Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome? A multicenter study and systematic review of the literature.

STUDY QUESTION: Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome (TS)? SUMMARY ANSWER: The oocyte cryopreservation strategy is not well adapted for all TS women as their combination of high basal FSH with low basal AMH and low percentage of 46,XX cells in the karyotype significantly reduces the chances of freezing sufficient mature oocytes for fertility preservation. WHAT IS KNOWN ALREADY: An oocyte cryopreservation strategy requiring numerous stimulation cycles is needed to preserve fertility in TS women, to compensate for the low ovarian response, the possible oocyte genetic alterations, the reduced endometrial receptivity, and the increased rate of miscarriage, observed in this specific population. The validation of reliable predictive biomarkers of ovarian response to hormonal stimulation in TS patients is necessary to help practitioners and patients choose the best-personalized fertility preservation strategy. STUDY DESIGN, SIZE, DURATION: A retrospective bicentric study was performed from 1 January 2011 to 1 January 2023. Clinical and biological data from all TS women who have received from ovarian stimulation for fertility preservation were collected. A systematic review of the current literature on oocyte retrieval outcomes after ovarian stimulation in TS women was also performed (PROSPERO registration number: CRD42022362352). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 14 TS women who had undergone ovarian stimulation for fertility preservation were included, representing the largest cohort of TS patients published to date (n = 14 patients, 24 cycles). The systematic review of the literature identified 34 additional TS patients with 47 oocyte retrieval outcomes after ovarian stimulation in 14 publications (n = 48 patients, n = 71 cycles in total). MAIN RESULTS AND THE ROLE OF CHANCE: The number of cryopreserved mature oocytes on the first cycle for TS patients was low (4.0 ± 3.7). Oocyte accumulation was systematically proposed to increase fertility potential and was accepted by 50% (7/14) of patients (2.4 ± 0.5 cycles), leading to an improved total number of 10.9 ± 7.2 cryopreserved mature oocytes per patient. In the group who refused the oocyte accumulation strategy, only one patient exceeded the threshold of 10 mature cryopreserved oocytes. In contrast, 57.1% (4/7) and 42.9% (3/7) of patients who have underwent the oocyte accumulation strategy reached the threshold of 10 and 15 mature cryopreserved oocytes, respectively (OR = 8 (0.6; 107.0), P = 0.12; OR= 11 (0.5; 282.1), P = 0.13). By analyzing all the data published to date and combining it with our data (n = 48 patients, n = 71 cycles), low basal FSH and high AMH concentrations as well as a higher percentage of 46,XX cells in the karyotype were significantly associated with a higher number of cryopreserved oocytes after the first cycle. Moreover, the combination of low basal FSH concentration (<5.9 IU/l), high AMH concentration (>1.13 ng/ml), and the presence of 46,XX cells (>1%) was significantly predictive of obtaining at least six cryopreserved oocytes in the first cycle, representing objective criteria for identifying patients with real chances of preserving an adequate fertility potential by oocyte cryopreservation. LIMITATIONS, REASONS FOR CAUTION: Our results should be analyzed with caution, as the optimal oocyte number needed for successful live birth in TS patients is still unknown due to the low number of reports their oocyte use in the literature to date. WIDER IMPLICATIONS OF THE FINDINGS: TS patients should benefit from relevant clinical evaluation, genetic counseling and psychological support to make an informed choice regarding their fertility preservation technique, as numerous stimulation cycles would be necessary to preserve a high number of oocytes. STUDY FUNDING/COMPETING INTEREST(S): This research received no external funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

[Are gestational weight gain guidelines for obese women still appropriate?] / Les recommandations de prise de poids gestationnelle pour les femmes obèses sont-elles encore adaptées ?

Guidelines for adequate gestational weight gain were proposed in 2009 by the Institute of Medicine. In case of a BMI>30kg/m2, the recommended gestational weight gain should be between 5 and 9kg. However, these recommendations do not distinguish between different grades of obesity. Recent data suggest that the IOM recommendations are not restrictive enough for obese pregnant women and should be adapted to the grade of obesity.

[What issues, changes and adaptations for French ART centers in the context of the new bioethics law?] / Quels enjeux et adaptations pour les centres d'AMP dans le cadre de la mise en place de la nouvelle loi de bioéthique ?

OBJECTIVE: This review intends to introduce the changes of the new Bioethics law in the reproductive field and its application in French ART centers. MATERIAL AND METHODS: The review details the main provisions of the Bioethics Law of August 2nd 2021 as well as the three decrees published since: the first one on September 29th 2021, which specifies in particular the age conditions to benefit from ART and self-preservation of one's gametes; another decree on December 31st, 2021, to set the terms and conditions for gamete self-preservation activities for non-medical reasons and the last decree on April 14th 2022, relating to the allocation of donated gametes and embryo donation. RESULTS: Since the law of August 2nd, 2021, access conditions to assisted reproductive technology (ART) have evolved in France. Previously based on pathological infertility or the risk of transmission of a serious disease, ART is now intended to respond to the parental project of a couple formed by a man and a woman, two women or an unmarried woman. With the widening of access conditions, the use of gamete donation will likely increase. The upcoming raise of children born from gamete donation has led the legislator to question their right to access their origin. From September 1st 2022, adults born from gamete donation will be able to request a special administrative authority in order to access the donor's non identifying data (age, physical characteristics, family and professional situation, motivation for the donation…) and/or the donor's identity. Moreover, the new bioethics law opens up the possibility of autologous gamete cryopreservation without medical reasons, under specific age conditions, in order to carry out an assisted reproduction technique later. If gametes are not used, autologous gamete preservation could also allow an increase in gamete donation. However, the modification of gamete donation conditions could suggest a short term decrease in donors' number. Finally, the new bioethics law further opens up research on human embryos and embryonic stem cells. CONCLUSION: The arrangements introduced by the Bioethics Law promulgated on August 2nd, 2021 represent a major revolution in the field of Reproductive Medicine and are expected to transform the practices of reproductive biology centers and CECOS in France.

[HLA-C KIR interactions and placental defects: Implications in ART pregnancy issues]. / Interactions HLA-C KIR et anomalies de la placentation : implications dans les issues de grossesses obtenues en AMP.

OBJECTIVE: The aim of this review is to update data concerning the impact of HLA-C KIR system on placental disorders and assess the involvement on ART clinical outcomes. METHOD: Ensuring the maintenance of human pregnancy requires the set up of immunological tolerance to prevent foetus rejection. This phenomenon involves different actors of the immune system: among them, uterine NK cells (uNK) hold specific KIR (killer-cell immunoglobulin-like) receptors linking to HLA molecules on the surface of trophoblastic cells at implantation. Many studies provided evidence that the specific interaction between maternal KIR and foetal HLA-C could influence the process of placentation; according to the KIR haplotype and the type of HLA-C, the interaction could be detrimental for placental function. We reviewed the latest data available regarding HLA-C KIR interactions and ART outcomes. RESULTS: The available results highlight a significant increase of preeclampsia risk and recurrent miscarriages when the maternal inhibitory haplotype KIR AA is present, this risk is all the more enhanced when the interaction occurs with foetal HLA-C2. Recent data suggest the consequences of this detrimental interaction in case of DET (double embryo transfer) or use of donor's oocytes in ART practice. On the other hand, maternal KIR AB or BB haplotypes haven't been related to an additional obstetrical risk, as well as the foetal HLA-C1 homozygous allotype. CONCLUSION: Despite the existence of many confoundings in current literature on the subject, interaction between maternal KIR and foetal HLA-C represent a promising target lead to broaden the spectrum of placental defects etiologies, especially in the reproductive health area.

[Oncofertility and breast cancer at Montpellier University Hospital: Retrospective analysis of patients management since 2011]. / Oncofertilité et cancer du sein au CHRU de Montpellier : analyse rétrospective du devenir des patientes depuis 2011.

OBJECTIVE: Five to 7% of breast cancers affect women under 40 years old. The survival of these patients has been improved thanks to therapeutic advances, often to the detriment of their fertility. The objective of this study is to evaluate the activity of oncofertility and the future of young women with breast cancer managed at the Montpellier University Hospital. METHODS: This is a retrospective study including women aged from 18 to 43 years-old diagnosed with breast cancer and referred in oncofertility consultation at the Montpellier University Hospital between July 2011 and December 2018. RESULTS: 190 patients were eligible, three refused to participate to the study, hence 187 patients were included. We estimate that only 33% of young breast cancer patients potentially eligible for fertility preservation (FP) benefited from an oncofertility consultation in our region. Of these 187 patients, 58 (31%) underwent ovarian stimulation for oocyte or embryo vitrification. They were significantly younger: 32.9 vs 34.6 years old (P=0.01) and had fewer invaded lymph nodes. A total of 66 cycles were achieved and 11.4 oocytes or 3 embryos were vitrified per patient. The reuse rate was 3.6% with 91% of post cancer pregnancies being spontaneous. CONCLUSION: The oncofertility care network seems effective at the regional level. Enhancing health professionals' awareness and creating a regional register could improve our long-term follow-up.

[Natural cycle for frozen-thawed embryo transfer: Spontaneous ovulation or triggering by HCG]. / Transferts d'embryons congelés en cycle naturel : ovulation spontanée ou déclenchement par hCG ?

OBJECTIVE: To compare frozen-thawed embryo transfer (FET) outcomes in natural cycles according to ovulation induction: spontaneous versus recombinant human chorionic gonadotrophin (r-hCG) triggering. METHODS: This retrospective study included all patients monitored for natural cycle FET during one year. When serial monitoring were performed until spontaneous LH rise, patients were included in group A (n=38) whereas those receiving r-hCG for ovulation triggering formed group B (n=43). All embryos had been cryopreserved by a vitrification method following a previous IVF cycle. No luteal phase support had been given. We compared outcomes between the 2 groups. RESULTS: After checking groups comparability, we didn't find significant difference for the implantation rate, clinical pregnancy rate and live birth (31% vs 45%, 32% vs 51% et 21% vs 32%, respectively for group A and B). The number of monitoring was significantly lower in group B (1,9±0,8 versus 2,5±1, P=0,006). DISCUSSION: Although no consensus has been yet established, natural cycle seems indicated for normo-ovulating patients but the question of ovulation induction is still debated. In our study, triggering ovulation by r-hCG, respecting strict criteria, seems provide good results while reducing both protocol's constraints and cost.

[Poor responders: How could we improve our results?] / Mauvaises répondeuses : peut-on améliorer nos résultats ?

OBJECTIVES: Finding an efficient treatment for poor responders still poses a tremendous challenge for assisted reproductive technology. In 2011, an international consensus has been reached in Bologna on how to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. This article provides an objective assessment of the different treatment options currently available. METHODS: A search of the database PUBMED was carried out for studies published in English between October 2000 and April 2016. RESULTS: There is no ideal protocol to manage poor responders even though the antagonist protocol seems to have an advantage of clinicians. This is thanks to better patient tolerance and reduced total dose of gonadotrophin as well as shorter time of stimulation. It seems that there is no benefit in increasing the gonadotrophin daily doses over 300IU nor using any specific type of gonadotrophin. Today, there is insufficient evidence to recommend any additional treatment for poor responders. Only dehydroepiandrosterone (DHEA) seems to increase embryonic quality and pregnancy rate, however further exploration and complementary prospective studies are necessary. CONCLUSION: New treatment strategies such as "oocyte banking" or double stimulation during the same cycle, could provide new prospects in poor responders management.

[Circulating nucleic acids and infertility]. / Les acides nucléiques circulants et infertilité.

Circulating nucleic acids (cell-free DNA and microRNAs) have for particularity to be easily detectable in the biological fluids of the body. Therefore, they constitute biomarkers of interest in female and male infertility care. Indeed, in female, they can be used to detect ovarian reserve disorders (polycystic ovary syndrome and low functional ovarian reserve) as well as to assess follicular microenvironment quality. Moreover, in men, their expression levels can vary in case of spermatogenesis abnormalities. Finally, circulating nucleic acids have also the ability to predict successfully the quality of in vitro embryo development. Their multiple contributions during assisted reproductive technology (ART) make of them biomarkers of interest, for the development of new diagnostic and/or prognostic tests, applied to our specialty. Circulating nucleic acids would so offer the possibility of personalized medical care for infertile couples in ART.

Preimplantation genetic diagnosis for cystic fibrosis: the Montpellier center's 10-year experience.

This study provides an overview of 10 years of experience of preimplantation genetic diagnosis (PGD) for cystic fibrosis (CF) in our center. Owing to the high allelic heterogeneity of CF transmembrane conductance regulator (CFTR) mutations in south of France, we have set up a powerful universal test based on haplotyping eight short tandem repeats (STR) markers together with the major mutation p.Phe508del. Of 142 couples requesting PGD for CF, 76 have been so far enrolled in the genetic work-up, and 53 had 114 PGD cycles performed. Twenty-nine cycles were canceled upon in vitro fertilization (IVF) treatment because of hyper- or hypostimulation. Of the remaining 85 cycles, a total of 493 embryos were biopsied and a genetic diagnosis was obtained in 463 (93.9%), of which 262 (without or with a single CF-causing mutation) were transferable. Twenty-eight clinical pregnancies were established, yielding a pregnancy rate per transfer of 30.8% in the group of seven couples with one member affected with CF, and 38.3% in the group of couples whose both members are carriers of a CF-causing mutation [including six couples with congenital bilateral absence of the vas deferens (CBAVD)]. So far, 25 children were born free of CF and no misdiagnosis was recorded. Our test is applicable to 98% of couples at risk of transmitting CF.

[Effects of cigarette smoking on female reproduction: from oocyte to embryo (Part I)]. / Effets du tabagisme sur la reproduction : de l'ovocyte à l'embryon (Partie I).

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was to focus on the knowledge of the effects of cigarette smoking on all reproductive stages, from oocyte to embryo. For each reproductive functions human clinical and experimental studies were analysed in order to find hypothesis and explanations for effects observed. All reproductive functions are targets of smoke compounds and cigarette smoking impairs ovarian reserve, sexual steroids synthesis, Fallopian tubes functions and embryo development, leading to reduced fecundity. Some of smoke compounds were identified in ovarian tissue, in uterine fluid and in the embryo, suggesting direct toxicity.

[Effects of cigarette smoking on embryo implantation and placentation and analysis of factors interfering with cigarette smoke effects (Part II)]. / Effet du tabagisme sur l'implantation embryonnaire et la placentation précoce et facteurs influençant la toxicité tabagique sur la reproduction (Partie II).

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was first to focus on the knowledge of the effects of cigarette smoking on reproductive stages and particularly on implantation process and early placentation. Human clinical and experimental studies were analysed in order to find hypothesis and explanations for the effects observed. Then, our second aim was to analyse which factors could influence smoke effects. We observed that smoke compounds induce impairment of endometrial maturation, disturb angiogenesis and trophoblastic invasion. Cigarette compounds also impair uterine and endometrial vascularisation and myometrial relaxation. These effects lead to implantation failure in IVF and higher risk of miscarriage. Many factors influence the effects of cigarette smoke, as smoke behaviour, dose and duration of exposition. Sidestream is also damaging on reproductive function. Prenatal exposure leads to irreversible and deleterious effects on ovarian reserve. These observations need to be confirmed in order to improve health care in women of reproductive age.

Complex chromosomal rearrangements: origin and meiotic behavior.

BACKGROUND: Complex chromosomal rearrangements (CCRs) describe structural rearrangements, essentially translocations, involving at least three breakpoints on two or more chromosomes. Although they are rare in humans, their clinical identification is important since CCR carriers can display various phenotypes which include phenotypically normal subjects, infertile males and patients with mental retardation and/or congenital abnormalities. The rearrangement can be de novo or familial. The use of fluorescent in situ hybridization assays and molecular techniques for the characterization of CCRs have indicated that the rearrangements could be more complex than initially assumed. Accumulating data have revealed that the mechanisms underlying the genesis of CCRs remain elusive. METHODS: We performed a large PubMed search in order to summarize the current knowledge in this field and address important aspects of CCR formation and meiotic behavior, highlighting the complexity of these rearrangements at the chromosomal and genomic level. RESULTS: The review of published data indicates that the complexity of CCRs is becoming increasingly known, thanks to the application of more and more efficient molecular techniques. These approaches have allowed the precise sequence analysis of breakpoints and the identification of insertions, deletions, inversions and recombination events. New models have been proposed for the formation of CCRs, based on replication-based mechanisms and specific sequence elements. Their meiotic behavior has been discussed in the light of these new molecular data. CONCLUSIONS: Despite the increasing understanding of the mechanisms involved in their genesis, CCRs arise as unique, complex events for which the genetic and reproductive counseling of carriers remains a challenge.

Do female translocations influence the ovarian response pattern to controlled ovarian stimulation in preimplantation genetic diagnosis?

BACKGROUND: Ovarian response in female translocation carriers is not well understood. We aimed to evaluate the impact of chromosomal autosomal balanced translocations on the ovarian response to controlled ovarian stimulation (COS) in female carriers undergoing IVF and PGD. METHODS: In a retrospective study, we included all female translocation carriers who underwent PGD at our centre. We compared these patients to female patients from couples with male translocation carriers who underwent PGD. RESULTS: Results from 79 cycles of PGD from 33 female translocation carriers were compared with 116 cycles from 55 male translocation carriers. No difference was observed for patient characteristics: female age, anti-Müllerian hormone or antral follicle count. No difference in COS parameters was observed for the total dose of recombinant FSH, the number of retrieved oocytes and embryos on Day 3, for unaffected and transferred embryos. For the two groups, pregnancy rate was similar per cycle (12.7 versus 20.7%, P = 0.208). Multivariate analysis demonstrated that female translocation carriers had a significantly higher estradiol level on the day of hCG administration (+540 pg/ml, P = 0.05). CONCLUSIONS: This paper is the largest to report ovarian response of female translocation carriers. This study showed that the ovarian response to COS was not impaired by balanced translocation status, suggesting that female chromosomal structural abnormalities did not influence the results of COS in PGD. Thus, female carriers of balanced translocations could be considered normal responders and standard doses of gonadotrophins used for ovarian stimulation.

Effects of cigarette smoking on reproduction.

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

Predictive value of sperm-FISH analysis on the outcome of preimplantation genetic diagnosis (PGD) for a pericentric inversion inv5(p15.3q11.2) carrier.

BACKGROUND: Pericentric inversions (PIs) are structural chromosomal abnormalities, potentially associated with infertility or multiple miscarriages. More rarely, at meiosis, odd numbers of genetic recombinations within the inversion loop produce recombinant gametes which may lead to aneusomy of recombination in the offspring. METHODS: We report a FISH segregation analysis of an inv5(p15.3q11.2) carrier, both in sperm and blastomeres. In sperm, we directly evaluated the proportion of recombinant gametes and compared the results with chromosomal abnormalities found in blastomeres collected from embryos obtained following a preimplantation genetic diagnosis (PGD) procedure. RESULTS: A total of 7006 sperm nuclei were analyzed. The size of the inverted segment represented 27% of the total length of chromosome 5. The frequencies of balanced chromosomes (normal or inverted), recombinant chromosomes and unbalanced combinations were 97.1, 0.17 and 2.73%, respectively. Of six embryos, PGD FISH analysis revealed that one was a balanced embryo, whereas five were unbalanced and there were no recombinants. CONCLUSIONS: This study demonstrated the value of sperm-FISH analysis in providing reproductive genetic counseling for PI carriers. Our study also highlights the clinical relevance of performing PGD instead of prenatal diagnosis.

Myotonic dystrophy type 1 and PGD: ovarian stimulation response and correlation analysis between ovarian reserve and genotype.

This study aimed at evaluating parameters and results of ovarian stimulation for myotonic dystrophy type 1 (DM1) female patients undergoing preimplantation genetic diagnosis (PGD) and to assess an eventual association between genotype and ovarian reserve. A retrospective study involved all 17 DM1 patients treated in the study centre's PGD programme. The control group consisted of 22 patients treated for X-linked disorders in the same period. Comparative analysis of ovarian stimulation parameters and results was performed with bivariate and multivariate analysis. Then, among DM1 patients, a correlation between genotype (number of CTG repeats) and ovarian reserve, assessed by antral follicle count, was investigated. Comparative study showed no difference concerning the number of oocytes, embryos and pregnancy rate between the two groups. Multivariate analysis demonstrated that DM1 patients needed a significantly higher dose of gonadotrophins (+544IU, P<0.001) than X-linked disorders patients and suggests a decreased ovarian sensitivity. However, with higher dose of gonadotrophins, PGD for DM1 offers good reproductive outcomes with a clinical pregnancy rate of 35.7%. Genotype was not correlated to ovarian reserve and appeared not to be helpful for the choice of the dose of gonadotrophins.

Combined FISH and PRINS sperm analysis of complex chromosome rearrangement t(1;19;13): an approach facilitating PGD.

Complex chromosome rearrangements (CCRs) are structural aberrations involving three or more breakpoints on two or more chromosomes. These CCRs result in a high rate of chromosome imbalances potentially leading to subfertility and congenital abnormality. In this study, we analysed meiotic segregation in the sperm of a patient with a familial CCR 46, XY,t(1;19;13)(p31;q13.2;q31)mat included in an intracytoplasmic sperm injection program because of oligoasthenozoospermia. The rearrangement was first identified using conventional and molecular cytogenetic methods. Primed in situ labelling (PRINS) and fluorescence in situ hybridization (FISH) techniques were then combined allowing the simultaneous use of five fluorochromes on the same sperm preparation, for the segregation analysis and the evaluation of the reproductive options for this patient. Segregation analysis was performed in a total of 1822 sperm nuclei from the translocation carrier. The percentage of unbalanced sperm was 75.9%, including 34.1% from 3:3 segregation, 38.2% from 4:2 segregation, 3.5% from 5:1 segregation and 0.05% from 6:0 segregation. Only 14.8% of sperm nuclei were consistent with a normal or balanced chromosome complement. In conclusion, chromosome segregation analysis combining FISH and PRINS was performed in sperm from a CCR carrier using five fluorochromes. These results advance our understanding of the mechanisms of meiotic segregation, and facilitate the assessment of the usefulness of preimplantation genetic diagnosis procedures in CCR couples.

The cell cycle control protein cdc25C is present, and phosphorylated on serine 214 in the transition from germinal vesicle to metaphase II in human oocyte meiosis.

Cdc25C is a dual specificity phosphatase essential for dephosphorylation and activation of cyclin-dependent kinase 1 (cdk1), a prerequisite step for mitosis in all eucaryotes. Cdc25C activation requires phosphorylation on at least six sites including serine 214 (S214) which is essential for metaphase/anaphase transit. Here, we have investigated S214 phosphorylation during human meiosis with the objectives of determining if this mitotic phosphatase cdc25C participates in final meiotic divisions in human oocytes. One hundred forty-eight human oocytes from controlled ovarian stimulation protocols were stained for immunofluorescence: 33 germinal vesicle (GV), 37 metaphase stage I (MI), and 78 unfertilized metaphase stage II (MII). Results were stage dependent, identical, independent of infertility type, or stimulation protocol. During GV stages, phospho-cdc25C is localized at the oocyte periphery. During early meiosis I (MI), phosphorylated cdc25C is no longer detected until onset of meiosis I. Here, phospho-cdc25C localizes on interstitial microtubules and at the cell periphery corresponding to the point of polar body expulsion. As the first polar body reaches the periphery, phosphorylated cdc25C is localized at the junction corresponding to the mid body position. On polar body expulsion, the interior signal for phospho-cdc25C is lost, but remains clearly visible in the extruded polar body. In atresic or damaged oocytes, the polar body no longer stains for phospho-cdc25C. Human cdc25C is both present and phosphorylated during meiosis I and localizes in a fashion similar to that seen during human mitotic divisions implying that the involvement of cdc25C is conserved and functional in meiotic cells.