OBJECTIVE: To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment. METHODS: A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate. RESULTS: A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05). CONCLUSION The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.
Child ; Humans ; Male ; Female ; Pregnancy ; Azoospermia/genetics* ; Oligospermia/genetics* ; Incidence ; Chromosome Deletion ; Chromosomes, Human, Y/genetics* ; Semen ; Infertility, Male/genetics* ; Chromosome Aberrations ; Follicle Stimulating Hormone/genetics*

The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility, for example, follicle-stimulating hormone (FSH), testicular volume (TV), and testosterone (T), to better predict sperm retrieval rate (SRR). Twenty-nine studies were included, 9 with data on conventional testicular sperm extraction (cTESE) for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction (mTESE) for a total of 4760 patients. A weighted-means value of SRR, FSH, T, and TV was created, and a weighted linear regression was then used to describe associations among SRR, type of procedure, FSH, T, and TV. In this study, weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9% vs 40.1%. Multiple weighted linear regressions were created to describe associations among SRR, procedure type, FSH, T, and TV. The models showed that for every 1.19 mIU ml^-1 increase in FSH, there would be a significant decrease in SRR by 1.0%. Seeking to create a more clinically relevant model, FSH values were then divided into normal, moderate elevation, and significant elevation categories (FSH <10 mIU ml^-1, 10-19 mIU ml^-1, and >20 mIU ml^-1, respectively). For an index patient undergoing cTESE, the retrieval rates would be 57.1%, 44.3%, and 31.2% for values normal, moderately elevated, and significantly elevated, respectively. In conclusion, in a large meta-analysis, mTESE was shown to be more successful than cTESE for sperm retrievals. FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.
Humans ; Male ; Follicle Stimulating Hormone ; Follicle Stimulating Hormone, Human ; Infertility, Male ; Linear Models ; Semen ; Sperm Retrieval ; Spermatozoa ; Testis/surgery*

Objective: To assess the association of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility. METHODS: We searched Pubmed, EMBASE, Web of Science, CNKI, and WANFANG databases for literature on the correlation of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility published from 2005 to the present time. According to the inclusion criteria, we included 12 epidemiological case-control studies and subjected them to a comprehensive analysis with the Stata11.0 software. RESULTS: A total of 2 893 male infertility patients and 3 312 controls were involved in the 12 studies. The Thr307Ala (rs6165) gene polymorphism was shown to be a risk factor for male infertility among the three comparison models (homozygous comparison model, hybrid comparison model and dominant comparison model), with the pooled odds ratios (OR) of 1.26 (95% CI: 1.03－1.54, P = 0.023), 1.18 (95% CI: 1.03－1.36, P = 0.018), and 1.20 (95% CI: 1.05－1.37, P = 0.006), respectively. And the Asn680Ser(rs6166) polymorphism was a risk factor for male infertility in the homozygous comparison and recessive comparison models, with the pooled ORs of 1.24, (95% CI: 1.05－1.45, P = 0.009) and 1.20 (95% CI: 1.04－1.39, P = 0.013), respectively. Layered meta-analysis showed that in the homozygous comparison model, the Thr307Ala-Asn680Ser polymorphism is a risk factor for male infertility in the white population, with the OR of 1.37 (95% CI: 1.03－1.82, P = 0.003) and 1.21 (95% CI: 1.00－1.47, P = 0.048), respectively. CONCLUSIONS In the homozygous model (GG vs AA), the FSHRThr307Ala-Asn680Ser gene polymorphism might be a protective factor against male infertility.
Case-Control Studies ; Follicle Stimulating Hormone, Human ; genetics ; Homozygote ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Genetic ; Risk Factors

Objective: To analyze the clinical outcomes of repeated superovulation induction in patients with adenomyosis or moderate to severe pelvic endometriosis after failure in previous IVF-ET cycles with the ultra-long protocol. METHODS: We retrospectively analyzed the clinical data about 37 patients with adenomyosis or moderate to severe pelvic endometriosis in our center from 2009 to 2013, who underwent repeated IVF-ET after failure in the previous cycles with the ultra-long protocol, namely by injection of 2－6 ampoules of 3.75 mg gonadotropin-releasing hormone agonist (GnRH-a). All the patients met the following requirements: hCG-negative at 14 days after transfer, within 3－7 days after menstruation, and properly down-regulated serum follicle stimulating hormone (FSH) (<10 mIU/ml), luteinizing hormone (LH) (<10 mIU/ml), estradiol (E2) (<30 pg/ml), follicle diameter (<10 mm) and endometrial thickness, and received GnRH (Gonal-F, Serono) for ovulation induction. We compared the clinical and laboratory data and pregnancy outcomes between the first and repeated cycles before and after ovulation induction. RESULTS: The repeated cycles, as compared with previous ones, showed significant increases in the antral follicle count (AFC) on the first day of stimulation (7.55 ± 1.86 vs 6.45 ± 2.5, P<0.05), number of follicles =≥14 mm in diameter on the hCG trigger day (7.81 ± 3.6 vs 5.56 ± 3.68, P<0.05), level of E2 (［2 362.15 ± 1 210.49］ vs ［1 749.22 ± 1 139.44］ pg/ml, P<0.05), and numbers of oocytes retrieved (7.51 ± 3.23 vs 4.78 ± 3.41, P<0.05) and embryos transferred (2.00 ± 0.33 vs 1.50 ± 0.67, P<0.05), exhibited a remarkably reduction in the dose of GnRH (［1 791.65 ± 1 889.41］ vs ［3 439.56 ± 1 836.53］ IU, P<0.05), and achieved a clinical pregnancy rate of 62.16%. CONCLUSIONS With proper reduction of the FSH, LH and E2 levels and follicle diameter, repeated superovulation induction for IVF-ET can improve the ovarian response and pregnancy outcomes of the patients with adenomyosis or moderate to severe pelvic endometriosis after failure in the previous IVF-ET cycles with the ultra-long protocol.
Endometriosis ; blood ; Estradiol ; blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; blood ; Follicle Stimulating Hormone, Human ; blood ; Gonadotropin-Releasing Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Oocytes ; Ovarian Follicle ; Ovary ; Ovulation Induction ; methods ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Recombinant Proteins ; blood ; Retrospective Studies ; Superovulation

The need for simplified in-vitro fertilization (IVF) treatment approaches with the aim of reducing treatment burden and to prevent drop-outs after a failed IVF cycle can be met by the use of corifollitropin alfa for COS in association with a GnRH antagonist protocol. This is a report of the first local case of a successful pregnancy using corifollitropin alfa in IVF. This is a case of a 33 year-old G3 PO (0030) whose partner has teratozoospermia. COS using corifollitropin alfa yielded eight mature oocytes with no occurrence of OHSS. Six oocytes were fertilized using ICSI with six good quality embryos reaching cleavage stage. Two grade 1 embryos at day 3 cleavage stage were transferred. A clinical pregnancy was documented at 7 weeks age of gestation. Congenital anomaly scanning at 24 weeks age of gestation revealed a grossly normal fetus. Patient delivered a healthy, live, term baby boy. Review of literature suggests that corifollitropin alfa is as effective as rFSH in delivering live birth rate, ongoing pregnancy rate and clinical pregnancy rate. The sustained and higher FSH immunoreactivity concentrations and the inability for dose adjustment after treatment with a single dose of corifollitropin compared with the daily rFSH regimen underscores the need for careful patient selection in the use of corifollitropin alfa.

Human ; Male ; Adult ; Pregnancy Rate ; Follicle Stimulating Hormone, Human, With Hcg C-terminal Peptide ; Sperm Injections, Intracytoplasmic ; Teratozoospermia ; Fertilization In Vitro ; Oocytes ; Gonadotropin-releasing Hormone

OBJECTIVETo investigate the correlation between signal transducer and activator of transcription 3 (STAT3) expression and pituitary adenoma subtypes.

METHODThe STAT3 expression profiles in different pituitary adenomas from 74 patients were determined using quantificational real-time polymerase chain reaction,Western blot,and immunohistochemistry.

RESULTSExpression of STAT3 was observed in all pituitary adenoma subtypes. The STAT3 expression level was highest in growth hormone adenoma when compared with other tumors including prolactin,follicle-stimulating hormone/luteinizing hormone-secreting adenoma,and adrenocorticotrophic hormone-secreting adenoma. The follicle-stimulating hormone/luteinizing hormone adenomas exhibited the lowest STAT3 expression levels.

CONCLUSIONSTAT3 is differentially expressed in pituitary adenoma subtypes, suggesting the cell-specific features of STAT3 regulation,although further investigations are still warranted to clarify the underlying mechanisms.

Adenoma ; Follicle Stimulating Hormone ; Human Growth Hormone ; Humans ; Immunohistochemistry ; Pituitary Neoplasms ; Real-Time Polymerase Chain Reaction ; STAT3 Transcription Factor ; Signal Transduction

OBJECTIVE: To evaluate whether letrozole incorporated in a gonadotrophin-releasing hormone (GnRH) antagonist multiple dose protocol (MDP) improved controlled ovarian stimulation (COS) and in vitro fertilization (IVF) results in poor responders who underwent IVF treatment. METHODS: In this retrospective cohort study, a total of 103 consecutive IVF cycles that were performed during either the letrozole/GnRH antagonist MDP cycles (letrozole group, n=46) or the standard GnRH antagonist MDP cycles (control group, n=57) were included in 103 poor responders. COS results and IVF outcomes were compared between the two groups. RESULTS: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the letrozole group than in the control group. Duration of GnRH antagonist administered was also shorter in the letrozole group. The number of oocytes retrieved was significantly higher in the letrozole group. However, clinical pregnancy rate per cycle initiated, clinical pregnancy rate per embryo transfer, embryo implantation rate and miscarriage rate were similar in the two groups. CONCLUSION: The letrozole incorporated in GnRH antagonist MDP may be more effective because it results comparable pregnancy outcomes with shorter duration and smaller dose of rhFSH, when compared with the standard GnRH antagonist MDP.
Abortion, Spontaneous ; Aromatase* ; Cohort Studies ; Embryo Implantation ; Embryo Transfer ; Female ; Fertilization in Vitro* ; Follicle Stimulating Hormone, Human ; Gonadotropin-Releasing Hormone ; Humans ; Oocytes ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies

Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. The relatively short half-life of FSH in vivo requires daily injections for more than 10 days that is inconvenient and possibly contribute to the stress perceived by the patients. The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. The pcDNA3.1-FSH was linearized and transfected into CHO-K1, positive transformants were selected by G418 and confirmed by PCR and Western blotting. A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. The results suggested a long-acting FSH was produced successfully.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Female ; Follicle Stimulating Hormone, Human ; biosynthesis ; Genetic Vectors ; Half-Life ; Humans ; Ovarian Follicle ; drug effects ; Ovulation ; drug effects ; Rats ; Recombinant Proteins ; biosynthesis ; Transfection

OBJECTIVETo assess the value of combined evaluation of serum follicle-stimulating hormone (FSH), inhibin B (INHB), chromosome karyotyping and AZF microdeletion of Y-chromosome (AZF-MD-Ych) in predicting the success of testicular sperm aspiration (TESA) in azoospermic patients.

METHODSA total of 262 azoospermic patients were divided into two groups with normal (n=162) and abnormal (n=100) serum FSH levels. INHB levels, INHB/FSH ratio, chromosome karyotype patterns of the peripheral lymphocytes, and AZF-MD-Ych were compared between the two groups. Among the patients receiving TESA, the success rate of the procedure was compared between the two groups after excluding abnormalities in INHB, chromosome karyotype and AZF-MD-Ych.

RESULTSSignificant differences were found between the two groups in serum INHB level, INHB/FSH and chromosome karyotypes (P<0.05), but not in AZF-MD-Ych (P>0.05). After excluding the abnormalities in chromosome karyotypes, AZF-MD-Ych and INHB, sperms were obtained successfully by TESA from 61.82% (34/55) of patients with normal FSH but from none of those with abnormal FSH (P<0.01).

CONCLUSIONA combined evaluation of serum FSH, INHB, chromosome karyotypes and AZF-MD-Ych can effectively predict the success of TESA in azoospermic patients, and abnormalities in all the 4 indices suggest a very low success rate of sperm retrieval by TESA.

Azoospermia ; Chromosome Deletion ; Chromosomes, Human, Y ; Follicle Stimulating Hormone ; blood ; Humans ; Infertility, Male ; Inhibins ; blood ; Karyotyping ; Male ; Prognosis ; Sex Chromosome Aberrations ; Sex Chromosome Disorders of Sex Development ; Sperm Retrieval ; Spermatozoa ; Testis ; Treatment Outcome

OBJECTIVE: To evaluate the effect of the addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles for infertile patients undergoing IVF/ICSI. METHODS: One hundred and ten infertile patients, aged 28 to 39 years, were recruited for this prospective randomized study. They were randomly assigned to receive vaginal progesterone gel (Crinone) along with 4 mg estradiol valerate (group 1, n=55) or only Crinone (group 2, n=55) for luteal support. A GnRH antagonist multiple dose protocol using recombinant human FSH was used for controlled ovarian stimulation (COS) in all of the subjects. The COS results and pregnancy outcomes of the two groups were compared. RESULTS: Group 1 and 2 were comparable with respect to the patient characteristics. The COS and IVF results were also comparable between the two groups. There were no differences in the clinical pregnancy rate (PR) and multiple PR between the two groups. However, the embryo implantation rate were significantly higher in group 1 than that in group 2 (22.2% vs. 13.3%, p=0.035). The incidence of luteal vaginal bleeding (LVB) was significantly lower in group 1 (7.4% vs. 27.8%, p=0.010). CONCLUSION: The addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles reduces the incidence of LVB and increases the embryo implantation rate in infertile patients undergoing IVF/ICSI.
Aged ; Embryo Implantation ; Estradiol ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone, Human ; Gonadotropin-Releasing Hormone ; Humans ; Incidence ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Progesterone ; Prospective Studies ; Sperm Injections, Intracytoplasmic ; Uterine Hemorrhage