To study the impact of hematopoietic stem cell transplantation (HSCT) on the uterine volume of childhood acute leukemia (AL) survivor depending on age at HSCT and the type of myeloablative ...conditioning regimen.
Thirteen French University Teaching Hospitals.
Prospective cohort study.
Eighty-eight women who underwent HSCT during childhood or adolescence for AL compared to a control group.
A multicentric prospective national study compared the uterine volume in a cohort of childhood AL survivor adult women treated with HSCT, matched 1:1 to control women. Pelvic magnetic resonance imaging scans included diffusion-weighted imaging sequences. Scans were centralized for a double-blinded reading by 2 radiologists.
Uterine volume, uterine body-to-cervix ratio, and apparent diffusion coefficient.
The mean age at HSCT was 9.1 ± 0.3 years with a mean follow-up duration of 16.4 ± 0.5 years. The cohort of 88 HSCT survivor women was composed of 2 subgroups depending on the myeloablative conditioning regimen received: an alkylating agent–based regimen group (n = 34) and a total body irradiation (TBI)–based regimen group (n = 54). Among the 88 women, 77 were considered as having a “correct hormonal balance” with estrogens supplied by hormone replacement therapy (HRT) for premature ovarian insufficiency (POI) or because of a residual ovarian function. In the control group (n = 88), the mean uterine volume was 79.7 ± 3.3 mL. The uterine volume significantly decreased in all HSCT survivor women. After the alkylating agent–based regimen, the uterine volume was 45.3 ± 5.6 mL, corresponding to a significant volume reduction of 43.1% (28.8–57.4%) compared with that of the control group. After TBI, the uterine volume was 19.6 ± 1.9 mL, corresponding to a significant volume reduction of 75.3% (70.5%–80.2%) compared with that of the control group. After the alkylating agent–based regimen, the uterine volume dramatically decreased in women with POI without HRT compared with that in those with a correct hormonal balance (15.2 ± 2.6 vs. 49.3 ± 6 mL). In contrast, after TBI, the uterine volume was similar in all women, with no positive effect of hormonal impregnation on the uterine volume (16.3 ± 2.6 vs. 20.1 ± 2.2 mL, respectively).
The uterine volume was diminished after HSCT, regardless of the conditioning regimen. The physiopathology needs to be further investigated: specific impact of a high dose of an alkylating agent; impact of hormone deprivation around puberty; poor compliance to HRT; or different myometrial impact of HRT compared with endogenous ovarian estrogens?
ClinicalTrials.gov/NCT 03583294 (enrollment of the first subject, November 11, 2017; enrollment of the last subject, June 25, 2021).
El volumen uterino se ve drásticamente reducido después de un transplante de células madre hematopoyéticas durante la infancia independientemente del régimen de acondicionamiento previo.
Estudiar el impacto del transplante de células madre hematopoyéticas (HSCT) sobre el volumen uterino en las supervivientes de leucemia aguda infantil (AL) según la edad en que se realizó el HSCT y el tipo de régimen de acondicionamiento mieloablativo.
Trece hospitales universitarios franceses.
Estudio prospectivo de cohortes.
Ochenta y ocho mujeres sometidas a HSCT durante su infancia o adolescencia por AL comparadas con un grupo control.
Se comparó el volumen uterino en una cohorte de mujeres adultas supervivientes de AL infantil tratada mediante HSCT en un estudio nacional prospectivo multicéntrico, emparejadas 1:1 con mujeres control. Las imágenes de las resonancias magnéticas pélvicas incluyeron secuencias de imágenes ponderadas por difusión. Las pruebas se centralizaron para una lectura doble-ciego realizada por 2 radiólogos.
Volumen uterino, relación cuerpo-cérvix uterino y coeficiente de difusión aparente.
La edad media en la realización del HSCT fue de 9.1+/- 0.3 años, con una media de duración del seguimiento de 16.4 +/- 0.5 años. La cohorte de 88 mujeres supervivientes de HSCT estaba compuesta por 2 subgrupos dependiendo del régimen de acondicionamiento mieloablativo recibido: un grupo con régimen basado en agentes alquilantes (n=34) y otro con régimen basado en irradiación corporal total (TBI) (n=54). Entre las 88 mujeres, se consideró que 77 tenían un “balance hormonal correcto” con aporte de estrógenos mediante tratamiento hormonal sustitutivo (HRT) por insuficiencia ovárica prematura (POI) o por una función ovárica residual. En el grupo control (n=88), el volumen uterino medio fue de 79.7 +/- 3.3 mL. El volumen uterino estaba significativamente reducido en todas las mujeres supervivientes de HSCT. Tras el régimen basado en agentes alquilantes, el volumen uterino era de 45.3 +/- 5.6 mL, correspondiente a una reducción significativa del volumen del 43.1% (28.8-57.4%) comparada con las del grupo control. Después de TBI, el volumen uterino fue de 19.6 +/- 1.9 mL, correspondiente a una reducción significativa del volumen del 75.3% (70.5%-80.2%) comparadas con las del grupo control. Tras el régimen basado en agentes alquilantes, el volumen uterino disminuyó drásticamente en mujeres con POI sin HRT comparadas con aquellas que tenían un balance hormonal correcto (15.2 +/- 2.6 vs. 49.3 +/- 6 mL). Por el contrario, después de TBI, el volumen uterino fue similar en todas las mujeres, sin efecto positivo de la impregnación hormonal sobre el volumen uterino (16.3 +/- 2.6 vs 20.1 +/-2.2 mL respectivamente).
Después de HSCT se produjo una reducción del volumen uterino independientemente del régimen de acondicionamiento. Son necesarios más estudios para conocer la fisiopatología: impacto específico de altas dosis de agentes alquilantes, impacto de la deprivación hormonal en la pubertad, bajo cumplimiento del HRT o diferente impacto miometrial de la HRT comparada con los estrógenos ováricos endógenos?
Útero, transplante de células madre hematopoyéticas, MRI, quimioterapia, irradiación corporal total.
Context: Prokineticin 1 (PROK1) quantification in global follicular fluid (FF) has been recently reported as a predictive biomarker of in vitro fertilization (IVF) outcome. It is now necessary to ...evaluate its clinical usefulness in individual follicles. Objectives: To evaluate the clinical value of PROK1 secretion in individual FF to predict oocyte competence. To determine the impact of follicular size, oocyte maturity, and gonadotropin treatments on PROK1 secretion. Design and setting: Prospective cohort study from May 2015 to May 2017 at the University Hospital of Grenoble. Patients: A total of 69 infertile couples underwent IVF. Intervention(s): Collection of 298 individual FF from 44 women undergoing IVF; 52 individual cumulus cell (CC) samples and 15 CC primary cultures from 25 women undergoing IVF-intracytoplasmic sperm injection (ICSI). Main Outcome Measure(s): Oocyte competence was defined as the ability to sustain embryo development to the blastocyst stage. Follicular size was measured by 2D-sonography. PROK1 concentration was quantified by ELISA assay. Results: PROK1 concentration was correlated to follicular size (r = 0.85, P = 2.2 × 10–16). Normalized PROK1 concentration in FF was predictive of subsequent oocyte competence (AUROC curve = 0.76 95% CI, 0.69–0.83; P = 1.7 × 10–9), irrespectively of day-2 embryo morphokinetic parameters. The expression and secretion of PROK1 were increased in FF and CC of mature oocytes (P < 0.01). Follicle Stimulating Hormone and hCG up-regulated PROK1 secretion in CC primary cultures (P < 0.01; P < 0.05), probably through the cAMP pathway (P < 0.01). Conclusions: PROK1 quantification in individual FF could constitute a new predictive biomarker of oocyte competence in addition with embryo morphokinetic parameters. Trial registration number: none.
Context:
Prokineticin 1 (PROK1), also called endocrine gland–derived vascular endothelial growth factor, is a well-established regulator of endometrial receptivity and placental development. However, ...its clinical usefulness as a noninvasive predictive biomarker of embryo implantation is yet to be validated.
Objective:
The main objective of this article was to determine the relationship between PROK1 levels in the follicular fluid (FF) and fertilization culture media (FCM) and the reproductive outcome in patients who received a first conventional in vitro fertilization–embryo transfer. The secondary objective was to characterize the expression of PROK1 and its receptors (PROKRs) in the human follicular microenvironment.
Design and Setting:
We conducted a prospective study between January 2013 and June 2015 at the University Hospital of Grenoble.
Patients:
A total of 135 infertile in vitro fertilization patients and 10 women undergoing ovarian tissue cryopreservation were included.
Interventions:
The PROK1 concentration was measured by ELISA in FF and FCM collected on the day of oocyte retrieval and the day of the oocyte denudation step, respectively. Follicular expression of the PROK1/PROKR system was determined by immunohistochemistry, RT-quantitative PCR, and ELISA.
Main Outcome Measure:
Assessment of the clinical pregnancy rates was the main outcome.
Results:
FF and FCM PROK1 levels were significantly higher in the embryo implantation group (P < .001) and were predictive of subsequent embryo implantation (area under the receiver operating characteristic curve, 0.91 95% confidence interval, 0.81–1.00, P = .001; and 0.88 0.72–1.00, P = .001, respectively). FF and FCM PROK1 levels remain similar irrespective of the embryo morphokinetic parameters (P = .71 and P = .83, respectively). The PROK1/PROKR system is expressed during human folliculogenesis.
Conclusions:
PROK1 levels in FF and FCM could constitute new predictive noninvasive markers of successful embryo implantation in conventional in vitro fertilization-embryo transfer.
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