondria Days of 10.3
3.3 9.8
3.2 9.9
3.3 0.31
transfer (MIT) into oocyte from patient’s own cumulus granulosa cells stimulation
(cGCs). Fertil Steril 2001;76:S67-8. Gonadotropin 2204
1246 1979
1478 2018
1464 0.26
3. Tzeng CR, Hsieh RH, Au HK, et al. Mitochondria transfer (MIT) into oocyte dose
from autologous cumulus granulose cells (cGCs). Fertil Steril 2004;82:S53. #Frozen Blasts 2.9
1.2 2.7
1.4 2.8
0.6 0.25
4. Oktay K, Baltaci V, Sonmezer M, et al. Oogonial precursor cell-derived autol- Number of 1.2
0.4 1.2
0.3 1.2
0.4 1.0
ogous mitochondria injection to improve outcomes in women with multiple IVF embryos
failures due to low oocyte quality: a clinical translation. Retrod Sci 2015; transferred
22:1612-7. Gardner’s 12% (29) 14% (24) 9% (19) P¼0.38
5. Yi YC, Chen MJ, Ho JY, et al. Mitochondria transfer can enhance the murine grade of
embryo development. J Assist Retrod Genet 2007; 24: 445-9. transferred
6. Kristensen SG, Pors SE, Andersen CY. Improving oocyte quality by transfer embryo AA
of autologous mitochondria from fully grown oocytes. Hum Retrod 2017; AB 28% (68) 31% (53) 28% (59)
32:725-32. BA 42% (103) 33% (57) 44% (93)
7. Acquistapace A, Bru T, Lesault PF, et al. Human mesenchymal stem cells BB 18% (45) 22% (38) 19% (40)
reprogram adult cardiomyocytes toward a progenitor-like state through partial Clin Preg 40% (82/204) 42% (60/143) 63% (111/176) <0.0001
cell fusion and mitochondria transfer. Stem Cells 2011;29:812-24. Ongoing Preg 34% (70/204) 36% (51/143) 56% (99/176) <0.0001
Supported by: No.

e190 ASRM Abstracts Vol. 110, No. 4, Supplement, September 2018