Disordered hypothalamus-pituitary-ovary axis in heterotopic extraovarian sex cord-stromal proliferation: a case report of fallopian tube serous adenofibroma.

BACKGROUND: Fallopian tube serous adenofibromas are uncommon tumors of the female genital tract, only dozens of cases have ever been reported. Earlier study indicated that they might be derived from embryonic remnants of the Müllerian duct. Clinical presentation of these tumors is usually asymptomatic. Small cysts of 0.5-3 cm in diameter are mostly incidentally found at the fimbriae end, with coarse papillary excrescences lined by epithelial cells and connective tissue stroma without nuclear pleomorphism or mitosis. CASE PRESENTATION: A 23-year-old woman with normal secondary sexual characters and 46, XX karyotype, presented to the gynecology clinic complaining of irregular menstrual cycles. Laboratory studies reported unique discrepancy of hormone levels; anti-Müllerian hormone (AMH): 6.05 ng/mL (The normal range of AMH is 1.70-5.63 ng/mL in women aged under 35 years old), follicle stimulating hormone (FSH): 31.9 mIU/mL (reference range: 3.85-8.78, follicular phase; 4.54-22.51, ovulatory phase; 1.79-5.12, luteal phase; 16.74-113.59, menopause), and luteinizing hormone (LH): 52.0 mIU/mL (reference range: 2.12-10.89, follicular phase; 19.18-103.03, ovulatory phase; 1.20-12.86, luteal phase; 10.87-58.64, menopause), mimicking gonadotropin-resistant ovary syndrome. The ultrasound reported a right adnexal cyst of 10.4 × 7.87 × 6.7 cm. Laparoscopic evaluation was performed; pathology revealed serous adenofibroma of the fallopian tube with ovarian stroma contents. Heterotopic extraovarian sex cord-stromal proliferations was most probable. The patient's hormone levels returned to the reproductive status two weeks after surgery; FSH: 7.9 mIU/mL, LH: 3.59 mIU/mL,and AMH: 4.32 ng/mL. The patient's menstrual cycles have resumed to normal for over two years after removal of the fallopian tube cyst. CONCLUSIONS: This case of fallopian tube serous adenofibromas presented a discrepancy of serum AMH and FSH mimicking gonadotropin-resistant ovary syndrome. The clinical picture derived from heterotopic extraovarian sex cord-stromal proliferation indicated a disordered hypothalamus-pituitary-ovary axis.

Intraovarian Injection of Recombinant Human Follicle-Stimulating Hormone for Luteal-Phase Ovarian Stimulation during Oocyte Retrieval Is Effective in Women with Impending Ovarian Failure and Diminished Ovarian Reserve.

It is a challenge to obtain sufficient eggs during in vitro fertilization (IVF) in women with impending ovarian failure (IOF)/diminished ovarian reserve (DOR). Although studies have suggested that more than one wave of follicle growth exists, the efficacy of controlled ovulation stimulation (COS) in both follicular and luteal phases of the same ovarian cycle (DuoStim) is not established in women with IOF/DOR. We investigated the efficacy of DuoStim using the intraovarian injection of recombinant human follicle-stimulating hormone (rhFSH) during oocyte retrieval in women with DOR. For luteal-phase stimulation, intraovarian (Group A, N = 28) or superficial subcutaneous (Group B, N = 18) injection of 300 IU rhFSH immediately after oocyte retrieval was administered as the first dose, and intermittent superficial subcutaneous addition of gonadotropins was employed accordingly for further COS in both groups. In Group A, significantly lower Gn doses, a shorter duration of COS, a greater number of antral follicle counts, and an increased number of retrieved mature and total oocytes were noted. Compared with the clinical outcomes of luteal-phase COS, the average daily doses of rhFSH used in Group A were significantly lower. In summary, the novel approach using intraovarian rhFSH injection provides an efficient treatment regimen in women with IOF/DOR.

Ovarian Follicular Growth through Intermittent Vaginal Gonadotropin Administration in Diminished Ovarian Reserve Women.

It is a challenge to obtain enough oocytes during in vitro fertilization (IVF) in women who have a poor ovarian response (POR) in achieving conception. We have adopted the characteristics of the first uterine pass effect, which we pioneered in employing the vaginal administration of gonadotropins in women receiving IVF treatments. In our previous study employing vaginal administration, faster absorption and slower elimination of gonadotropins were demonstrated, and, female subjects presented proper ovarian follicle growth and pregnancy rates. In this study, during 2016-2020, 300 to 675 IU of gonadotropins were administered vaginally every three days in 266 POR women for their controlled ovarian hyperstimulation (COH). The injections were performed with needles angled at 15-30° towards the middle-upper portions of the bilateral vaginal wall, with an injection depth of 1-2 mm. For the COH results, these women, on average, received 3.0 ± 0.9 vaginal injections and a total dose of 1318.4 ± 634.4 IU gonadotropins, resulting in 2.2 ± 1.9 mature oocytes and 1.0 ± 1.2 good embryos. Among these embryos, 0.9 ± 1.0 were transferred to reach a clinical pregnancy rate of 18.1% and a live birth rate of 16.7%. In conclusion, the intermittent vaginal administration of gonadotropins proved to be effective in POR women for their IVF treatments.

Bacterial colonization at caesarean section defects in women of secondary infertility: an observational study.

BACKGROUND: Delayed childbearing has been noted in a high percentage of women with a previous Caesarean section (CS). Many women with CS scar defects (CSDs) present with clinical symptoms of irregular vaginal bleeding. The present study aimed to investigate bacterial colonies at CSDs in women suffering from secondary infertility. METHODS: This observational study included 363 women with secondary infertility who visited the Assisted Reproduction Unit between 2008 and 2013. Among them, 172 women with a previous CS and 191 women with no previous CS were approached. The women with a previous CS had their CS operations in the past 1 to 14 years, with a mean of 3.5 years. The presence of CSDs was detected by vaginal ultrasonography. Bacteriology cultures of specimens taken from the uterine niches in those with CSDs were collected during Day 7 to Day 10 of the follicular phase. Specimens were obtained from the endocervical canal for bacterial culture in those without CSDs. The main outcome measure was the detection of the growth of bacterial colonies. RESULTS: CSDs were found in 60.4% (96 of 159) of women with a previous CS. In women with a previous CS, bacterial colonies were identified in 89.6% (86 of 96) and 69.8% (44 of 63) of women with and without CSDs, respectively. In women with no previous CS, 49.7% (88 out of 177) of bacterial cultures of endocervical samples showed bacterial colony growth. Gram-positive cocci (P = 0.0017, odds ratio (OR) = 1.576, 95% confidence intervals (CI) -22.5 to - 5.4) and Gram-negative rods (P = 0.0016, OR = 1.74, CI - 20.8 to - 5.0) were the most commonly isolated bacteria and contributed to approximately 90% of all microorganisms found in those with a previous CS. In women with a previous CS, more Gram-negative rods were isolated (P = 0.01, OR = 1.765, CI - 27.2 to - 3.8), especially Pseudomonas species (P = 0.02, OR = 1.97, CI - 16.7 to - 1.0), in those with visible CSDs than in those without CSDs. CONCLUSIONS: Bacterial colonization at CSDs was found in a high percentage of women with secondary infertility.

Extended Injection Intervals of Gonadotropins by Intradermal Administration in IVF Treatment.

CONTEXT: Gonadotropins can be administered every 5 days under intradermal injection in in vitro fertilization (IVF) treatment. OBJECTIVE: To explore the effectiveness of intradermal injection of recombinant human FSH (rhFSH) for women undergoing IVF. METHODS: Women who received their first IVF treatment enrolled in this prospective intervention in 2018. All women received a bolus of 900 IU rhFSH intradermally at day 2 of the treatment cycle followed by additional dosage of rhFSH at day 7 and/or day 10. The main outcome measures included the total dose of rhFSH and number of injections required, sequential serum FSH level detected, and number of mature oocytes retrieved. RESULTS: Seventy women completed the study. On average, 2.31 ±â€…0.73 injections and 1662 ±â€…397 IU of rhFSH were administered. While the baseline FSH level was 5.6 ±â€…2.2 IU/L, the serum concentrations of FSH after rhFSH administration were 35.3 ±â€…7.0 on the first day (24 hours) and 10.7 ±â€…3.7 IU/L on the fifth day (120 hours). A total of 10.5 ±â€…6.6 mature oocytes were retrieved, resulting in 7.3 ±â€…5.1 pronuclear embryos; 1.8 ±â€…0.6 embryos were transferred to the uterus. Our findings resulted in 72% fertilization, 91% cleavage, 31% implantation, and 36% live birth rates. Although fewer larger follicles were found, noninferiority results were noted in the mature oocytes retrieved, good embryos available, and clinical pregnancy rate compared with those received conventional daily subcutaneous rhFSH administration. CONCLUSION: Intradermal administration of rhFSH, with a smaller dose of rhFSH and fewer injections, may achieve the goal of a cost-effective and more patient-friendly regimen.

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats.

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.

Dasatinib-induced chylothorax in a patient with chronic myeloid leukaemia: a case report and literature review.

Dasatinib is a potent and effective second-generation oral tyrosine kinase inhibitor that is clinically indicated for the treatment of imatinib-resistant or imatinib-intolerant breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukaemia (CML) or for Philadelphia chromosome-positive acute lymphocytic leukaemia. The most common adverse events associated with dasatinib therapy are skin rash, gastrointestinal upset, pancytopenia, pulmonary hypertension, and fluid retention, including pleural effusion. However, chylothorax secondary to dasatinib administration has rarely been reported. Although the underlying mechanism leading to dasatinib-induced chylothorax is uncertain, the preferred treatment options are usually supported with diuretics or systemic steroids. Moreover, the discontinuation of the drug is mandatory in refractory cases. Here, we present the case of a patient with dasatinib-induced chylothorax, and review the previously reported cases in the literature.

Resumed ovarian function and pregnancy in early menopausal women by whole dimension subcortical ovarian administration of platelet-rich plasma and gonadotropins.

OBJECTIVE: This study was designed to investigate if whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin, in proximity to most ovarian follicles, is effective in restoring ovarian functions in women during early menopause. METHODS: Platelet-rich plasma, prepared from 40 mL of autologous peripheral blood using the buffy coat method, was injected into extended subcortical area of bilateral ovaries along with recombinant follicle-stimulating hormone (rFSH) (Gonal-F 300IU) under laparoscopic guidance. The posttreatment ovarian folliculogenesis and serum levels of FSH, luteinizing hormone (LH), and estradiol were followed up for 6 months at weekly to monthly intervals. IVF was carried out in women resuming ovulatory functions. RESULTS: Twelve early menopausal women with mean age of 44.42 ±â€Š2.84 were enrolled. After treatment, 11 women resumed their menstrual period in 37.1 ±â€Š23.5 days. Their average serum FSH was 70.47 ±â€Š20.92 and 26.22 ±â€Š17.55 IU/L, luteinizing hormone was 34.81 ±â€Š11.86 and 14.3 ±â€Š12.8 IU/L, before and after treatment, respectively. The mid-cycle E2 was 251.1 ±â€Š143.8 pg/mL. Ten oocyte retrievals were carried out among six participants, four of them received controlled ovarian stimulation and another two using natural ovulation cycles. Thirteen mature eggs were retrieved which were then ICSI fertilized to obtain 10 normally fertilized 2PN oocytes. Two participants had cleavage stage embryos transferred of which one achieved clinical pregnancy. CONCLUSIONS: Whole dimension subcortical ovarian administration of platelet-rich plasma with gonadotropin was shown to restore ovarian functions, at least temporarily, and could increase the probability of pregnancy using autologous oocytes in women with early menopause.

Live Birth in Woman With Premature Ovarian Insufficiency Receiving Ovarian Administration of Platelet-Rich Plasma (PRP) in Combination With Gonadotropin: A Case Report.

The conception rates among women with premature ovarian insufficiency (POI) remain extremely low. To achieve a successful pregnancy, most of these women have to receive donor oocytes through IVF treatment. Ovarian administration of platelet-rich plasma (PRP) has been recently applied to enhance the ovulatory function in women with poor ovarian response. However, no live birth has been reported for this application in patients with POI. In this study, we present a 37-year-old woman with POI who had secondary amenorrhea for 6 months. The clinical manifestations and evaluation of this women with a diminished ovarian function were an undetectable serum level of AMH (<0.02 ng/mL) and an elevated serum level of FSH (63.65 mIU/mL). A single dose of autologous PRP (extracted from 40 mL of peripheral blood) in combination with gonadotropin (150IU rFSH/75 IU rLH) was directly injected into the stroma of bilateral ovaries via vaginal sonographic guidance. Following the treatment, this patient received controlled ovarian stimulation and IVF during the successive months. Following embryo culture, three cleavage-stage embryos were transferred, leading to a successful pregnancy, which later resulted in the live birth of twins. This case report provides one example of alternative therapy that allows POI patients to use autologous oocytes in IVF treatment.

Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells.

SEPTIN12 (SEPT12) is a testis-enriched gene that is downregulated in the testis of infertile men with severe spermatogenic defects. While SEPT12 is involved in spermatogenic failure and sperm motility disorder, SEPT12 transcriptional regulation is still unknown. Here we report the promoter region of SEPT12 as a 245 bp segment upstream of the transcription start site. One androgen receptor (AR) and two estrogen receptor α (ERα) binding sites in this region were initially identified by bioinformatics prediction and confirmed by chromatin immunoprecipitation assay. Truncated ERα or AR binding sites decreased the promoter activity, which indicated that the ERα and AR are essential for the SEPT12 promoter. On the other hand, the promoter activity was enhanced by the treatment with 17ß-estradiol (E2) and 5α-dihydrotestosterone (5α-DHT). Thus, one androgen and two estrogen hormone responsive elements located in the promoter of SEPT12 gene can regulate SEPT12 expression. Two single nucleotide polymorphisms (SNPs), rs759992 T > C and rs3827527 C > T, were observed in the SEPT12 gene promoter region and were able to decrease the promoter activity. In conclusion, the current work identified the promoter of the human SEPT12 gene and provided key evidence about its transcriptional regulation via E2 and 5α-DHT. Since SEPT12 has an important role in spermatogenesis, SEPT12 expression analysis can be developed as a potential tool for the assessment of environmental or food pollution by hormones or for the evaluation of the risk of endocrine-disrupting chemicals (EDCs) in general.

The Effects of Phytosterols Extracted from Diascorea alata on the Antioxidant Activity, Plasma Lipids, and Hematological Profiles in Taiwanese Menopausal Women.

The efficacy of phytosterols extracted from Diascorea alata on antioxidant activities, plasma lipids and hematological profiles was assessed in postmenopausal women. Gas chromatography and mass spectrophotometry was employed to determine the steroid content of Taiwanese yam (Diascorea alata cv. Tainung No. 2). A two-center, randomized, double-blind, placebo-controlled clinical investigation on 50 postmenopausal women randomly assigned to two groups treated for 12 months with placebo or two sachets daily of Diascorea extracts containing 12 mg/dose was carried out. The main outcome measures were the plasma antioxidant activities, hematological profiles, and the concentrations of plasma lipids, including cholesterol, triglyceride, low density lipoprotein, high density lipoprotein, very low density lipoprotein,, and apolipoprotein A1 and B. A one-way analysis of covariance (ANCOVA) test was performed to investigate the significance. Beta-sitosterol, stigmasterol, 22-23-dihydro-, and γ-sitosterol were major phytosterols determined from Diascorea extracts. At six months in those receiving Diascorea, there were significantly decreased leukocyte counts (p < 0.01) and improvement on antioxidant activity of malondialdehyde (p < 0.001). After 12 months' treatment, elevations of hematocrit and mean corpuscular volume (p < 0.01) were noted in those receiving Diascorea. Moreover, the low dose Diascorea consumption in menopausal women for one year generally did not present positive effects on lipid profiles.

Changes in PPARδ expression in a rat model of stress-induced depression.

Depression is a common mental disorder that has been linked to a decrease in the expression of serotonin and/or the serotonin transporter in the brain. Antidepressants that target the monoaminergic system are widely used in the clinical setting. Peroxisome proliferator-activated receptor δ (PPAR δ) overexpression or activation is thought to improve depression-like behaviours in rodents. The present study was designed to characterize the changes in PPARδ expression in the hippocampus in rats with stress-induced depression. We used an unpredictable chronic mild stress (CMS) model in rats to study the role of PPARδ in the hippocampus. Behaviour was evaluated via a forced swim test (FST), a tail suspension test (TST), and a sucrose preference test (SPT). Then, the changes in PPARδ expression and other signals were determined using Western blots. We found that PPARδ expression in the hippocampus was markedly reduced in rats with depression. Moreover, the expression of the serotonin transporter was also significantly decreased. Treatment with a PPARδ agonist enhanced the expression of PPARδ and the serotonin transporter in the hippocampus of rats with stress-induced depression. Additionally, treatment with a PPARδ agonist increased the expression of the serotonin transporter in cultured hippocampal (H19-7) cells, and this action was ablated in the absence of PPARδ, which was attenuated with shRNA. Taken together, we found that PPARδ plays an important role in the regulation of serotonin transporter expression and that chronic stress may lower PPARδ expression in the brain via apoptosis and may attenuate serotonin transporter expression, thus inducing depression in rats.

Screening of a panel of steroid-related genes showed polymorphisms of aromatase genes confer susceptibility to advanced stage endometriosis in the Taiwanese Han population.

OBJECTIVE: To establish a multilocus model for studying the effect of steroid-related genes on advanced stage endometriosis. MATERIALS AND METHODS: A total of 121 patients with advanced stage endometriosis and 171 control women were included. Eighteen single-nucleotide polymorphisms (SNPs) from nine genes (HSD17B1, HSD17B2, HSD17B5, HSD17B6, CYP17, CYP19, ERα, ERß, and PGR) were genotyped using the TaqMan assays. Logistic regression models were used to evaluate the genetic effects, with adjustment for other covariates. RESULTS: Only the presence of the mutant CYP19 (aromatase gene) was associated with a significantly increased risk of endometriosis after adjusting for age, BMI, and parity (p = 0.002, OR = 2.69; 95% CI = 1.44-5.02). No association was ascertained between the other investigated SNPs and endometriosis. CONCLUSION: Polymorphisms of the aromatase gene confer susceptibility to advanced stage endometriosis in the Taiwanese Han population.

SEPTIN12 genetic variants confer susceptibility to teratozoospermia.

It is estimated that 10-15% of couples are infertile and male factors account for about half of these cases. With the advent of intracytoplasmic sperm injection (ICSI), many infertile men have been able to father offspring. However, teratozoospermia still remains a big challenge to tackle. Septins belong to a family of cytoskeletal proteins with GTPase activity and are involved in various biological processes e.g. morphogenesis, compartmentalization, apoptosis and cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men, is exclusively expressed in the post meiotic male germ cells. Septin12(+/+)/Septin12(+/-) chimeric mice have multiple reproductive defects including the presence of immature sperm in the semen, and sperm with bent neck (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a potential sterile gene in humans. In this study, we sequenced the entire coding region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and identified ten variants. Among them is the c.474 G>A variant within exon 5 that encodes part of the GTP binding domain. The variant creates a novel splice donor site that causes skipping of a portion of exon 5, resulting in a truncated protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for the c.474 A allele had teratozoospermia (abnormal sperm <14%) and their sperm showed bent tail and de-condensed nucleus with significant DNA damage. Ex vivo experiment showed truncated SEPT12 inhibits filament formation in a dose-dependent manner. This study provides the first causal link between SEPTIN12 genetic variant and male infertility with distinctive sperm pathology. Our finding also suggests vital roles of SEPT12 in sperm nuclear integrity and tail development.

SEPT12 mutations cause male infertility with defective sperm annulus.

Septins are members of the GTPase superfamily, which has been implicated in diverse cellular functions including cytokinesis and morphogenesis. Septin 12 (SEPT12) is a testis-specific gene critical for the terminal differentiation of male germ cells. We report the identification of two missense SEPT12 mutations, c.266C>T/p.Thr89Met and c.589G>A/p.Asp197Asn, in infertile men. Both mutations are located inside the GTPase domain and may alter the protein structure as suggested by in silico modeling. The p.Thr89Met mutation significantly reduced guanosine-5'-triphosphate (GTP) hydrolytic activity, and the p.Asp197Asn mutation (SEPT12(D197N)) interfered with GTP binding. Both mutant SEPT12 proteins restricted the filament formation of the wild-type SEPT12 in a dose-dependent manner. The patient carrying SEPT12(D197N) presented with oligoasthenozoospermia, whereas the SEPT12(T89M) patient had asthenoteratozoospermia. The characteristic sperm pathology of the SEPT12(D197N) patient included defective annulus with bent tail and loss of SEPT12 from the annulus of abnormal sperm. Our finding suggests loss-of-function mutations in SEPT12 disrupted sperm structural integrity by perturbing septin filament formation.

Polymorphisms of dioxin receptor complex components and detoxification-related genes jointly confer susceptibility to advanced-stage endometriosis in the taiwanese han population.

PROBLEM: To establish a multilocus model for studying the effect of dioxin receptor complex components and detoxification-related enzymes on advanced endometriosis. METHOD OF STUDY: Six single-nucleotide polymorphisms (SNPs) and two deletion polymorphisms from eight genes (CYP1A1, CYP1B1, GSTM1, GSTT1, GSTP1, AhR, ARNT, and AhRR) were genotyped. RESULTS: In the single SNP analysis, GSTM1 null type and AhRR variant type were associated with a significantly increased risk of endometriosis [odds ratio (OR)=2.38 and 2.45, respectively]. Using multiple SNPs in the logistic regression for covariates, wild-type AhR and mutant AhRR combination was significantly higher in patients (67.8%) than in controls (48.0%) (OR=2.76). On the other hand, mutant AhRR in combination with GSTM1 null genotype was significantly higher in patients (35.5%) than in controls (19.3%) (OR=6.12). CONCLUSION: Polymorphisms of dioxin receptor complex components and detoxification-related genes jointly confer susceptibility to advanced-stage endometriosis in the Taiwanese Han population.

Protein tyrosine phosphatase non-receptor type 14 is a novel sperm-motility biomarker.

PURPOSE: To understand the molecular basis of sperm-motility and to identify related novel motility biomarkers. METHODS: Two-dimensional electrophoresis (2DE) followed by Reverse-phase-nano-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (RP-nano-HPLC-ESI-MS/MS) were applied to establish the human sperm proteome. Then the sperm proteome of moderate-motile human sperm fraction and that of good-motile human sperm fraction from pooled spermatozoa of forty normozoospermic donors (Group 1 subjects) were compared to identify the dysregulated proteins. Among these down-regulated proteins, Protein tyrosine phosphatase non-receptor type 14 (PTPN14) was chosen to reconfirm by Western blotting and semi-quantitative reverse transcription polymerase chain reaction. For clinical application, Western blotting and real-time reverse transcription polymerase chain reaction was performed to compare the expression level of PTPN14 in (Group 2 subjects) nine normozoospermic controls and thirty-three asthenozoospermic patients (including 21 mild asthenozoospermic cases and 12 severe cases). Finally, bioinformatic tools prediction and immunofluorescence assay were performed to elucidate the potential localization of PTPN14. RESULTS: The expression levels of three proteins were observed to be lower in the moderate-motile sperm fraction than in good-motile sperm of group 1 subjects. Among three proteins with persistent down-regulation in the moderate-motile sperm, we reconfirmed that the expression level of PTPN14 was significantly lower in both mRNA and protein levels from the moderate-motile sperm fraction. Further, down-regulation of PTPN14 was found at the translational and transcriptional level in the asthenozoospermic men. Finally, Bioinformatic tools prediction and immunofluorescence assay showed that PTPN14 maybe predominantly localized at the mitochondria in the midpiece of human ejaculated sperm. CONCLUSIONS: Proteomics tools were applied to identify three possible sperm motility-related proteins. Among these proteins, PTPN14 was highly likely a novel sperm-motility biomarker and a potential mitochondrial protein.

In vitro fertilization: four decades of reflections and promises.

BACKGROUND: In 2010, Robert Edwards was awarded the Nobel Prize in Medicine for his pioneering work in the development of in vitro fertilization, a field that has touched millions of lives across the globe. Edwards dedicated his career to helping couples overcome infertility. He first established principles of early embryo development that served as the foundation for his later work. In the 1960s, he achieved the first human fertilized oocyte in vitro while at the Johns Hopkins Hospital. He then continued his work at Cambridge University. In 1978, the world witnessed the birth of the first "test tube baby". This achievement is a landmark not only in the reproductive sciences but also in the history of mankind's technological evolution. SCOPE OF REVIEW: This article outlines the development and progression of IVF from its infancy to the refined and broadly utilized technology offered to patients today. We describe the evolution of the field and the current state of IVF, including its current technological and social challenges. MAJOR CONCLUSIONS: We congratulate Professor Edwards for his well-deserved recognition as Nobel Laureate in Medicine. GENERAL SIGNIFICANCE: This article is a tribute to Edwards for his exceptional accomplishments in this specific and rewarding field of modern medicine.

Quantitative trait analysis suggests polymorphisms of estrogen-related genes regulate human sperm concentrations and motility.

BACKGROUND: Human spermatogenesis is regulated by complex networks, and estrogens are recognized as one of the significant regulators of spermatogenesis. We tested the associations between variants of estrogen-related genes and semen parameters. METHODS: We performed genotyping for genetic variants of estrogen-related genes and quantitative trait analysis of fertile and infertile men with well-characterized reproductive phenotypes. Men with known semen parameters (n= 677) were enrolled, including 210 fertile men and 467 infertile men. A total of 17 genetic markers from 10 genes, including 2 estrogen receptors (ER-α, ER-ß), 7 estrogen synthesizing/metabolizing genes (CYP19A1, HSD17B1, CYP1A1, CYP1B1, COMT, GSTM1, GSTT1) and 1 transport gene (SHBG) were genotyped. Sperm concentration, motility and morphology were taken as quantitative traits to correlate with genetic variants in the estrogen-related genes. RESULTS: Five genes (rs1801132 and rs2228480 of the ER-α gene, rs1256049 and rs4986938 of the ER-ß gene, rs605059 of the HSD17B1 gene, rs1799941 of the SHBG gene and rs1048943 and rs4646903 of the CYP1A1 gene) were found to be significantly associated with sperm concentration (P< 0.01), while five genes (rs1801132 of the ER-a gene, rs1256049 of the ER-ß gene, rs1048943 of the CYP1A1 gene, rs605059 of the HSD17B1 gene and rs1799941 along with rs6259 of the SHBG gene) were associated with sperm motility (P< 0.01). None of the estrogen-related genes were associated with sperm morphology. With an increasing number of risk alleles, sperm concentration and motility tended to deteriorate and show a loci-dosage effect. CONCLUSIONS: Quantitative trait analysis based on a limited number of genetic markers suggests that estrogen-related genes mainly regulate sperm concentration and motility.

Abdominal mesotherapy injection extended the absorption of follicle-stimulating hormone.

Abdominal mesotherapy injection of recombinant human FSH (rhFSH) was well tolerated with increased net absorption (AUC0-∞ 4,655.3 IU·h/L and t1/2 247.6 h) up to 360 hours compared with those of 120 hours (AUC0-∞ 1,915.7 IU·h/L and t1/2 101.8 h). The extended absorption of rhFSH suggests that abdominal mesotherapy injection mode be considered for future administration of rhFSH in controlled ovarian hyperstimulation.