We determined the best model available for natural follicle decline in healthy women and used this to calculate the radiosensitivity of the human oocyte.Ovarian failure was diagnosed in six patients with a median age of 13.2 years (range 12.5-16.0) who were treated with total body irradiation (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This estimate is an oversimplification, because decay represents an instantaneous rate of temporal change based upon the remaining population pool, expressed as a differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701 200.Solving the differential equation, we have estimated the number of follicles left after irradiation given as sol(51 - s + r), where r equals age at treatment, s equals age at diagnosis of ovarian failure, and 51 years is the average age of menopause. The surviving fraction of oocytes as a percentage is 100 times this value divided by sol(r). The mean surviving fraction for the six cases is 0.66%. We obtain a function, g(z), which decreases in value from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) = 10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving g(z) = 50 gives an LD(50) of 1.99.Based on new data and a revised mathematical model of natural oocyte decline, we have determined the surviving fraction of oocytes following irradiation and estimate the LD(50) of the human oocyte to be <2 Gy.

Assisted reproduction technologies have substantially advanced since the birth of the first in vitro fertilization baby, and innovations within in vitro fertilization laboratories have been of paramount importance for the overall assisted reproduction technology success rates. However, one of the milestones in the history of in vitro fertilization is irrefutably the introduction of conventional ovarian stimulation. The objective of the present review is to provide an update on conventional ovarian stimulation, by giving an overview of treatment milestones, together with the latest innovations currently being investigated. The realization of an assisted reproduction technology treatment depends on many steps that can be medically manipulated and must be harmoniously combined, starting from the follicular phase and ending with luteal phase support. New technologies in the pharmaceutical sector are fundamental to optimize efficiency and tailor treatment approaches to individual needs. The present review aims to offer physicians a useful summary of the more recent publications and to facilitate the translation of research findings into daily clinical practice.

To review the complex concerns of oncofertility created through increased cancer survivorship and the long-term effects of cancer treatment in young adults.

To determine response to controlled ovarian stimulation in a random start cycle and utilisation of cryopreserved oocytes and embryos in cancer patients.A retrospective cohort study was carried out in an assisted reproductive treatment centre. Participants included 137 cancer patients who underwent controlled ovarian stimulation for fertility preservation between 1 Feb 2003 and 30 June 2016. The primary outcome variable was number of oocytes retrieved. Multivariable logistic regression analysis was performed, and differences compared using Chi squared test and student t-test as appropriate. P <  0.05 was considered statistically significant.Using the antagonist protocol, there was no difference in number of oocytes retrieved between the early follicular phase or at random start stimulation; 11.9 (95% CI 10.3-13.5) and 12.9 (95% CI 9.6-16.2), P =  0.602, respectively. Similarly, the number of embryos frozen was comparable between those starting stimulation in early follicular and random phase, 6.7 (95% CI 5.7-7.7) and 5.1 (95% CI 3.6-6.5), P= 0.1508 respectively. Among patients undergoing fertility preservation, those who returned to attempt a pregnancy had an ongoing pregnancy rate of 24.3%. Overall, 65% of oocytes and embryos were still in storage, however, 16 (11.7%) had elected to have their oocytes or embryos disposed of.For women faced with potential gonadotoxic treatment and requiring urgent fertility preservation, ovarian stimulation with the antagonist protocol can be started at random without compromising ovarian response. Pregnancy rates following utilisation of frozen-thawed oocytes and embryos are promising, however, more research is needed to understand reasons underlying disposition of oocytes and embryos especially when survival following cancer treatment has improved significantly.Copyright © 2018 Elsevier B.V. All rights reserved.

To evaluate COS and oocyte retrieval results in ART treatment cycles initiated at any stage of the menstrual cycle (random start) in cancer patients, who could not postpone the onset of cancer treatment.Prospective observational study of 26 women with cancer, with an indication to start cancer treatment within the next 20 days and wishing to preserve their fertility. Ovarian stimulation started immediately with FSH followed by GnRH antagonist for pituitary suppression and GnRH agonist for oocyte maturation. Treatment started from day 1 to day 14 of the menstrual cycle was considered to be in the follicular phase, and that started from day 15 to day 28 was considered to be in the luteal phase. Oocyte retrieval was performed 34 h after GnRH agonist administration. After identification and maturity classification, metaphase II oocytes were cryopreserved using vitrification.A total of 13 women had breast cancer, 4 ovarian cancer, 3 Central Nervous System cancer, 3 endometrial cancer, 2 cervical cancer and one bowel cancer. Thirteen patients started treatment during follicular phase and 13 during luteal phase. We found similar results for the duration of treatment, total dose of follicle stimulating hormone, number of ampoules of gonadotropin releasing hormone antagonist, mean number of follicles identified at ultrasound on the day of trigger and retrieval, number of aspirated oocytes and Metaphase II oocytes.Random-start controlled ovarian stimulation for emergency fertility preservation for minimizing delay in oncologic treatment for cancer patients does not interfere with the number of metaphase II oocytes, and therefore can be routinely used for stimulation followed by cryopreservation.

Is the total number of oocytes retrieved with dual ovarian stimulation in the same cycle (duostim) higher than with two consecutive antagonist cycles in poor responders?

To assess the clinical contribution of luteal-phase stimulation (LPS) to follicular-phase stimulation (FPS) in a single ovarian cycle (DuoStim) for poor responder patients fulfilling the Bologna criteria.Observational study (years 2015-2017) including women satisfying ≥2 of the following characteristics: maternal age ≥40 years and/or ≤3 oocytes retrieved after previous conventional stimulation and/or reduced ovarian reserve (i.e., antral follicle count <7 follicles or antimüllerian hormone <1.1 ng/mL). The LPS was started regardless of the outcome of the FPS.Private in vitro fertilization center.A total of 100 of 297 patients fulfilling the Bologna criteria chose to undergo DuoStim.The FPS and LPS with the same antagonist protocol and agonist trigger, intracytoplasmic sperm injection with ejaculated sperm, preimplantation genetic testing for aneuploidies, and vitrified-warmed euploid single blastocyst transfer.The contribution of LPS to the cumulative live birth rate (CLBR) per intention-to-treat (ITT).Patients (100) underwent FPS (maternal age, 42.1 ± 1.4 y; previous in vitro fertilization cycles with ≤3 collected oocytes, 0.7 ± 0.9; antral follicle count, 3.8 ± 1.2 follicles; and antimüllerian hormone, 0.56 ± 0.3 ng/mL). Ninety-one patients completed DuoStim. All patients were included in the analysis. More oocytes were obtained after LPS with similar developmental and chromosomal competence as paired FPS-derived ones. The CLBR per ITT increased from 7% after FPS to 15% after DuoStim. Conversely, the CLBR per ITT among the 197 patients that chose a conventional controlled ovarian stimulation strategy was 8%, as only 17 patients who were not pregnant returned for a second stimulation after the first attempt (drop-out rate, 81%).The LPS-derived oocytes increased the CLBR per ITT in a single ovarian cycle in patients fulfilling the Bologna criteria. The DuoStim strategy is promising to manage this thorny population of patients, especially to avoid discontinuation after a first failed attempt.Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

To provide updated fertility preservation (FP) recommendations for people with cancer.A multidisciplinary Expert Panel convened and updated the systematic review.One hundred sixty-six studies comprise the evidence base.People with cancer should be evaluated for and counseled about reproductive risks at diagnosis and during survivorship. Patients interested in or uncertain about FP should be referred to reproductive specialists. FP approaches should be discussed before cancer-directed therapy. Sperm cryopreservation should be offered to males before cancer-directed treatment, with testicular sperm extraction if unable to provide semen samples. Testicular tissue cryopreservation in prepubertal males is experimental and should be offered only in a clinical trial. Males should be advised of potentially higher genetic damage risks in sperm collected soon after cancer-directed therapy initiation and completion. For females, established FP methods should be offered, including embryo, oocyte, and ovarian tissue cryopreservation (OTC), ovarian transposition, and conservative gynecologic surgery. In vitro maturation of oocytes may be offered as an emerging method. Post-treatment FP may be offered to people who did not undergo pretreatment FP or cryopreserve enough oocytes or embryos. Gonadotropin-releasing hormone agonist (GnRHa) should not be used in place of established FP methods but may be offered as an adjunct to females with breast cancer. For patients with oncologic emergencies requiring urgent oncologic therapy, GnRHa may be offered for menstrual suppression. Established FP methods in children who have begun puberty should be offered with patient assent and parent/guardian consent. The only established method for prepubertal females is OTC. Oncology teams should ensure prompt access to a multidisciplinary FP team. Clinicians should advocate for comprehensive FP services coverage and help patients access benefits.Additional information is available at www.asco.org/survivorship-guidelines.

This study evaluated the current status of reproductive disorders and provision of information on oncofertility to female adolescent and young adult (AYA) cancer patients in Japan.

Ovarian tissue cryopreservation (OTC) is the only fertility preservation option for premenarcheal girls before gonadotoxic treatment, but is still considered to be experimental in pediatric patients. This study investigated storage behaviors across different age groups to refine counseling approaches for pediatric patients.

We report a rare case of ovarian hyperstimulation syndrome (OHSS) in a 28-year-old woman with breast cancer and with a history of polycystic ovary syndrome (PCOS) despite treatment with letrozole and gonadotropin-releasing hormone agonist (GnRH-a) triggering in a GnRH antagonist (GnRH-ant) protocol without the administration of any human chorionic gonadotropin (hCG) for luteal-phase support. The patient, who underwent controlled ovarian syndrome (COS)-oocyte cryopreservation before chemotherapy, required hospitalization. Complete recovery was achieved after treatment with volume expanders, human albumin, and cabergoline. Based on our case and literature review, it is possible to establish that estradiol (E2) modulation with letrozole and GnRH-a triggering does not eliminate the risk of OHSS. Furthermore, it is advisable to postpone GnRH-a depot to minimize the risk of OHSS after the suspension of letrozole, following menstruation or at least 7–8 days after triggering. It would be desirable to identify high-risk patients, also on a genetic basis, in order to avoid delays in oncologic treatments that could strongly impact life expectancy.

The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.© 2024. The Author(s).

In-vitro maturation (IVM) is the process of cultivating early-stage follicles from the primordial to the antral stage and facilitating the maturation of oocytes outside the body within a supportive environment. This intricate procedure requires the careful coordination of various factors to replicate the natural ovarian conditions. Advanced techniques for IVM are designed to mimic the natural ovarian environment and enhance the development of follicles. Three-dimensional (3D) culture systems provide a more biologically relevant setting for follicle growth compared to traditional two-dimensional (2D) cultures. Traditional culture systems, often fail to support the complex process of follicle development effectively. However, modern engineered reproductive tissues and culture systems are making it possible to create increasingly physiological in-vitro models of folliculogenesis. These innovative methods are enabling researchers and clinicians to better replicate the dynamic and supportive environment of the ovary, thereby improving the outcomes of IVM offering new hope for fertility preservation and treatment. This paper focuses on the routine 3D culture, and innovative 3D culture of ovary and follicles, including a tissue engineering scaffolds, microfluidic (dynamic) culture system, organ-on-chip models, EVATAR system, from a clinical perspective to determine the most effective approach for achieving in-vitro maturation of follicles. These techniques provide critical support for ovarian function in various ovarian-associated disorders, including primary ovarian insufficiency (POI), premature ovarian failure (POF), ovarian cancer, and age-related infertility.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.