M. Grynberg

What threshold values of antral follicle count and serum AMH levels should be considered for oocyte cryopreservation after in vitro maturation

STUDY QUESTIONnWhat threshold values of ultrasonographic antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) levels should be considered for ensuring the cryopreservation of sufficient number of in vitro matured (IVM) oocytes, in cancer patients seeking fertility preservation (FP)?nnnSUMMARY ANSWERnAFC and serum AMH values >20 follicles and 3.7 ng/ml, respectively, are required for obtaining at least 10 IVM oocytes for cryopreservation.nnnWHAT IS KNOWN ALREADYnIVM of cumulus oocyte complexes (COCs) followed by oocyte cryopreservation has emerged recently as an option for urgent FP. Recent data have reported that, in healthy patients, 8-20 cryopreserved oocytes after ovarian stimulation would maximize the chance of obtaining a live birth. Although both AFC and AMH have been reported as predictive factors of IVM success in infertile patients with polycystic ovary syndrome (PCOS), there is a dramatic lack of data regarding the values of these parameters in oncological patients as candidates for FP.nnnSTUDY DESIGN, SIZE, DURATIONnFrom January 2009 to April 2015, we prospectively studied 340 cancer patients, aged 18-41 years, as candidates for oocyte cryopreservation following IVM.nnnPARTICIPANTS/MATERIALS, SETTING, METHODSnAll patients had AFC and AMH measurements, 48-72 h before oocyte retrieval, regardless of the phase of the cycle. COCs were recovered under ultrasound guidance 36 h after hCG priming. Logistic regression allowed the determination of threshold values of AFC and AMH, for obtaining at least 8, 10 or 15 matures oocytes frozen after the IVM procedure. Similar analyses were performed for a final number of mature oocytes ≤2.nnnMAIN RESULTS AND THE ROLE OF CHANCEnAmong the 340 cancer patients included, 300 were diagnosed with breast cancers, 14 had hematological malignancies and 26 underwent the procedure for others indications. Overall, the mean age of the population was 31.8 ± 4.5 years. Mean AFC and serum AMH levels were 21.7 ± 13.3 follicles and 4.4 ± 3.8 ng/ml, respectively. IVM was performed in equal proportions during the follicular or luteal phase of the cycle (49 and 51%, respectively). Statistical analysis showed that AFC and AMH values above 28 follicles and 3.9 ng/ml, 20 follicles and 3.7 ng/ml and 19 follicles and 3.5 ng/ml are required, respectively, for obtaining at least 15, 10 or 8 frozen IVM oocytes with a sensitivity ranging from 0.82 to 0.90. On the contrary, ≤2 IVM oocytes were cryopreserved when AFC and AMH were <19 follicles and 3.0 ng/ml, respectively.nnnLIMITATIONS, REASONS FOR CAUTIONnAlthough the potential of cryopreserved IVM oocytes from cancer patients remains unknown, data obtained from infertile PCOS women have shown a dramatically reduced competence of these oocytes when compared with that of oocytes recovered after ovarian stimulation. As a consequence, the optimal number of IVM oocytes frozen in candidates for FP is currently unpredictable.nnnWIDER IMPLICATIONS OF THE FINDINGSnCryopreservation of oocytes after IVM should be considered in the FP strategy when ovarian stimulation is unfeasible, in particular when markers of the follicular ovarian status are at a relatively high range. Further investigation is needed to objectively assess the real potential of these IVM oocytes after cryopreservation. Therefore, even when a good COCs yield is expected, we should systematically encourage IVM in combination with ovarian tissue cryopreservation.nnnSTUDY FUNDING/COMPETING INTERESTSnNo external funding was obtained for the present study. The authors have no conflict of interest to declare.nnnTRIAL REGISTRATION NUMBERnNot applicable.

Introduction: Male fertility preservation: innovations and questions

It is now well established that many benign or malignant diseases may by themselves or as result of treatment, impair male fertility. Therefore, preserving the potential of becoming a genetic father represents a major issue. Besides sperm cryopreservation, which is the most reliable method for male fertility preservation, other strategies have more recently emerged, especially in prepubertal boys. Prepubertal germ cell storage from testicular sperm extraction and derivation of male gametes from stem cells may represent a future hope, although raising many ethical issues.

Live birth after frozen-thawed oocytes matured in vitro in a PCOS patient: a model for improving implantation rates in IVM cycles and objectively assessing the real potential of development of frozen oocytes matured in vitro

Abstract Over the past 20 years, in vitro maturation (IVM) of oocytes has emerged in the strategy of infertility treatment, with the main indication being in patients suffering from polycystic ovarian syndrome (PCOS). More recently, IVM has been proposed as an option for fertility preservation in women having to undergo gonadotoxic treatments. However, despite the increasing application of IVM, the potential of development of in vitro matured oocytes after thawing remains ill-established and few pregnancies have been reported so far. We report herein a case of live birth after frozen-thawed oocytes matured in vitro and embryo transfer during an artificial cycle in a 29-year-old patient with primary infertility due to PCOS. The present case demonstrates that the transfer of frozen-thawed IVM oocytes during an artificial cycle in PCOS patients is feasible and leads to pregnancy and live birth. This strategy may also be an interesting option to objectively assess the developmental potential of these oocytes after freezing and thawing, which is a major concern for physicians who include the IVM approach in their fertility preservation program.

Préservation de la fertilité dans le cancer du sein : où en est-on en 2014 ?

Fertility preservation has become the second major objective in association with the remission, in young patients suffering from breast cancer. Patients should be referred for oncofertility counseling, as soon as possible after the diagnosis. A multidisciplinary approach, involving oncologists, reproductive endocrinologists and embryologists will allow an optimal strategy according to patients age, the ovarian reserve and the cancer treatments. The field of fertility preservation is improving and offers more and more flexible techniques. Oocyte vitrification is no more considered experimental. Ovarian stimulation combining exogenous FSH and aromatase inhibitors may be the optimal strategy of fertility preservation, while maintaining physiologic serum estradiol levels. In vitro maturation of oocyte may offer an interesting option, possibly in combination with ovarian tissue cryopreservation, in case of neo-adjuvant chemotherapy. All these techniques should not be considered only as a frozen hope but should be part of the treatment of young patients.

Medical techniques of fertility preservation in the male and female

Therapeutic advances in many medical fields have led to the need to consider patient quality of life after curative medico-surgical treatments for malignancy. Thus, it has become a major issue for young patients to preserve the ability to become genetic parents, with their own gametes. While the preservation of male fertility has been an established technique for more than 30 years, it is only in the last decade that progress in cryopreservation techniques has allowed surgeons to offer successful oocyte and ovarian tissue cryobanking. However, in addition to the still experimental nature of some fertility preservation techniques, this practice also raises many ethical and moral questions.

Impact des gonadotrophines chez des patientes traitées pour cancer

The role of gonadotropins in the genesis of malignant diseases, in particular gynecologic cancers, is still controversial. The production of ovarian steroids, as a consequence of FSH and LH actions, may constitute a bias to draw reliable conclusions. Over the past decades, the use of exogenous gonadotropins has markedly increased in cancer patients, candidates for fertility preservation, and in survivors facing infertility as a consequence of gonadotoxic treatments. In gynecologic cancers, high serum estradiol levels may be problematic and can therefore be overcome by specific protocols of ovarian stimulation. However, exogenous gonadotropin administration in cancer patients should systematically be included in a multidisciplinary approach. The present article discusses the possible role of gonadotropins as tumorigenic factors and the use of exogenous gonadotropins in females suffering from cancer.

The Resistant Ovary Syndrome

The “resistant ovary syndrome” or “Savage syndrome” is a rare cause of hypergonadotropic hypogonadism, in which the ovaries are resistant to follicle-stimulating hormone (FSH), leading to a primary or secondary amenorrhea with high gonadotropin levels (FSH and Luteinizing hormone (LH)) despite a normal ovarian follicle pool.

GnRH agonist (GnRHa) priming increases the number of in vitro matured (IVM) oocytes available for cryopreservation in cancer patients seeking urgent fertility preservation (FP)

E2 and follicular size and may complicate clinical decision making. This study seeks to determine whether continuous AI use throughout stimulation impacts oocyte maturity and function. DESIGN: Retrospective. MATERIALS AND METHODS: FP patients with breast cancer treated with an AI (letrozole) were compared to FP patients with other malignancies not using AIs. The AI group had oocyte maturation induced when leading follicles reached 20mm as suggested by Oktay et al, compared with the standard of 18mm. Endocrine levels, oocyte maturity (MII/retrieved oocytes), MII yield (MII/follicles R14mm) and fertilization rates were compared. RESULTS: 24 AI patients were compared with 22 controls. The age, AMH, and antral follicle counts were equivalent. In contrast to prior reports, total gonadotropin usage was similar. The AI group had lower peak E2 levels (536 vs 1972 pg/mL; P 400 pg/mL). The AI group had higher peak P levels (1.1 vs 0.7 ng/mL; P<0.01) and a trend toward a higher risk of premature P rise R1.5 ng/mL (29% vs 5%; P1⁄40.06). Despite larger follicles, the AI group had a lower maturity rate (68% vs 80%; P<0.001). The MII yield was lower in the AI group (P1⁄40.04). Among those who underwent ICSI (15 AI, 14 noAI), the fertilization rate was lower in the AI group (76% vs 84%; P1⁄40.03). CONCLUSION: Despite efforts to prevent supraphysiologicE2 inbreast cancer FP cycles, most AI stimulations result in elevated E2 levels. Although the impact of elevated P on oocyte quality in FP cycles is not established, it may reflect an altered intrafollicular endocrine milieu and post-maturity. Caution shouldbe exercisedwhenchangingdecisionmaking inFPpatients receivingAIs.