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    Can in vitro maturation overcome cycles with repeated oocyte maturation arrest? A classification system for maturation arrest and a cohort study
    (Wiley, 2021) Hatirnaz, Safak; Basbug, Alper; Hatirnaz, Ebru; Tannus, Samer; Hatirnaz, Kaan; Bakay, Kadir; Dahan, Michael H.
    Objective To investigate the role of gonadotropin-stimulated and human chorionic gonadotropin (hCG) -primed in vitro oocyte maturation (IVM) in cases of repeated in vitro fertilization (IVF) failure due to various forms of oocyte maturation arrest (OMA). Methods Retrospective cohort study. Results In all, 63 women with IVF failure due to OMA were evaluated in this study. According to the Hatirnaz & Dahan classification, 11 (17.5%) women were OMA type 1, 22 (34.9%) were OMA type 2, 0 were OMA type 3, 11 (17.5%) were OMA type 4, and 19 women were OMA type 5 (30.1%). Fewer oocytes were retrieved in the IVM than in the IVF cycles. No embryos were produced from oocytes collected in the IVM cycles of women with OMA types 1, 2, and 4. In the OMA type 5 group, 9 (47.4%) day 2 embryos and 6 (31.6%) day 3 embryos were obtained. The difference between the groups was statistically significant (P = 0.001, P = 0.002, respectively). Single day 3 embryo transfer was performed for the six patients with OMA type 5 but no clinical pregnancies occurred. Conclusions Follicle-stimulating hormone-stimulated and hCG-primed IVM does not improve oocyte maturation, developmental potential, or pregnancy rates of women with OMA. Future studies directed to re-establishing normal cytoskeletal architecture and machinery, and resumption of meiosis may be beneficial for obtaining mature oocytes.
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    A Comparison of Triple and Double Sperm Washing for Density Gradient Preparation in Intrauterine Insemination Cycles when Overnight Incubation of Specimens Occurred: A Retrospective Cohort
    (Imr Press, 2022) Soyer-Çalışkan, Canan; Hatirnaz, Kaan; Çelik, Samettin; Başbuğ, Alper; Hatirnaz, Ebru S.; Hatırnaz, Şafak; Dahan, Michael H.
    Background: The number of sperm washes to maximize outcomes for intra-uterine insemination has not been well investigated. Therefore, we undertook to compare the pregnancy and live birth rates of triple sperm washing and double sperm washing for density gradient preparation for intrauterine insemination (IUI) cycles. Methods: A retrospective cohort study including 279 couples (136 couples with triple sperm washing and 143 couples with double sperm washing) with a diagnosis of unexplained infertility and mild male subfertility who had IUI cycles between April 2015 and April 2017 were evaluated. After overnight incubation of the sperm, subjects underwent either traditional double sperm washing or Triple sperm washing which consists of use of a third gradient and spinning procedure to the conventional double gradient sperm washing in order to obtain a higher quantity of motile sperm. Results: Total sperm count after triple washing was higher than double sperm washing (98.25 +/- 62.06 vs. 81.08 +/- 31.57; p = 0.003). Positive beta-hCG test and live birth per cycle were higher in triple sperm washing (25.8% vs. 13.3%, p = 0.009; 18.4% vs. 9.8%, p = 0.039; respectively) than in the double sperm washing group. Conclusions: The use of motile sperms obtained from triple sperm washing may increase the rates of pregnancy and live birth in IUI cycles of women with unexplained and mild male factor infertility. A prospective randomized study should be undertaken to confirm the results.
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    Outcomes of random start versus clomiphene citrate and gonadotropin cycles in occult premature ovarian insufficiency patients, refusing oocyte donation: a retrospective cohort study
    (Taylor & Francis Ltd, 2018) Hatırnaz, Şafak; Başbuğ, Alper; Akarsu, Süleyman; Hatırnaz, Ebru; Demirci, Hakan; Dahan, Michael H.
    The aim of this study is to present the clinical outcomes of a random start, a spontaneous folliculogenesis protocol versus Clomiphene Citrate and Gonadotropin treatment in women with occult premature ovarian insufficiency. Women underwent treatment between 1 February 2009, and 30 May 2016. 41 women were treated with the random start protocol while 48 cases received ovarian stimulation with clomiphene and gonadotropins. All included cases met the criteria of 4 months of oligo-ovulation, follicular-stimulating hormone levels over 30 IU/L and anti-Mullerian hormone levels below 0.30 ng/mL. The random start protocol involved following the subjects for up to 6 months until spontaneous folliculogenesis occurred. The mean number of oocytes collected, mature oocytes, fertilized oocytes, and grade II embryos were significantly higher in the random start protocol (p < .05). The doses of gonadotropin administration and hCG were significantly lower in the random start protocol (p < .05). The clinical pregnancy and live birth rates were significantly higher in the random start protocol (p < .05). Likely stimulation is of little benefit in women with occult premature ovarian insufficiency. Observation while waiting for spontaneous folliculogenesis results in better outcomes, and less oocyte collections.
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    PROOF OF CONCEPT OF A TREATMENT FOR HUMAN OOCYTE MATURATION ARREST;TRANSVAGINAL OVARIAN NEEDLE INJURY PRECEEDING LETROZOLE PRIMING IN VITRO MATURATION
    (Elsevier Science Inc, 2020) Hatirnaz, Safak; Hatirnaz, Ebru; Basbug, Alper; Dahan, Michael H.; Hatirnaz, Kaan
    [Abstract Not Available]
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    TUBB8 mutations as a cause of oocyte maturation abnormalities: presentation of oocyte and embryo profiles and novel mutations
    (Elsevier Sci Ltd, 2023) Ebru, Hatirnaz; Dahan, Michael H.; Sezer, Ozlem; Basbug, Alper; Kaan, Hatirnaz; Gungor, Nur Dokuzeylul; Baltaci, Volkan
    Research question: What are the embryonic profiles and oocyte maturation dynamics in patients with tubulin beta eight class VIII (TUBB8) mutations leading to oocyte maturation abnormalities (OMAS), and are pregnancies possible in this population?Design: A prospective cohort study was undertaken in a private fertility clinic between January 2019 and December 2022. Whole-exome genomic studies (WES) were performed to detect mutation types. In-vitro maturation (IVM) was compared in 18 subjects: nine with TUBB8 mutations, and nine without TUBB8 mutations to act as the control group. The distributions of oocyte maturation and embryonic development profiles were recorded. IVF and IVM outcomes of the 18 cases were evaluated. The primary outcomes were the embryonic profiles and maturation dynamics of oocytes derived from IVF or IVM in women as related to TUBB8 mutations.Results: Mutations were detected in 52 of 89 (58.4%) women who underwent WES analysis. Twelve TUBB8 mutations were detected in nine women (10.1%) with OMAS. Seven novel TUBB8 mutations were noted. Two pregnancies were obtained in women with c.535 G>A TUBB8 mutations. When comparing IVM outcomes between women with and without TUBB8 mutations, there were no differences in oocyte, embryo or pregnancy parameters (P>0.05 in all cases).Conclusions: It is clear that further TUBB8 mutations which cause oocyte or embryonic arrest will be detected in future. Although biochemical or ectopic pregnancies may be possible in some of these women, no live births or ongoing pregnancies have been reported to date.