Mitochondrial DNA depletion in oocytes of HIV-infected antiretroviral-treated infertile women.
BACKGROUND
HIV-infected women under highly active antiretroviral therapy (HAART) undergoing in vitro fertilization (IVF) have a lower pregnancy rate than noninfected controls, which depends on oocyte-related factors. We hypothesized that mitochondrial toxicity caused by antiretrovirals could be the underlying mechanism of such disturbance.


METHODS
We have studied 16 and 19 frozen-thawed oocytes obtained after oocyte retrieval IVF cycles from 8 and 14 infertile HIV-infected and uninfected women, respectively, matched by age. At inclusion, HIV-positive women had been infected for >13 years and had received HAART for >9 years, including at least one nucleoside reverse transcriptase inhibitor. All of them had undetectable HIV viral load and a good immunological status. Mitochondrial DNA (mtDNA) content was determined by quantitative real-time PCR in each individual oocyte.


RESULTS
HIV-infected infertile women on HAART showed significant oocyte mtDNA depletion when compared with uninfected controls (32% mtDNA decrease, P<0.05). This oocyte mtDNA depletion was even greater on those HIV-infected women who failed to become pregnant when compared with controls (39% mtDNA decrease, P=0.03). No significant correlation was found between mtDNA oocyte content and cumulative doses of antiretrovirals or the immunological status of HIV patients.


CONCLUSIONS
Oocytes from infertile HIV-infected HAART-treated women show decreased mtDNA content, and this could explain their poor reproductive outcome.
Mitochondrial Research Laboratory, Internal Medicine Department, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
Sònia
S
López
Oriol
O
Coll
Mercè
M
Durban
Sandra
S
Hernàndez
Ricard
R
Vidal
Anna
A
Suy
Constanza
C
Morén
Jordi
J
Casademont
Francesc
F
Cardellach
Daniel
D
Mataró
Oscar
O
Miró
Glòria
G
Garrabou
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005307:Fertilization in Vitro; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007246:Infertility / Q000150:complications / Q000628:therapy; D009865:Oocytes / Q000737:chemistry / Q000187:drug effects*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial