The impact of treatment for childhood classical Hodgkin lymphoma according to the EuroNet-PHL-C2 protocol on serum anti-Müllerian Hormone.

STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION: This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION: The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2-5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S): The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Extended Reichardt's Dye-Synthesis and Solvatochromic Properties.

Three new pyridinium-phenolate dyes based on the benchmark solvatochromic dye Betaine 30 were synthesised. The dyes contained phenylene spacers between the donor and acceptor groups. Their UV-Vis absorption spectra were measured, with the dyes showing strong negative solvatochromic behaviour comparable to that of Betaine 30. These results stood in contrast to the behaviour of the π-extended dye Betaine 21, originally reported in 1963. This dye was synthesised and found to be significantly more solvatochromic than previously reported but prone to degrade. All π-extended dyes synthesised were found to be unstable in certain solvents. Although the increased distance between donor and acceptor did not enhance solvatochromism to the extent predicted, it was still determined that the reduced planarity caused by a phenylene spacer is not as detrimental as believed.

Harvesting Triplet Excitons in High Mobility Emissive Organic Semiconductor for Efficiency Enhancement of Light-Emitting Transistors.

Organic light-emitting transistors (OLETs), a kind of highly integrated and minimized optoelectronic device, demonstrate great potential applications in various fields. The construction of high-performance OLETs requires the integration of high charge carrier mobility, strong emission, and high triplet exciton utilization efficiency in the active layer. However, it remains a significant long-term challenge, especially for single component active layer OLETs. Herein, the successful harvesting of triplet excitons in a high mobility emissive molecule, 2,6-diphenylanthracene (DPA), through the triplet-triplet annihilation process is demonstrated. By incorporating a highly emissive guest into the DPA host system, an obvious increase in photoluminescence efficiency along with exciton utilization efficiency results in an obvious enhancement of external quantum efficiency of 7.2 times for OLETs compared to the non-doped devices. Moreover, well-tunable multi-color electroluminescence, especially white emission with Commission Internationale del'Eclairage  of (0.31, 0.35), from OLETs is also achieved by modulating the doping concentration with a controlled energy transfer process. This work opens a new avenue for integrating strong emission and efficient exciton utilization in high-mobility organic semiconductors for high-performance OLETs and advancing their related functional device applications.

Protection of Boronic Acids Using a Tridentate Aminophenol ONO Ligand for Selective Suzuki-Miyaura Coupling.

Boronic acid protecting group chemistry powerfully enhances the versatility of Suzuki-Miyaura cross-coupling. Prominent examples include trifluoroborate salts, N-methyliminodiacetic acid (MIDA) boronates, and 1,8-diaminonaphthalene boronamides. In this work, we present a bis(2-hydroxybenzyl)methylamine (BOMA) ligand that forms tridentate complexes with boronic acids much like the MIDA ligand but the deprotection is facilitated by organic acids. The BOMA boronates showed considerable stability in both aqueous base and acid, and a variety of chemoselective reactions were performed on these boronates, including selective Suzuki-Miyaura coupling, palladium-catalyzed borylation, ester hydrolysis, alkylation, lithiation-borylation, and oxidative hydroxydeboronation.

Unusual Alternating Crystallization-Induced Emission Enhancement Behavior in Nonconjugated ω-Phenylalkyl Tropylium Salts.

The alternating physical properties, especially melting points, of α,ω-disubstituted n-alkanes and their parent n-alkanes had been known since Baeyer's report in 1877. There is, however, no general and comprehensive explanation for such a phenomenon. Herein, we report the synthesis and examination of a series of novel ω-phenyl n-alkyl tropylium tetrafluoroborates, which also display alternation in their physicochemical characters. Despite being organic salts, the compounds with odd numbers of carbons in the alkyl bridge exist as room temperature ionic liquids. In stark contrast to this, the analogues with even numbers of carbons in the linker are crystalline solids. These solid nonconjugated molecules exhibit curious photoluminescent properties, which can be attributed to their ability to form through-space charge-transfer complexes to cause crystallization-induced emission enhancement. Most notably, the compound with the highest photoluminescent quantum yield in this series showed an unusual arrangement of carbocationic dimer in the solid state. A combination of XRD analysis and ab initio calculations revealed interesting insights into these systems.

Application of Triplet-Triplet Annihilation Upconversion in Organic Optoelectronic Devices: Advances and Perspectives.

Organic semiconductor materials have been widely used in various optoelectronic devices due to their rich optical and/or electrical properties, which are highly related to their excited states. Therefore, how to manage and utilize the excited states in organic semiconductors is essential for the realization of high-performance optoelectronic devices. Triplet-triplet annihilation (TTA) upconversion is a unique process of converting two non-emissive triplet excitons to one singlet exciton with higher energy. Efficient optical-to-electrical devices can be realized by harvesting sub-bandgap photons through TTA-based upconversion. In electrical-to-optical devices, triplets generated after the combination of electrons and holes also can be efficiently utilized via TTA, which resulted in a high internal conversion efficiency of 62.5%. Currently, many interesting explorations and significant advances have been demonstrated in these fields. In this review, a comprehensive summary of these intriguing advances on developing efficient TTA upconversion materials and their application in optoelectronic devices is systematically given along with some discussions. Finally, the key challenges and perspectives of TTA upconversion systems for further improvement for optoelectronic devices and other related research directions are provided. This review hopes to provide valuable guidelines for future related research and advancement in organic optoelectronics.

Revealing the influence of steric bulk on the triplet-triplet annihilation upconversion performance of conjugated polymers.

A series of poly(phenylene-vinylene)-based copolymers are synthesized using the Gilch method incorporating monomers with sterically bulky sidechains. The photochemical upconversion performance of these polymers as emitters are investigated using a palladium tetraphenyltetrabenzoporphyrin triplet sensitizer and MEH-PPV as reference. Increased incorporation of sterically bulky monomers leads to a reduction in the upconversion efficiency despite improved photoluminescence quantum yield. A phosphorescence quenching study indicates issues with the energy transfer process between the triplet sensitizer and the copolymers. The best performance with 0.18% upconversion quantum yield is obtained for the copolymer containing 10% monomer with bulky sidechains.

Pyridine End-Capped Polymer to Stabilize Organic Nanoparticle Dispersions for Solar Cell Fabrication through Reversible Pyridinium Salt Formation.

Bulk-heterojunction nanoparticle dispersions in water or alcohol can be employed as eco-friendly inks for the fabrication of organic solar cells by printing or coating. However, one major drawback is the need for stabilizing surfactants, which facilitate nanoparticle formation but later hamper device performance. When surfactant-free dispersions are formulated, a strong limitation is imposed by the dispersion concentration due to the tendency of nanoparticles to aggregate. In this work, pyridine end-capped poly(3-hexylthiophene) (P3HT-Py) is synthesized and included as an additive for the stabilization of P3HT:indene-C60 bis-adduct (ICBA) nanoparticle dispersions. In the presence of acetic acid (AcOH), a surface-active pyridinium acetate end-capped P3HT ion pair, P3HT-PyH+AcO-, is formed which effectively stabilizes the dispersion and hence allows the formation of dispersions with smaller nanoparticle sizes and higher concentrations of up to 30 mg/mL in methanol. The dispersions exhibit an enhanced shelf-lifetime of at least 60 days at room temperature. After the deposition of light-harvesting layers from the nanoparticle dispersions, the ion-pair formation is reversed at elevated temperatures leading to regeneration of P3HT-Py and AcOH. The AcOH evaporates from the active layer, while the performance of the corresponding solar cells is not affected by the residual P3HT-Py in the devices. Enhanced nanoparticle stability is achieved with only 0.017 wt % pyridine in the P3HT/ICBA formulation.

Detection of Urinary Albumin Using a "Turn-on" Fluorescent Probe with Aggregation-Induced Emission Characteristics.

Human serum albumin (HSA) is a broadly used biomarker for the diagnosis of various diseases such as chronic kidney disease. Here, a fluorescent probe TC426 with aggregation-induced emission (AIE) characteristics is reported as a sensitive and specific probe for HSA. This probe is non-emissive in aqueous solution, meanwhile it shows bright fluorescence upon interacting with HSA, which makes it applicable in detecting HSA with a high signal to noise ratio. Besides, the fluorescence of TC426 exhibits a high linear correlation with the concentration of albumin in the range of microalbumin (20-200 mg/L), which has a significant importance for the early diagnosis of glomerulus related diseases. Compared with previously reported HSA probes TPE-4TA and BSPOTPE, TC426 shows comparable anti-interference ability towards creatinine and other major components in urine but is excited by a longer excitation wavelength at the visible light range. Finally, with the established assay, TC426 shows excellent performance in detecting HSA in real human urine, indicating its great potential in practical urinalysis.

Detection of Halomethanes Using Cesium Lead Halide Perovskite Nanocrystals.

The extensive use of halomethanes (CH3X, X = F, Cl, Br, I) as refrigerants, propellants, and pesticides has drawn serious concern due to their adverse biological and atmospheric impact. However, there are currently no portable rapid and accurate monitoring systems for their detection. This work introduces an approach for the selective and sensitive detection of halomethanes using photoluminescence spectral shifts in cesium lead halide perovskite nanocrystals. Focusing on iodomethane (CH3I) as a model system, it is shown that cesium lead bromide (CsPbBr3) nanocrystals can undergo rapid (<5 s) halide exchange, but only after exposure to oleylamine to induce nucleophilic substitution of the CH3I and release the iodide species. The extent of the halide exchange is directly dependent on the CH3I concentration, with the photoluminescence emission of the CsPbBr3 nanocrystals exhibiting a redshift of more than 150 nm upon the addition of 10 ppmv of CH3I. This represents the widest detection range and the highest sensitivity to the detection of halomethanes using a low-cost and portable approach reported to date. Furthermore, inherent selectivity for halomethanes compared to other organohalide analogues is achieved through the dramatic differences in their alkylation reactivity.

Optimising molecular rotors to AIE fluorophores for mitochondria uptake and retention.

Molecular rotors exhibit fluorescence enhancement in a confined environment and thus have been used extensively in biological imaging. However, many molecular rotors suffer from small Stokes shift and self-aggregation caused quenching. In this work, we have synthesised a series of red emissive molecular rotors based on cationic α-cyanostilbene. Profoundly enhanced aggregation-induced emission (AIE) properties and greatly widened Stokes shifts can be achieved by molecular engineering. With specificity to stain mitochondria, we demonstrate a simple approach to achieve cell uptake and retention upon tuning the pyridinium substituent of the dyes.

Bilirubin analogues as model compounds for exciton coupling.

A series of phycobilin analogues have been investigated in terms of coupled excitonic systems. These compounds consist of a monomer, a tetrapyrrole structurally similar to bilirubin (bR), and two conjugated bR analogues. Spectroscopic and computational methods have been used to investigate the degree of interchromophore coupling. We find the synthesised bR analogue shows stronger excitonic coupling than bR, owing to a different molecular geometry. The excitonic coupling in the conjugated molecules can be controlled by modifying the bridge side-group. New computed energy levels for bR using the DFT/MRCI method are also presented, which improve on published values and re-assign the character of excited singlet states.

A luminescent solar concentrator ray tracing simulator with a graphical user interface: features and applications.

A Monte-Carlo ray tracing simulator with a graphical user interface (MCRTS-GUI) has been developed to provide a quantitative description, performance evaluation and photon loss analysis of luminescent solar concentrators (LSCs). The algorithm is applied to several practical LSC device structures including multiple dyes in the same waveguiding layer, and structures where a dye layer is sandwiched between clear substrates. The effect of the host matrix absorption and the influence of the neighboring layers are investigated. Validations demonstrate that the MCRTS-GUI developed provides a reliable and accurate description of LSC performance. Code for the mixed-dye single layer configuration is converted into a ray-tracing package with a user-friendly interface and is made available as open source software.

Triplet fusion upconversion using sterically protected 9,10-diphenylanthracene as the emitter.

Improving the efficiency of triplet fusion upconversion (TF-UC) in the solid-state is still challenging due to the aggregation and phase separation of chromophores. In this work, two 9,10-diphenylanthracene (DPA) derivatives based on the modification of the 9,10-phenyl rings with bulky isopropyl groups (bDPA-1 and bDPA-2) were used as emitters. By using platinum octaethylporphyrin (PtOEP) as the sensitizer, TF-UC performance was comprehensively investigated in 3 media: toluene solution, polyurethane thin film and nano/micro-crystals in a polyvinyl alcohol matrix. Only a small difference in upconversion efficiency between the bulky DPAs and the DPA reference was observed in toluene solution and polyurethane thin film. However, a large improvement of TF-UC quantum yield was achieved in bDPA-2/PtOEP crystals (ΦUC = (0.92 ± 0.05)%) with a low excitation intensity threshold (52 mW cm-2) compared to that of DPA/PtOEP crystals (ΦUC = (0.09 ± 0.03)%). This difference was largely attributed to improved dispersibility of the PtOEP sensitizer in the bDPA-2 emitter crystals. The bulky DPAs also show excellent stability under UV irradiation with exposure to oxygen compared to DPA. These results provide a strategy for developing efficient solid-state TF-UC systems based on nano/micro-particles of emitter-sensitizer mixtures.

A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment.

Environmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general method of using the fluorogenic probe NTPAN-MI is reported to quantify the subcellular polarity change in response to protein unfolding. NTPAN-MI fluorescence is selectively activated upon labeling unfolded proteins with exposed thiols, thereby reporting on the extent of proteostasis. NTPAN-MI also reveals the collapse of the host proteome caused by influenza A virus infection. The emission profile of NTPAN-MI contains information of the local polarity of the unfolded proteome, which can be resolved through spectral phasor analysis. Under stress conditions that disrupt different checkpoints of protein quality control, distinct patterns of dielectric constant distribution in the cytoplasm can be observed. However, in the nucleus, the unfolded proteome was found to experience a more hydrophilic environment across all the stress conditions, indicating the central role of nucleus in the stress response process.

Tetrabenzo[5.7]fulvalene: a forgotten aggregation induced-emission luminogen.

Tetrabenzo[5.7]fulvalene, one of the first recognized stable members of mixed fulvalenes, has attracted widespread interest for its remarkable structure. However, little has been known about its photoactivity, most likely owing to its very weak luminescence in the solution state. Here we show for the first time that this compound exhibits aggregation-induced emission (AIE) properties. Its photoluminescence and X-ray crystal structure reveal an interesting mechanism of the AIE phenomenon.

A Maleimide-functionalized Tetraphenylethene for Measuring and Imaging Unfolded Proteins in Cells.

Collapse of the protein homeostasis (proteostasis) can lead to accumulation and aggregation of unfolded proteins, which has been found to associate with a number of disease conditions including neurodegenerative diseases, diabetes and inflammation. Here we report a maleimide-functionalized tetraphenylethene (TPE)-derivatized fluorescent dye, TPE-NMI, which shows fluorescence turn-on property upon reacting with unfolded proteins in vitro and in live cells under proteostatic stress conditions. The level of unfolded proteins can be measured by flow cytometry and visualized with confocal microscopy.

Tetraphenylethene 9,10-Diphenylanthracene Derivatives - Synthesis and Photophysical Properties.

A series of tetraphenylethene 9,10-diphenylanthracene (TPE-DPA) derivatives have been synthesized, and their photophysical properties studied. Photoluminescence measurements in PMMA, neat films and nanoparticle dispersions reveal that different aggregation states are formed, which leads to different photophysical behavior. The triplet excited state properties were studied using Pt(II) octaethylporphyrin (PtOEP) as triplet sensitizer. Upconverted emission from the DPA moiety is observed in nanoparticle dispersions of each derivative. A higher upconverted emission intensity is observed in aerated (compared to deaerated) solutions of the derivatives following irradiation, which is attributed to oxidation of the TPE moiety. These results provide valuable insight for the design of AIE luminogens for triplet-triplet annihilation upconversion (TTA-UC).

Exciton Dynamics of Photoexcited Pendant Porphyrin Polymers in Solution and in Thin Films.

Several new polymers with rotatable zinc porphyrin pendants have been synthesized and their optical spectroscopic and photophysical properties, including upconversion efficiencies, determined in both fluid solution and thin films. Comparisons made with the ß-substituted zinc tetraphenylporphyrin monomers and ZnTPP itself reveal that the yield of triplets resulting from either Q-band or Soret-band excitation of the polymers is surprisingly small. A detailed kinetic analysis of the fluorescence decays and transient triplet absorptions of the substituted monomers and their corresponding polymers reveals that this phenomenon is due to two parallel internal singlet quenching processes assigned to transient intrachain excimer formation. Consequently, the yields of upconverted S2 fluorescence resulting from Q-band excitation in the degassed polymers are significantly diminished in both fluid solution and thin films. Implications of these results for the design of polymer upconverting systems are discussed.

Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system.

STUDY QUESTION: Can complete oocyte development be achieved from human ovarian tissue containing primordial/unilaminar follicles and grown in vitro in a multi-step culture to meiotic maturation demonstrated by the formation of polar bodies and a Metaphase II spindle? SUMMARY ANSWER: Development of human oocytes from primordial/unilaminar stages to resumption of meiosis (Metaphase II) and emission of a polar body was achieved within a serum free multi-step culture system. WHAT IS KNOWN ALREADY: Complete development of oocytes in vitro has been achieved in mouse, where in vitro grown (IVG) oocytes from primordial follicles have resulted in the production of live offspring. Human oocytes have been grown in vitro from the secondary/multi-laminar stage to obtain fully grown oocytes capable of meiotic maturation. However, there are no reports of a culture system supporting complete growth from the earliest stages of human follicle development through to Metaphase II. STUDY DESIGN, SIZE, DURATION: Ovarian cortical biopsies were obtained with informed consent from women undergoing elective caesarean section (mean age: 30.7 ± 1.7; range: 25-39 years, n = 10). PARTICIPANTS/MATERIALS, SETTING, METHODS: Laboratory setting. Ovarian biopsies were dissected into thin strips, and after removal of growing follicles were cultured in serum free medium for 8 days (Step 1). At the end of this period secondary/multi-laminar follicles were dissected from the strips and intact follicles 100-150 µm in diameter were selected for further culture. Isolated follicles were cultured individually in serum free medium in the presence of 100 ng/ml of human recombinant Activin A (Step 2). Individual follicles were monitored and after 8 days, cumulus oocyte complexes (COCs) were retrieved by gentle pressure on the cultured follicles. Complexes with complete cumulus and adherent mural granulosa cells were selected and cultured in the presence of Activin A and FSH on membranes for a further 4 days (Step 3). At the end of Step 3, complexes containing oocytes >100 µm diameter were selected for IVM in SAGE medium (Step 4) then fixed for analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Pieces of human ovarian cortex cultured in serum free medium for 8 days (Step 1) supported early follicle growth and 87 secondary follicles of diameter 120 ± 6 µm (mean ± SEM) could be dissected for further culture. After a further 8 days, 54 of the 87 follicles had reached the antral stage of development. COCs were retrieved by gentle pressure from the cultured follicles and those with adherent mural granulosa cells (n = 48) were selected and cultured for a further 4 days (Step 3). At the end of Step 3, 32 complexes contained oocytes >100 µm diameter were selected for IVM (Step 4). Nine of these complexes contained polar bodies within 24 h and all polar bodies were abnormally large. Confocal immuno-histochemical analysis showed the presence of a Metaphase II spindle confirming that these IVG oocytes had resumed meiosis but their developmental potential is unknown. LIMITATIONS, REASONS FOR CAUTION: This is a small number of samples but provides proof of concept that complete development of human oocytes can occur in vitro. Further optimization with morphological evaluation and fertilization potential of IVG oocytes is required to determine whether they are normal. WIDER IMPLICATIONS OF THE FINDINGS: The ability to develop human oocytes from the earliest follicular stages in vitro through to maturation and fertilization would benefit fertility preservation practice. STUDY FUNDING/COMPETING INTEREST(S): Funded by MRC Grants (G0901839 and MR/L00299X/1). No competing interests.