Involvement of blood mononuclear cells in the infertility,age-associated diseases and cancer treatment

Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system(TCS), where they exhibit morphostatic function by stimulatingproliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system(IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage Ⅳ ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.     

A cytogenetic study of Kuwaiti couples with infertility and reproductive disorders: short arm deletion of chromosome 21 is associated with male infertility

Chromosomal anomalies may be a reason for both male and female infertility. The aim of this study was to investigate the contribution of chromosomal abnormalities in sterile couples from Kuwait. A total of 118 patients with clinical diagnosis of infertility was analyzed using cytogenetic banding techniques. Common chromosomal abnormalities were detected in 12 patients. We describe here one new case of an infertile male with the karyotype 46,XY, del(21)(pter;q11.2). The overall incidence of 11% abnormality indicates that routine chromosome analysis of infertile couples in Kuwait should be considered before the planning of intracytoplasmic sperm injection.     

Mitochondrial dysfunction in reproduction

The mitochondrial genome passes from one generation to the next by way of the egg's cytoplasm, so ordinarily an individual's mitochondrial DNA (mtDNA) is entirely derived from his or her mother. A potential mother has a finite number of eggs, or oocytes, all of which were formed when she herself was still a fetus, many years before she can conceive. The eggs are progressively depleted through childhood and her reproductive years at a much faster rate than is accounted for by ovulation. Up to a decade before the ultimate depletion of ovarian follicles (and hence oocytes) at or soon after menopause, cytoplasmic senility of the remaining eggs leads to physiological sterility; a phenomenon that is suspected of being mitochondrially based and has been termed the oopause. When ovulation and conception occur, oxidative phosphorylation and other mitochondrial functions of the fertilized oocyte are thought to be essential to the early embryo well before it implants in the uterus. The competition between follicles to deliver the oocyte that will be fertilized and which will found a new generation could also be mitochondrially based, but the mechanism remains to be elucidated. Increasing experience with the culture of human embryos in vitro is highlighting the importance of mitochondrial metabolism generally, and the avoidance of excessive generation of reactive oxygen species in particular. Paradoxes abound in the experimental data, however. Although natural selection operates on mitochondria only in females (and in extreme cases through the survival of their offspring), reproductive disturbance from mitochondrial mutations is most obvious in males, who typically have reduced sperm motility. mtDNA point mutations such as T8993G, which is serious enough to cause the death of infants from Leigh disease in the first few years of life, can carry through the female germ line apparently unhindered; yet mtDNA deletions that cause a less severe phenotype, and which typically manifest at a later age, are effectively blocked from transmission to offspring--a phenomenon in accord with early experimental observations that deleted mtDNA species are less common in cleaving embryos than in unselected preovulatory oocytes. A mitochondrial basis for ooplasmic aging has not been convincingly established, but the novel IVF-based practice of micro-aspiration and transfer of ooplasm from younger eggs to older eggs, which includes the transfer of mitochondria, appears in preliminary studies to have some clinical efficacy in rejuvenating fertility in older women.     

促排卵药物与卵巢癌关系的研究进展

随着人们生活环境和生活方式的改变,目前不孕症的发病率逐年增高,体外受精-胚胎移植技术IVF的发展有效解决了女性不孕问题,然而这一技术所采用的高剂量促排卵药物所引起的体内激素水平的改变以及短时间内大量排卵导致卵巢表面上皮的反复损伤与修复是否与后期卵巢癌的发生有关联?针对这一问题,国内外学者曾对此进行了一系列机制研究及大量的流行病学调查,但是已完成的研究中仍存在随访时间较短、采用IVF治疗的女性平均年龄较低等问题,使得促排卵药物使用与卵巢癌的关系仍没有确切定论。本文对国内外促排卵药物与卵巢癌关系的研究进展进行了综述。     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

摘要目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60 例我院收治的采用宫腔镜联 合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60 例不孕 症患者中,56.7 %的患者患有慢性盆腔炎,16.7 %的患者为子宫内膜异位症,11.7 %的患者为多囊卵巢综合征;单纯腹腔镜检查的 阳性检出率为60.0 %,单纯宫腔镜检查的阳性检出率为28.3 %,宫腔镜联合腹腔镜检查的阳性检出率高达91.7 %,宫腔镜联合腹 腔镜镜检阳性发现率明显高于前二者(P < 0.05)。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38.3 %、48.3 %和 13.3 %,经宫腔镜联合腹腔镜治疗后分别为11.7 %、50.0 %和38.3 %,差异均有统计学意义(P<0.05)。34 例原发性不孕患者,术后 13例妊娠,妊娠率38.2 %;26 例继发性不孕患者,术后15 例妊娠,妊娠率57.7 %;总妊娠率为46.7 %,其中宫外孕2例。结论：宫 腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准 确率及治愈率。     

AZF microdeletions on the Y chromosome of infertile men from Turkey

Intervals V and VI of Yq11.23 regions contain responsible genes for spermatogenesis, and are named as "azoospermia factor locus" (AZF). Deletions in these genes are thought to be pathogenetically involved in some cases of male infertility associated with azoospermia or oligozoospermia. The aim of this study was to establish the prevalence of microdeletions on the Y chromosome in infertile Turkish males with azoospermia or oligozoospermia. We applied multiplex polymerase chain reaction (PCR) using several sequence-tagged site (STS) primer sets, in order to determine Y chromosome microdeletions. In this study, 61 infertile males were enrolled for the molecular AZF screening program. In this cohort, one infertile male had 46,XX karyotype and the remaining had 46,XY karyotypes. Forty-eight patients had a diagnosis of azoospermia and 13 had oligozoospermia. Microdeletions in AZFa, AZFb and AZFc (DAZ gene) regions were detected in two of the 60 (3.3%) idiopathic infertile males with normal karyotypes and a SRY translocation was determined on 46,XX male. Our findings suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.     

补脾滋肾汤联合针灸治疗多囊卵巢综合征不孕症的临床疗效观察

摘要 目的：观察补脾滋肾汤联合针灸治疗多囊卵巢综合征（PCOS）不孕症的临床疗效。方法：选择2018年9月~2020年9月就诊的120例PCOS不孕症患者,随机分为观察组和对照组各60例。均给予口服枸橼酸氯米芬基础治疗,观察组在基础治疗上增加补脾滋肾汤联合针灸治疗,28 d为一个治疗周期,对比两组患者3个疗程后总有效率、中医证候量表评分、BMI（体质量指数）、月经情况、排卵情况、妊娠情况、血清性激素指标[T（睾酮）、LH（促黄体生成激素）、FSH（促卵泡生成激素）]、B超测定子宫内膜容受性指标[子宫内膜厚度、PI（子宫内膜螺旋动脉搏动指数）与RI（阻力指数）]。结果：治疗3个疗程后观察组的临床总有效率为90%（54/60）,高于对照组的83%（50/60）（P<0.05）。经过3个疗程治疗后,两组PCOS不孕症患者中医症候量表评分改善,月经情况改善,两组排卵率、妊娠率提高,且观察组高于对照组（P<0.05）。治疗3个疗程后,两组BMI、RI、PI、LH、T均下降,且观察组低于对照组（P<0.05）;两组子宫内膜厚度、FSH均增高,且观察组高于对照组（P<0.05）。结论：补脾滋肾汤联合针灸治疗多囊卵巢综合征不孕患者通过中药滋补脾肾、针灸治疗后,有效缓解了临床症状,性激素水平得到调节、体重减轻,提高调经促排卵助孕率,疗效确切。     

Infertility,abortion, and biotechnology

Patterns of reproductive failure described in humans and other mammals suggest that reproductive failure may in many instances be the result of adaptations evolved to suppress reproduction under temporarily harsh conditions. By suppressing reproduction under such conditions, females are able to conserve their time and energy for reproductive opportunities in which reproduction is most likely to succeed. Such adaptations have been particularly important for female mammals, given (a) the amount of time and energy that reproduction requires, and (b) the degree to which reproductive conditions can vary. The existence of conscious and unconscious mechanisms to suppress reproduction under poor conditions has several implications for obstetric/gynecologic practices. Two implications are discussed with reference to biotechnological advancements in our ability to facilitate conceptions and manage problem pregnancies: (a) potential dangers of sophisticated technologies overriding natural fertility controls; and (b) the need for greater appreciation of the association between psychosocial stress and reproductive failure in the treatment of reproductive problems. Implications for elective abortion practices are discussed as well. The ideas for this paper were developed while the author was a recipient of a Career Development Award from the Harry Frank Guggenheim Foundation. Dr. Wasser received a B.S. degree of Zoology from Michigan State University in 1975, a Masters of Science in Zoology from the University of Wisconsin-Milwaukee in 1976, and a Ph.D. in Psychology from the University of Washington in 1981. He is co-director of the Animal Behavior Research Unit, a long-term study on the behavioral ecology and reproduction of free-ranging yellow baboons at Mikumi National Park, Tanzania. Dr. Wasser’s primary research focus is on the evolution of reproductive strategies in female mammals. His work includes research on human infertility and abortion. He is also working on the breeding of endangered species in captivity under a Research Development Award from the National Zoological Park of the Smithsonian Institution.     

Roles of kisspeptin in IVF/ICSI-treated infertile women and in human granulosa cells

Kisspeptin, a crucial central regulator of reproduction, has been used as a trigger in in vitro fertilization (IVF) treatment. This study aimed to investigate the roles of kisspeptin in IVF treatment in infertile females (n = 30); and in steroidogenesis in human granulosa-like tumor cell line (KGN). In the human study, blood was collected at three time points including (1) the beginning of gonadotropin stimulation (Phase I), (2) around eight days after gonadotropin stimulation (Phase II), and (3) on the day of ovum pick-up (Phase III). Follicular fluid (FF) was collected at Phase III. Serum human chorionic gonadotropin (hCG) was measured 15 days after embryo transfer and fetal heart beats were determined around 42 days of menstrual cycle to classify the subjects into successful and unsuccessful groups. FF kisspeptin levels were higher in successful compared with unsuccessful subjects (P < 0.01). Kisspeptin levels were significantly higher in FF than in serum in successful subjects (P < 0.05) but were comparable in unsuccessful subjects. Serum kisspeptin was comparable among three phases in the successful group but its levels in Phase III were significantly lower compared with Phase I in the unsuccessful group (P < 0.01). Serum kisspeptin in Phase II/III had positive correlations with serum E2 in Phases II and III and the outcomes of IVF/intracytoplasmic sperm injection (ICSI) treatment including serum hCG levels. For the cell experiment (n = 3), kisspeptin treatment in the presence of FSH together with IGF-1 enhanced CYP19A1 (aromatase) mRNA expression compared with control. FSH alone increased aromatase concentrations in the supernatant compared with control and kisspeptin at the dose of 10^-2 mmol/L with FSH enhanced aromatase concentrations in the supernatant compared with FSH alone (P < 0.001 all). In conclusion, kisspeptin enhanced aromatase expression and secretion and was associated with positive outcomes of IVF/ICSI treatment. Further studies regarding supplementation of kisspeptin could reveal its beneficial effects on IVF/ICSI treatment.