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1.
Horm Mol Biol Clin Investig ; 29(2): 61-65, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27505093

RESUMO

BACKGROUND: The aim of this study was to analyze the alterations in thiol levels among mothers and neonates who were prone to medical oxytocin induction. MATERIALS AND METHODS: A total of 40 pregnant women who underwent medical labor induction with oxytocin (Group A) were compared with 53 women whose labor progressed spontaneously without any kind of induction (Group B). We measured the thiol/disulfide homeostasis parameters (native thiol, total thiol, disulfide, disulfide/total thiol, disulfide/native thiol) of maternal and cord blood. RESULTS: There were no statistically significant differences with respect to the maternal and cord blood thiol/disulfide homeostasis between the two groups. CONCLUSION: Being an artificial intervention during labor, oxytocin induction has been found to be safe in terms of oxidative stress (OS) according to the results of this study. Both the maternal and the fetal sides were safe in this molecular manner against oxytocin infusion.


Assuntos
Biomarcadores/sangue , Dissulfetos/sangue , Trabalho de Parto Induzido , Estresse Oxidativo , Ocitocina/administração & dosagem , Compostos de Sulfidrila/sangue , Adulto , Estudos Transversais , Feminino , Sangue Fetal/metabolismo , Homeostase , Humanos , Recém-Nascido , Ocitócicos/administração & dosagem , Gravidez , Estudos Prospectivos
2.
J Exp Ther Oncol ; 11(4): 269-273, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27849337

RESUMO

OBJECTIVE: To evaluate the association of the oxidative stress markers in patients with endometrial polyp. METHODS: A total of forty nine patients between 28-47 years of ages who have a suspect evidence of endometrial polyp on transvaginal sonography were enrolled for the study. Hysterosonography was applied all of the patients and patients then were divided into two groups in terms of their hysteroscopic findings. Group 1(control group, n=27) defined who has no endometrial pathology and group 2 (study group, n=22) defined has one or more endometrial polyp on hysteroscopy with guided biopsy. The diagnosis was established by histopathological examination polyps. The parameters compared between groups were; age, body mass index, catalase (CAT), xsantine oxidase (XO), malondialdehyde (MDA) levels. RESULTS: There were no statistically significant differences between groups in terms of age and BMI. Catalase, xsantine oxidase and malondialdehyde levels were statically significantly different between the groups (p < 0,05). The mean of polyp diameter size were 17.95 ±0.45 mm and the number of the polyp per patient was 1.54 ± 0.67. CONCLUSION: According to our study, serum catalase, xsantine oxidase and malondialdehyde levels may be discriminative parameters for patients with endometrial polyp.


Assuntos
Biomarcadores/metabolismo , Estresse Oxidativo/fisiologia , Pólipos/metabolismo , Pólipos/patologia , Doenças Uterinas/metabolismo , Doenças Uterinas/patologia , Adulto , Biópsia/métodos , Estudos de Casos e Controles , Catalase/metabolismo , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histeroscopia/métodos , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia/métodos
3.
J Assist Reprod Genet ; 32(11): 1659-68, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26404793

RESUMO

PURPOSE: Follicle-stimulating hormone (FSH) and its receptor play a major role in the development of follicles and regulation of steroidogenesis in the ovary and spermatogenesis in the testis. We aim to analyze the role of FSHR gene variants (single nucleotide polymorphisms (SNPs) in exon 10 (codon 307 and 680) and in the core promoter region (at position -29) and Ala189Val inactivating mutation) in Turkish infertile women. There were studies analyzing the effects of the SNPs in exon 10 (codon 307 and 680) and in the core promoter region (at position -29) of the FSHR gene on spermatogenesis, but to our knowledge, there were no studies analyzing the effects of these three SNP combinations on female fertility. METHODS: In this study, the allelic, genotype, and haplotype frequency distributions of these three SNPs in the FSHR gene were analyzed in 102 infertile women and 99 unrelated healthy control individuals. The distribution of the polymorphisms was conformed by Hardy-Weinberg equilibrium test. RESULTS: There were no statistical differences (P > 0.05) in the allele, genotype, and haplotype frequencies of the polymorphisms and FSH, luteinizing hormone (LH), estradiol (E2), and prolactin (PRL) levels between the infertile patients and the controls. However, a significant relation was found between 307 SNP GA genotype and FSH level ≥12. We did not find any homozygous or heterozygote mutations in infertile patients and healthy fertile controls. CONCLUSION: The present study was the first study analyzing gma mutation and the polymorphism of the FSHR core promoter at position -29 alone and in combination with the two common SNPs in exon 10 in Turkish infertile women population. These findings indicate the significance of Ala307Thr GA genotype may be a predictive marker for poor ovarian reserve and infertility.


Assuntos
Infertilidade Feminina/genética , Polimorfismo de Nucleotídeo Único , Receptores do FSH/genética , Adulto , Estudos de Casos e Controles , Códon , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/genética , Frequência do Gene , Haplótipos , Humanos , Infertilidade Feminina/sangue , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Mutação , Prolactina/sangue , Prolactina/genética , Regiões Promotoras Genéticas , Turquia
4.
J Low Genit Tract Dis ; 17(1): 71-4, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23222051

RESUMO

Proliferating trichilemmal tumor (PTT) is a rare but morphologically distinct tumor that usually arises on the scalp of elderly women. It is composed of multiple cysts consisting of squamous epithelium with trichilemmal keratinization without granular layer interposition. Vulvar proliferating trichilemmal cyst is very rare, with, to the best of our knowledge, only 3 cases previously reported in the literature. We describe a 39-year-old woman with recurrent PTT on the left labium majus of the vulva, which had been excised from the same side 5 years before. She had a palpable nodule, approximately 2 cm in size, which was firm, mobile, and nontender; without erythema and ulceration; and covered by normal skin on the vulva. There was no inguinal lymphadenopathy. The lesion was removed by wide surgical excision; because of the tissue elasticity, primary closure was possible. The pathology result was reported as proliferating trichilemmal carcinoma with tumor-free margins. Although local recurrence after wide excision is rare, we recommend complete excision for treatment of PTT and long-term follow-up because of the possibility of recurrence.


Assuntos
Cisto Folicular/diagnóstico , Cisto Folicular/patologia , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologia , Adulto , Progressão da Doença , Cisto Epidérmico , Feminino , Cisto Folicular/cirurgia , Doenças do Cabelo/cirurgia , Histocitoquímica , Humanos , Microscopia , Recidiva , Vulva/patologia , Neoplasias Vulvares/cirurgia
5.
J Reprod Med ; 58(11-12): 511-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24568046

RESUMO

OBJECTIVE: To determine the role of vitamin D for preventing or reducing postoperative adhesions. STUDY DESIGN: The uterine horn adhesion model was carried out in 24 female Wistar rats. The animals were randomized into 4 groups: (1) control, (2) Ringer's lactate, (3) olive oil, and (4) vitamin D. Adhesion grade and histologic findings of adhesion-carrying tissues were evaluated, and groups were compared according to these parameters. RESULTS: Rats treated with vitamin D had less adhesion and lower inflammation grade when compared to the control and Ringer's lactate groups, and the results were statistically significant (p < 0.05). On the other hand, no difference was detected between the groups according to the fibrosis score. CONCLUSION: Vitamin D decreased postsurgical adhesion scores by both visual scores and histologic analyses in a rat model. Further experimental and clinical trials are required to confirm these results.


Assuntos
Aderências Teciduais/prevenção & controle , Doenças Uterinas/prevenção & controle , Vitamina D/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Fibrose/patologia , Inflamação/patologia , Soluções Isotônicas/administração & dosagem , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Ratos , Ratos Wistar , Lactato de Ringer , Aderências Teciduais/patologia , Doenças Uterinas/patologia , Útero/patologia , Útero/cirurgia
6.
Arch Gynecol Obstet ; 286(6): 1597-600, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22865034

RESUMO

PURPOSE: To analyze the changes in the endometrial thickness in infertile polycystic ovary syndrome (PCOS) patients throughout an entire menstrual cycle and compare the changes to those seen in infertile patients without PCOS. METHODS: This prospective, cross-sectional study was conducted in a total of 58 non-obese, infertile women with PCOS. The endometrial thickness was measured at three different times throughout the menstrual cycle by ultrasound. Age- and body mass index (BMI)-matched control group consisted of 62 non-obese infertile patients without PCOS. Demographic, hormonal and the ultrasonographic measurements of the two groups were compared. RESULTS: Day 3 levels of LH were significantly different between the groups (p=0.013). Ovarian volume measurement was significant between the groups (p=0001). All the endometrial thickness measurements in the early, mid-cycle and late luteal phases were also significantly different; p=0.001 for all. CONCLUSION: The study demonstrated an increased endometrial stripe measurements throughout a menstrual cycle in infertile patients with PCOS, when compared to infertile patients without PCOS.


Assuntos
Endométrio/patologia , Infertilidade Feminina/patologia , Ciclo Menstrual , Ovário/patologia , Síndrome do Ovário Policístico/patologia , Adulto , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Estudos Transversais , Endométrio/diagnóstico por imagem , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Feminina/complicações , Hormônio Luteinizante/sangue , Tamanho do Órgão , Síndrome do Ovário Policístico/complicações , Estudos Prospectivos , Estatísticas não Paramétricas , Ultrassonografia , Adulto Jovem
7.
Arch Gynecol Obstet ; 285(6): 1753-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22294190

RESUMO

PURPOSE: Endometrial polyp is the commenest pathology among the structural uterine abnormalities. In this study we compared the IVF outcomes of patients who underwent hysteroscopic endometrial polyp excision with respect to the time interval between the polyp resection and the subsequent IVF cycle. MATERIALS AND METHODS: A total of 60 patients were divided into two groups according to the time interval between the hysteroscopic polyp resection and the start of the following IVF cycle. Of these, 29 patients had the IVF procedures <6 months after the polyp resection, whereas in 31 patients comprising the comparison group, IVF interventions were done ≥ 6 months after the resection. The IVF outcomes were compared. RESULTS: Differences in the mean number of retrieved oocytes, metaphase II (MII) oocytes and transferred embryos, ratios of MII oocytes, and G1, G2 and G3 embryo rates were insignificant between the groups (p > 0.05). The fertilization, implantation, and clinical pregnancy rates were also similar between the groups (p > 0.05). CONCLUSION: IVF outcomes seem to be unrelated to the time interval between the hysteroscopic polyp resection and the initiation of the IVF; the success rates may not be superior if the treatment is started in the first few months postoperatively.


Assuntos
Fertilização in vitro , Pólipos/cirurgia , Doenças Uterinas/cirurgia , Adulto , Transferência Embrionária , Feminino , Humanos , Recuperação de Oócitos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento
8.
J Assist Reprod Genet ; 29(4): 325-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22302530

RESUMO

PURPOSE: To determine Vit E effect on the treatment outcomes of women with unexplained infertility undergoing controlled ovarian stimulation and intrauterine insemination (IUI). METHODS: The study group (Group A, n053) underwent controlled ovarian stimulation with clomiphene citrate with Vit E administration, 400 IU/day p.o. while the control group(Group B, n050) underwent ovulation induction without VitE. Treatment outcomes were compared between the groups. RESULTS: There were no significant differences between the two groups with respect to the demographic outcomes. The difference in endometrial thickness on the day of hCG administration was significant between the two groups (p00.001).The effect of receiving Vit E on the implantation and the on going pregnancy rates were assesed Odds Ratio (OR) and corresponding 95% Confidence Intervals (CI). Receiving Vit E was not significantly associated with the implantation and the ongoing pregnancy rates; OR 0 1.22, 95% CI (0.44­3.4)and OR 0 1.43, 95% CI (0.49­4.1), respectively. CONCLUSION: Vit E administration may improve the endometrial response in unexplained infertile women via the likely antioxidant and the anticoagulant effects. It may also modulate the antiestrogenic effect of clomiphene citrate and the problem of a thin endometrium in these cycles may beadjusted


Assuntos
Implantação do Embrião/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação , Técnicas de Reprodução Assistida , Vitamina E/administração & dosagem , Adulto , Clomifeno/administração & dosagem , Feminino , Humanos , Folículo Ovariano/crescimento & desenvolvimento , Gravidez , Taxa de Gravidez , Resultado do Tratamento
9.
Eur J Obstet Gynecol Reprod Biol ; 161(1): 26-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22239939

RESUMO

OBJECTIVE: To study the arginase, nitric oxide synthase and nitric oxide pathways associated with passage of meconium. STUDY DESIGN: Cord blood samples were collected from 20 newborns with meconium-stained amniotic fluid (MSAF) and from 23 newborns with clear amniotic fluid. Cord blood pH, arginase, nitric oxide synthase and nitric oxide levels were compared between the groups. RESULT: The differences between the arginase and nitric oxide measurements of the newborns with MSAF and those with clear amniotic fluid were significant. In the MSAF group arginase levels were significantly lower (p=0.007) and nitric oxide levels were significantly higher (p=0.032) than the clear amniotic fluid group. CONCLUSION: Hypoxia may be involved in the pathogenesis of meconium passage due to decreased arginase and increased nitric oxide levels.


Assuntos
Líquido Amniótico/química , Arginina/metabolismo , Sangue Fetal/química , Mecônio , Adulto , Arginase/sangue , Feminino , Humanos , Hipóxia/complicações , Recém-Nascido , Óxido Nítrico/sangue , Óxido Nítrico Sintase/sangue , Gravidez
10.
Fertil Steril ; 97(1): 235-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22100168

RESUMO

OBJECTIVE: To compare the femoral cartilage thickness values of polycystic ovary syndrome (PCOS) patients with those of age-matched, healthy women and to find out whether cartilage thickness changes with the clinical parameters. DESIGN: A cross-sectional controlled study. SETTING: A secondary care center and a tertiary care center. PATIENT(S): Thirty-three women with PCOS (mean age: 23.7 ± 3.5 years; 66 knees) and 30 healthy control women matched for age and body mass index (mean age: 24.8 ± 4.2 years; 60 knees). INTERVENTION(S): Measurement of knee cartage thickness of infertile PCOS patients. MAIN OUTCOME MEASURE(S): The thickness of femoral articular cartilage measured with an ultrasound with a linear probe (7-12 MHz) as well as three midpoint measurements taken from each knee: the lateral condyle, intercondylar area, and medial condyle. RESULT(S): The demographic and clinical features of the PCOS patients, the laboratory evaluations, and the endometrial thickness values were recorded, and the three midpoint measurements were taken from each knee. The PCOS patients had thicker cartilage values than the control group at all measurement sites. There was no correlation between the clinical parameters and the cartilage thickness values of PCOS patients. CONCLUSION(S): Our findings support the possible favorable effects of estrogen and androgens in PCOS patients. However, our data cannot determine whether PCOS patients have less risk of developing osteoarthritis later in life because they also have higher BMI values. The possible long-term changes in cartilage thickness in PCOS patients require further study.


Assuntos
Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/etiologia , Cartilagem Articular/diagnóstico por imagem , Síndrome do Ovário Policístico/complicações , Ultrassonografia/métodos , Ultrassonografia/normas , Adulto , Estudos Transversais , Feminino , Fêmur/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Reprodutibilidade dos Testes , Adulto Jovem
11.
Balkan Med J ; 29(2): 197-200, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25206994

RESUMO

OBJECTIVE: The gonadotropin-releasing hormone-agonist (GnRH-a) treatment during in vitro fertilization (IVF) sometimes causes a functional ovarian cyst during the administration period before gonadotropin stimulation, as an undesired event. The aim of this study was to analyze the effect of these cysts on the IVF outcomes. MATERIAL AND METHODS: Out of 981 IVF cycles, 78 with ovarian cysts were retrospectively analyzed with respect to the demographic characteristics, hormonal outcomes, and fertilization, implantation and clinical pregnancy rates. RESULTS: The metaphase II oocyte ratio, fertilization rate and percentage of high quality embryos (grade 1) were significantly higher in the cyst-negative group (p<0.0001; p<0.0001; p≤0.05). These same three parameters were also significantly higher in the cyst-aspirated group (p<0.01; p<0.05; p<0.05). Cyst diameters of the aspiration group were significantly higher (p<0.05). No statistically significant differences in implantation and clinical pregnancy rates were determined between the groups. CONCLUSION: An ovarian cyst formation during the GnRH-a suppression period negatively affects oocyte quality. Cyst aspiration before gonadotropin stimulation does not improve the IVF outcome.

12.
Iran J Reprod Med ; 10(2): 155-60, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25242990

RESUMO

BACKGROUND: Prolonged GnRH-a administration in IVF cycles may have some advantages related to the treatment outcomes. OBJECTIVE: In this study, we aimed to analyse the effect of prolonged gonadotropin releasing hormone agonist (GnRH-a) administration on controlled ovarian hyperstimulation outcomes of in vitro fertilization (IVF) patients. MATERIALS AND METHODS: In this retrospective study, 55 patients with a GnRH-a administration period more than 10 days were compared with 55 patients whose same period was ≤10 days with respect to the demographic characteristics, metaphase II (MII) oocyte ratio, grade I (GI) embryo ratio, blastocyst ratio, fertilization, implantation, and the clinical pregnancy rates. RESULTS: The mean hospital visit count of the prolonged GnRH-a patients was 2.6±0.4. As we expected, total GnRH-a doses used during hypophyseal down regulation were significantly different between the groups (p<0.0001). MII oocyte, G1 embryo and the blastocyst ratios were also significantly different between the groups (p<0.0001; p<0.01 and p<0.05). All the other parameters were insignificant. CONCLUSION: Prolonged GnRH-a administration during ovarian suppression in IVF patients may have positive impacts on the oocytes and the embryos, but this affect may not be observed in the overall pregnancy rates.

13.
J Assist Reprod Genet ; 28(9): 815-20, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21748445

RESUMO

PURPOSE: We aimed to analyse the in vitro fertilization-embryo transfer (IVF-ET) outcomes of the patients with sleep disturbances who were administered melatonin. METHODS: A total of 60 patients with sleep disturbances were divided into two groups. The study group (group A, n=30) had underwent the IVF-ET with melatonin administration and the control group (group B, n=30) without melatonin. Sleeping status after melatonin administration and the IVF outcomes were compared between the two groups. RESULTS: Sleeping status change was not significant (p>0.05). The mean number of the retrieved oocytes, the mean MII oocyte counts, the G1 embryo ratio were significantly higher in the melatonin administered group (group A) than that the non-administered group (group B); p=0.0001; p=0.0001; p<0.05 respectively. CONCLUSION: IVF patients with sleep disorders may benefit from melatonin administration in improving the oocyte and the embryo quality, but the sleeping problem itself may not be fixed.


Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Embrião de Mamíferos/efeitos dos fármacos , Fertilização in vitro , Melatonina/farmacologia , Oócitos/efeitos dos fármacos , Transtornos do Sono-Vigília/tratamento farmacológico , Depressores do Sistema Nervoso Central/uso terapêutico , Transferência Embrionária , Embrião de Mamíferos/fisiologia , Feminino , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/tratamento farmacológico , Melatonina/uso terapêutico , Oócitos/fisiologia , Gravidez , Taxa de Gravidez , Transtornos do Sono-Vigília/complicações , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico
14.
Arch Gynecol Obstet ; 284(2): 385-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20844884

RESUMO

PURPOSE: The aim of our retrospective study was to assess and to compare the surgical complications of hysterectomy regarding the choice of procedure [abdominal (AH), vaginal (VH), and total laparoscopic hysterectomy (TLH)]. METHODS: A total of 6,480 patient charts undergone hysterectomy were retrospectively analyzed. Data including transfusion, bladder, ureteral and bowel injury, cuff dehiscence, pulmoner embolus, febrile morbidity, hematoma, reoperation, pelvic wall problems were gathered. The Chi-square test and Student's t test were used in the statistical analysis. RESULTS: The most common perioperative complication was blood transfusion which occurred in 114 patients (2.6%). VH patients required significantly less blood transfusion than AH (2.1, 2.6%, respectively). AH had significantly more bladder injury than VH (0.7, 0.4%, respectively). AH had significantly more ureteral injury than VH (0.2, 0.1%, respectively). AH had the same bowel injury as VH (0.1%). AH and VH necessitated significantly more reoperation than TLH (0.4, 0.2, 0.0%, respectively). CONCLUSION: To our study, VH ensures less complication rates than AH. In experienced centers, VH can be a reliable alternative to AH. Controlled prospective studies with large patient volumes are required to compare TLH and VH according to complication rates.


Assuntos
Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Adulto , Idoso , Transfusão de Sangue , Distribuição de Qui-Quadrado , Feminino , Humanos , Histerectomia/métodos , Histerectomia Vaginal/efeitos adversos , Tempo de Internação , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Ureter/lesões , Bexiga Urinária/lesões
15.
Iran J Reprod Med ; 9(2): 105-12, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-25587256

RESUMO

BACKGROUND: The intracytoplasmic sperm injection procedure ending with total fertilization failure is very distressfull event for both the clinician and the patient. OBJECTIVE: The aim of this study was to identify independent factors which could be used to identify total fertilization failure before the day of intracytoplasmic sperm injection. MATERIALS AND METHODS: This was a retrospective study of 232 patients who were admitted to a tertiary-care hospital IVF Unit and showed total fertilization failure during intracytoplasmic sperm injection cycles. To sort out the interwined effects of female age, basal FSH, sperm quality, antral follicle count, starting dose of gonadotrophine, sperm extraction technique, cycle length, >14 mm follicle number, oocyte number after oocyte pick up, estradiol and progesterone level on the day of hCG and the MI, MII and GV oocyte number on the fertilization, multiple logistic regression analysis was used. RESULTS: The total fertilization failure rate was 6% and the recurrance rate was 23%. The original model illustrated that the presence of GV oocytes, total oocyte number less than six, <2000 pg/mL E2 concentration on the day of hCG and testicular sperm extraction increases the total fertilization failure risk. CONCLUSION: It is very difficult to predict total fertilization failure. Sometimes even with one good quality oocyte and sperm and in the case of globozoospermia fertilization can be achieved. Not only azoospermia but also low oocyte numbers increase the chance of total fertilization failure even after intracytoplasmic sperm injection.

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