The uterine volume is dramatically decreased after hematopoietic stem cell transplantation during childhood regardless of the conditioning regimen.

OBJECTIVE: 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. SETTING: Thirteen French University Teaching Hospitals. DESIGN: Prospective cohort study. PATIENT(S): Eighty-eight women who underwent HSCT during childhood or adolescence for AL compared to a control group. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Uterine volume, uterine body-to-cervix ratio, and apparent diffusion coefficient. RESULT(S): 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). CONCLUSION(S): 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? CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov/NCT03583294 (enrollment of the first subject, November 11, 2017; enrollment of the last subject, June 25, 2021).

Potential chances for natural fertility influence results of intrauterine inseminations.

OBJECTIVE: Intra-uterine insemination (IUI) is widely used for different indications. The aim of the present study was to evaluate the efficiency of intra-uterine insemination as a function of indication and origin of the inseminated spermatozoa. STUDY DESIGN: The retrospective study involved 827 first attempts of IUI in 827 couples between January 2011 and July 2017 in the Toulouse university hospital. Of these, 642 used fresh sperm from the husband, 40 frozen sperm from the husband and 145 frozen sperm from donors. The measured outcome parameter was live birth rate per attempt. RESULTS: When comparing couples lacking functional gametes (due to male or female causes), to couples who could potentially conceive spontaneously, i.e. subfertile, the latter were found to have a significantly lower live birth rate (18% vs 26%; P < 0.05). Even when adjusted for demographic parameters, which differed significantly between the 2 groups (female age, percentage of women suffering from primary infertility, BMI, number of inseminated motile spermatozoa and stimulation duration), this difference remained statistically significant (OR = 0.639 [0.425-0.961]; P = 0.0316). CONCLUSION: When compared to couples lacking functional gametes, subfertile couples have poor IUI outcomes, suggesting a hidden cause of infertility, despite no apparent differences in ovarian reserve, tubal potency, results of ovarian stimulation and normal conventional sperm parameters. Further studies are required to better characterise and identify this subgroup of women with poor IUI outcomes.

Age-specific anti-Mullerian hormone (AMH) levels poorly affects cumulative live birth rate after intra-uterine insemination.

OBJECTIVE: To evaluate the impact of age-specific anti-Mullerian (AMH) levels on the cumulative live birth rate after 4 intra uterine inseminations (IUI). STUDY DESIGN: The retrospective study study involved 509 couples who underwent their first IUI between January 2011 and July 2017 in the Toulouse University Hospital. All IUI were performed after an ovarian stimulation combining recombinant FSH and GnRH antagonist. The main measure outcome was the cumulative live birth rate (LBR) defined as the number of deliveries with at least one live birth resulting from a maximum of 4 IUI attempts. RESULTS: When compared to normal or high levels, low age-specific AMH (<25th of the AMH in each age group) was associated to a non-significant lower live birth rate (31%, 38% and 42% respectively for low, normal and high age-specific groups; P = 0.170) and non-significant higher miscarriage rate (26%; 19% and 14% respectively for low, normal and high age-specific groups; P = 0.209). However, it must be pointed out that in low age-specific AMH the initial FSH doses used for stimulation were higher than in the other groups. CONCLUSION: This study shows that the age-specific levels of AMH have only a slight effect on IUI outcome when adapting the stimulation protocols to their level.

Association between progesterone to number of mature oocytes index and live birth in GnRH antagonist protocols.

RESEARCH QUESTION: What is the association between blood progesterone level alone, progesterone to mature oocytes index (PMOI) and IVF outcomes? DESIGN: Clinical data from 960 couples undergoing their first fresh embryo transfer after an intracytoplasmic sperm injection attempt carried out between September 2012 and July 2017 were analysed. All patients underwent ovarian stimulation combining recombinant FSH and gonadotrophin releasing hormone antagonist. Progesterone was measured on the day on which ovulation was triggered. The PMOI was divided into four groups based on 25th, 50th and 75th percentiles, and live birth and implantation rates were compared between the groups. RESULTS: A negative association was found between PMOI levels, live birth and implantation rates. When adjusting for age, ovarian stimulation index (OSI) and number of embryos transferred, the PMOI remained negatively correlated to live birth rate (LBR) (OR = 0.147 [0.031 to 0.701]; P = 0.0161), whereas total blood progesterone was no longer evident. Moreover, the LBR (18.5% versus 28.4%; P < 0.01) and implantation rate (12.4% versus 21.0%; P < 0.01) were significantly decreased only when PMOI was 0.167 ng/ml or greater, irrespective of progesterone concentration (< or ≥1.08 ng/ml). The opposite was not true, however. Similar PMOIs were recorded in the same patient from one attempt to the next, and were partially linked to basal FSH, anti-Müllerian hormone, antral follicle count and OSI. CONCLUSIONS: PMOI seems to be more predictive than total progesterone level of IVF outcome and reflects the ability of embryos to develop as it is linked to the implantation rate.

Impact of estradiol and progesterone levels during the late follicular stage on the outcome of GnRH antagonist protocols.

The study aimed to assess the impacts and the targets of progesterone (P4) and estradiol (E2) levels on IVF outcomes in GnRH antagonist protocols. The study was retrospective and concerned patients for their first fresh embryo transfers, after stimulation by a recombinant FSH (rFSH)-GnRH antagonist protocol, between September 2012 and July 2017 in the Toulouse University Hospital. Multivariable analysis, taking into account female age and the ovarian stimulation index, showed that E2 levels had no impact on IVF outcomes, while high P4 levels (>1.10 ng/mL) were associated to low pregnancy rate. The P4 concentrations were significantly negatively correlated to the percentage of top embryos and to the implantation rate. Therefore, the deleterious effect of high levels P4 could to act mainly by impairing embryo quality, which questions the place of the freeze-all strategy in these cases.

Mother's age at menopause but not own age at menarche has an impact on ovarian reserve.

To detect clinical parameters impacting ovarian reserve, data were analyzed from 573 patients who had an anti-Müllerian hormone (AMH) measurement for infertility treatment. No impact was found on the age at menarche but a significant diminished ovarian reserve was observed when a patient's mother was menopausal before age 50. These data suggest that ovarian reserve must be monitored in such patients to offer them fertility preservation when at risk of premature ovarian insufficiency (POI).

Establishment and validation of a score to predict ovarian response to stimulation in IVF.

This study aimed to integrate clinical and biological parameters in a score able to predict ovarian response to stimulation for IVF in gonadotrophin-releasing hormone (GnRH) antagonist protocols. A progressive discriminant analysis to establish a score including the main clinical and biological parameters predicting ovarian response was performed by retrospectively analysing data from the first ovarian stimulation cycle of 494 patients. The score was validated in a prospectively enrolled, independent set of 257 patients undergoing their first ovarian stimulation cycle. All ovarian stimulations were performed using a combination of GnRH antagonist and recombinant FSH. Ovarian response was assessed through ovarian sensitivity index (OSI). Parameters from the patients' database were classified according to correlation with OSI: the progressive discriminant analysis resulted in the following calculation: score = 0.192 - (0.004 × FSH (IU/l)) + (0.012 × LH:FSH ratio) + (0.002 × AMH (ng/ml)) - (0.002 × BMI (kg/m2)) + (0.001 × AFC) - (0.002 × age (years)). This score was significantly correlated with OSI in the retrospective (r = 0.599; P < 0.0001) and prospective (r = 0.584; P < 0.0001) studies. In conclusion, the score including clinical and biological parameters could explain 60% of the variance in ovarian response to stimulation.

Effect of unilateral tubal abnormalities on the results of intrauterine inseminations.

A total of 101 patients with one normal tube were compared with 117 patients with two normal tubes to assess the effect of unilateral tubal abnormalities on the results of intrauterine inseminations. The clinical pregnancy and live birth rates seemed to reduce by one-half in almost all types of abnormality, suggesting that these patients should be preferentially treated with IVF.

Ovarian Mucinous Cystadenoma After Ovarian Graft.

BACKGROUND: Freezing strips of ovarian cortex before chemotherapy followed by transplantation is an experimental method to preserve fertility for reproductive-aged women with cancer. We report a case of a cancer patient who developed a mucinous cystadenoma in a grafted piece of ovarian cortex. CASE: A 32-year-old woman with a Ewing sarcoma had ovarian cryopreservation using cortical strip freezing before receiving chemotherapy. Five years later she had no ovarian function, and the strips were thawed and grafted back onto the ovary. She spontaneously became pregnant 1 year after this procedure and delivered a healthy neonate near term. During the cesarean delivery, a 5×3-cm cyst was removed from the graft. On pathologic evaluation, it was determined to be a mucinous cystadenoma. CONCLUSION: Ovarian pathology can develop in previously frozen ovarian cortex tissue after transplantation back onto the ovary. This suggests that routine gynecologic surveillance remains important for these women.

Follicular growth but absence of oocyte and cumulus maturation during ovarian stimulation in the days following surgical abortion: a case report.

This paper is a case report on the results of an ovarian stimulation performed in the days following an induced abortion. A patient had breast cancer diagnosed during an early pregnancy. She had an induced abortion and had, before chemotherapy an ovarian stimulation, using rFSH and GnRH antagonist, followed by follicular puncture for oocyte for vitrification in the view of fertility preservation. No oocyte could be obtained despite a good hormonal and ultrasonographical follicular growth. This case report suggest that ovarian stimulation must be delayed after abortion to allow the maturation of oocyte-cumulus complexes.

How many embryos should be transferred? A validated score to predict ongoing implantation rate.

OBJECTIVE: To developed a prognostic score to predict ongoing implantation rate according to clinical and biological parameters and to choose the number of embryos to be transferred in patients undergoing IVF/ICSI. STUDY DESIGN: The transfer score was established using multivariate analysis of biological and clinical parameters in 3211 fresh embryo transfers in a retrospective study. Then we validated the score in 694 fresh embryo transfers in a prospective study. We assessed ongoing implantation rates, ongoing pregnancy rates, multiple pregnancy rates and live birth rate. RESULTS: Among the different variables tested, 4 were identified that influenced the implantation rate: female age, the ratio of retrieved oocytes/mean daily dose of injected FSH, attempt rank and the morphology of the embryo cohort. Prospective application of this score resulted in significantly lower number of transferred embryos (1.8 vs 2.0 P<0.001) and lower twins rates (9.7% vs 17.3%, P<0.001) without decreasing live birth rates. CONCLUSION: Although the risks of multiple pregnancies should not be ignored, it appears excessive to impose the limit of 2 embryos for transfer particularly in situations with a poor prognosis. We sought to provide a personalized prognosis by using clinical and embryo data in order to choose the number of embryo(s) for transfer with a moderate multiple pregnancy rate of less than 11%.

Fracture risk in early postmenopausal women assessed using FRAX.

OBJECTIVES: To evaluate FRAX 10-year fracture probabilities depending on the recommended management strategy in early postmenopausal women who were untreated at baseline. METHODS: We conducted a descriptive study in 494 untreated women aged 45-60 years seen for the first time at a menopause clinic. Risk factors, physical findings, and bone mineral density (BMD) values determined by dual-energy X-ray absorptiometry were collected. At the end of the clinic visit, 128 (26%) women were prescribed medications. Then, the 10-year fracture probability was estimated using the FRAX tool. RESULTS: The mean FRAX probability was 3.9%+/-2% for major osteoporotic fractures and 0.8%+/-0.9% for hip fractures. Women who were prescribed medications had significantly (P<0.001) higher probabilities than the other women. The proportion of women prescribed medications increased significantly (P<0.0001) with the FRAX probability, from 7.8% in the lowest quintile (Q1) to 50.5% in Q5. Hormone replacement therapy or raloxifene contributed 92% of the prescriptions in patients with FRAX probabilities in the first four quintiles and bisphosphonates 70% of prescriptions in patients with probabilities in Q5. CONCLUSIONS: Early postmenopausal women had low to moderate fracture risks (FRAX, 3-4%). The indications and type of drugs prescribed correlated with FRAX probabilities. Treatment thresholds should be defined to optimize the management of osteoporosis. In early postmenopausal women, treatment thresholds may vary with the type of treatment.

Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post-partum and review of literature.

Cushing's syndrome due to AdrenoCorticoTropic Hormone (ACTH)-secreting pheochromocytoma has been rarely reported during pregnancy and post-partum. We report the case of a 30-year-old woman who presented 3 months after delivery acute psychiatric signs and rapid progressive features of Cushing's syndrome. Hormonal tests confirmed ACTH-dependant Cushing's syndrome. A computed tomography scan revealed a 25 x 30 mm tumoral mass in the left adrenal gland and octreoscan scintigraphy showed only an uptake of the radiolabelled octreotide by the adrenal tumor. Fractionated 24-h urinary catecholamines and metanephrines were in the normal range, except for slightly increased adrenalin levels. A left laparoscopic adrenalectomy was performed with acute pulmonary oedema following the anesthesia. Histological examination revealed a 3.5 x 2.5 cm adrenal tumor consistent with a pheochromocytoma without signs of malignancy. The tumor cells immunostained for ACTH and diffuse hyperplasia of adrenocortical cells was observed. After surgery and short stay in intensive care unit, clinical and biological signs rapidly improved and both anti-hypertensive treatment and insulin injections were withdrawn. Genetic testing did not reveal germline mutations in RET protooncogene, Von Hippel Lindau and succinate deshydrogenase genes.