Intrafollicular Transfer of Immature Oocytes (IFIOT) has emerged as an alternative to the currently used systems for bovine embryo production. This technique associates the rapid multiplication of bovine females under a completely in vivo culture condition, eliminating the need for superstimulatory hormones in the in vivo system (IVD) and the costly laboratory setup required for in vitro embryo production (IVP). Despite being a promising technique, the results obtained to date have been unsatisfactory for commercial use. Only approximately 10 % -12 % of viable embryos are recovered from the total number of injected oocytes, which limits their use in genetic improvement programs. IFIOT problems can occur in any of the steps involved; therefore, each step must be carefully examined to identify those that have the most negative impact on the final embryo recovery. This review summarizes the different studies conducted using the IFIOT to provide a comprehensive analysis of the main factors that can influence the effectiveness of this technique.

There is still no consensus regarding the role of lipid modulators during in vitro embryo production. Thus, we investigated how lipid reducers during the in vitro maturation of oocytes (IVM) or in vitro culture (IVC) of embryos impact their cryotolerance. A literature search was performed using three databases, recovering 43 articles for the systematic review, comprising 75 experiments (13 performed in IVM, 62 in IVC) and testing 13 substances. In 39 % of the experiments, an increase in oocyte and/or embryo survival after cryopreservation was reported, in contrast to 48 % exhibiting no effect, 5 % causing negative effects, and 8 % influencing in a dose-dependent manner. Of the 75 experiments extracted during IVM and IVC, 41 quantified the lipid content. Of those that reduced lipid content (n = 26), 50 % increased cryotolerance, 34 % had no effect, 8 % harmed oocyte/embryo survival, and 8 % had different results depending on the concentration used. Moreover, 28 out of the 43 studies were analyzed under a meta-analytical approach at the IVC stage in cattle. There was an improvement in the cryotolerance of bovine embryos when the lipid content was reduced. Forskolin, l-carnitine, and phenazine ethosulfate positively affected cryotolerance, while conjugated linoleic acid had no effect and impaired embryonic development. Moreover, fetal bovine serum has a positive impact on cryotolerance. SOF and CR1aa IVC media improved cryotolerance, while mSOF showed no effect. In conclusion, lipid modulators did not unanimously improve cryotolerance, especially when used in IVM, but presented positive effects on cryotolerance during IVC when reaching lipid reduction.

The embryo produced by in vitro oocyte maturation, fertilization, and embryonic development is an important resource for genetic improvement and has the potential to improve female fertility and to be programmed to produce offspring with superior ability for health and production. The cultured embryo is also an important component of several realized and potential technologies such as gene editing, somatic cell nuclear cloning, stem cell technologies and gamete generation in vitro. Full realization of the opportunities afforded by the in vitro-produced embryo will require overcoming some technical obstacles to cost-effective implementation of an embryo transfer program. Among the research goals for improving the penetration of embryo transfer in the cattle industry are development of methods to increase the supply of oocytes from genetically elite females, enhance the proportion of oocytes that become transferrable embryos, improve the fraction of embryos that establish pregnancy after transfer, reduce pregnancy wastage after pregnancy diagnosis, and identify culture conditions to optimize postnatal phenotype.

McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer.

Oocyte in vitro maturation (IVM) has been proposed as an alternative to conventional ovarian stimulation (COS) in subfertile women with polycystic ovary syndrome. To evaluate the effectiveness and safety of IVM compared with COS in women with predicted hyperresponse to gonadotropins, we searched the published literature for relevant studies comparing any IVM protocol with any COS protocol followed by in vitro fertilization or intracytoplasmic sperm injection. A systematic review was undertaken on 3 eligible prospective studies. Live birth rate was not significantly lower after IVM vs. COS (odds ratio [95% confidence interval] of 0.56 [0.32-1.01] overall, 0.83 [0.63-1.10] for human chorionic gonadotropin (hCG)-triggered IVM [hCG-IVM] and 0.45 [0.18-1.13] for non-hCG-triggered IVM [non-hCG-IVM]), irrespective of the stage of transferred embryos. Data from nonrandomized studies generally showed either significantly low or statistically comparable rates of live birth with IVM vs. COS. Most studies have not identified any significant difference between IVM and COS with respect to the rates of obstetric or perinatal complications, apart from a potentially higher rate of hypertensive disorders during pregnancy. The development of offspring from IVM and COS with in vitro fertilization or intracytoplasmic sperm injection appears to be similar. Additional research is needed to identify which patient populations will benefit most from IVM, to define the appropriate clinical protocol, and to develop the optimal culture system.

Our review aimed to consolidate the latest update on the application of in vitro maturation among immature oocyte harvest in combination with ovarian tissue cryopreservation known as ovarian tissue oocyte-in vitro maturation.
A thorough search for relevant studies was conducted via PubMed, Google Scholar, EMBASE, and clinical.gov databases up to December 2020. The primary outcome was the oocyte maturation rate, which measured the number of immature oocytes (geminal vesicle stage) that progressed to mature oocytes (meiosis II stage) following in vitro maturation. The secondary outcomes were the fertilization rate following intracytoplasmic sperm injection/in vitro fertilization of these oocytes for the embryo cryopreservation cohort. Our review included pre-pubertal girls and women with cancer who underwent ovarian tissue oocyte-in vitro maturation as fertility preservation.
The primary search identified 207 studies. Twelve manuscripts were selected for inclusion in our review following duplication assessment, title and abstract screening, and full-text evaluation tailored to our inclusion criteria. All the population belonged to a cancer group and underwent concurrent ovarian tissue oocyte-in vitro maturation. A total of 5724 immature oocytes were obtained following ovarian tissue cryopreservation. Approximately 33.84% of the immature oocytes successfully matured via in vitro maturation, which were cryopreserved as oocytes or fertilized as embryos and subsequently stored for future use.
Our review proposed the potential application of ovarian tissue oocyte-in vitro maturation in increasing the number of mature oocytes. The acceptable improvement in oocyte maturation rate following in vitro maturation indicates that improving oocyte outcomes is an excellent cost-effective strategy for fertility preservation among women with cancer.

Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding of its regulation can be a powerful tool for better in vitro blastocyst production. This systematic review aims to map the evidence of PI3K/AKT/PTEN pathway modulation during in vitro maturation (IVM), to assess its effects on meiosis resumption and nuclear maturation progression of mammalian oocytes, and their impacts on embryo development and quality. A total of 1058 articles were screened in three databases, and 22 articles were included. Fifty-two IVM assessments were identified, among which 11 evaluated blastocyst yield. Three PI3K inhibitors (3-methyladenine, Wortmannin, and LY294002) and one AKT inhibitor (SH6) were investigated. The impact of this pathway modulation on meiosis resumption in swines and murines was not well established, depending on the inhibitor used, concentration, and media supplementation, while in bovines, resumption seems to be independent of PI3K/AKT/PTEN pathway. However, progression to metaphase II (MII) is highly controlled by this pathway on both bovines and swines. Studies that focused on the inhibition reversibility showed that the removal of the modulator produced MII rates similar to the control group. Experiments that aimed to temporarily block meiosis resumption or reduce PI3K activity resulted in blastocyst production equal to or even higher than control groups. Altogether, these data indicate the paramount potential of this pathway as a possible strategy to improve overall in vitro embryo production efficiency, by synchronizing both nuclear and cytoplasmic maturation.

Simulated Physiological Oocyte Maturation (SPOM) mimics in vitro the physiological events of oocyte maturation. The system uses cAMP modulators in two steps (pre IVM and IVM) and has presented promising results that are arousing the curiosity of IVF programs in different animal species, generating several papers, adaptations, and controversies worldwide. This study systematically analyses the data in the literature on the use of SPOM and compares the outcomes to the original paper (Albuz et al. Hum. Rep., 25: 2999-3011 2010), classifying them into success or failure. The PubMed, Scopus, and Google Scholar databases were searched and 22 studies were included, from which data on 26 experiments were extracted and evaluated via descriptive statistical analysis. Only experiments that assessed the blastocyst rate (BR) were considered for the success parameter, i.e. success (increase in BR) or failure (either no difference or a reduction in BR). The experiments applied the SPOM system in the following species: cattle, sheep, goats, mice, mares and cats. Three experiments (3/26) could not be evaluated for success or failure, and of the remaining, 34.7% (8/23) succeeded in improving blastocyst production. More than two-thirds (69.2%, 18/26) of experiments were conducted in cattle; of those, 86.8% (13/15) used TCM-199 as the IVM media, and 22.2% did not use forskolin or IBMX modulators as indicated in the original study. Also, 27.7% (5/18) of the experiments in cattle used the same type and dose of FSH, and 22% (4/18) used the same protein source and concentration as indicated in the original study. All experiments conducted in mice (3) kept the parameters of the original study in terms of forskolin and IBMX doses and BSA and FSH concentrations, however, they removed cilostamide from IVM. Cilostamide was used during IVM in more than half (53.8%) of all experiments, but only in cattle and sheep. Considering oocyte and embryo assessments, six experiments assessed cAMP levels and most (5/6) of these observed an increase: in cattle (2), sheep (2), and mice (1). Ten experiments evaluated the effect of SPOM on nuclear maturation, and in 90% (9/10), the SPOM system was able to arrest meiosis (cattle, sheep and mice). Thirteen experiments evaluated the total cell number (cattle, mice and sheep), and six (6/13) showed an increase. Our findings clearly indicate difficulties in reproducing the SPOM system worldwide, demonstrating that the meiosis arrest is not sufficient to ensure successful SPOM application. They also suggest that the different supplements used in the IVM medium and/or their interaction with modulators for different durations may produce a significant bias that affects experimental success.

During the in vitro fertilization treatment, human chorionic gonadotrophin (hCG) is routinely used as a substitute for the natural endogenous LH surge during the final stage of oocyte maturation. However, it does not provide the FSH surge observed in the mid-cycle of the natural cycle. To date, whether the FSH surge can improve oocyte quality and pregnancy outcomes remains unknown. Randomized controlled trials comparing the following four trigger methods to conventional hCG were examined: GnRH agonist (GnRHa), kisspeptin, GnRHa plus hCG (dual trigger), and FSH plus hCG (FSH co-trigger). The results showed that the use of dual triggers was associated with a significantly higher number of retrieved cumulus-oocyte complexes (COCs) (weighted mean difference [WMD] 1.625, 95% CI 0.684-2.565), retrieved mature oocytes (WMD 0.986, 95% CI 0.426-1.545) and fertilized (2PN) oocytes (WMD 0.792, 95% CI 0.083-1.501), compared with the use of hCG. However, there was no significant difference between the two groups in terms of pregnancy rate. The FSH co-trigger resulted in significantly higher rates of 2PN oocytes retrieved than the hCG trigger (WMD 0.077, 95% CI 0.028-0.126). Notably, the risk of OHSS did not differ among the three treatment groups compared to that of the hCG group. This review protocol was registered with PROSPERO (CRD 42020194201).

OBJECTIVE: We report a successful live birth after oocytes in vitro maturation (IVM) and fresh embryo transfer in a patient with autoimmune premature ovarian failure (POF) and performed a review of the literature of livebirths obtained after oocytes IVM treatment in this indication.
METHODS: The patient was a 24-year-old woman with autoimmune POF diagnosed post-partum, who developed autoimmune polyglandular syndrome with serum anti-ovarian and anti-21-hydroxylase antibodies. The patient had typical symptoms of POF: secondary amenorrhea with hypoestrogenism, elevated gonadotropins and infertility; however, the serum anti-Müllerian hormone level and total antral follicle count remained normal. IVM of immature oocytes was performed after the administration of 150 IU highly purified human menopausal gonadotropin for three consecutive days and an injection of 10,000 IU human chorionic gonadotropin to trigger ovulation.
RESULTS: The six oocyte-cumulus complexes collected matured in vitro. After intracytoplasmic sperm injection (ICSI), five embryos were obtained. Pregnancy was achieved after the fresh transfer of two embryos and appropriate endometrial preparation. A normal female child was delivered following a 37-weeks pregnancy characterized by the onset of adrenal insufficiency and unstable diabetes.
CONCLUSIONS: We report a successful livebirth after IVM treatment in a patient with autoimmune premature ovarian failure (POF). Management of reproductive age women with autoimmune pathology requires fertility counseling. Early diagnosis of autoimmune POF is important for early conception and oocyte preservation, because the only other option at present is ovum donation.