Pregnancy Guide

The Pregnancy Miracle System

The author of the Pregnancy Miracle book Lisa Olson, has spent an inordinate amount of time involved in Chinese medicine research and is a successful health consultant, alternative health and nutrition specialist, as well as former infertility sufferer herself. The author explains that acupuncture has been used for centuries in China to exchange electrons with the body's meridians, or lines of energy running throughout the body. These lines of energy are, biologically speaking, the folds between cells that occur as we grow. The author goes into much more detail, discussing the various meridians and how they affect fertility. Pregnancy Miracle is appropriate if you want to get pregnant in the next few months. But, Ill warn you that it takes time to get pregnant, even if you follow the steps outlined in the book. If you are not patient enough to follow through, then this book may not be right for you. More here...

Pregnancy Miracle Summary

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Author: Lisa Olson
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Highly Recommended

The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this manual are precise.

When compared to other e-books and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

Pilot efficacy study in IVF

In an open, pilot efficacy study the effects of recombinant FSH in assisted reproduction were investigated. The approach used various down-regulation protocols to assess whether the administration of an FSH-only preparation in these circumstances would be sufficient for follicular development and adequate steroidogenesis. In total, 51 infertile women were treated with recombinant FSH alone (group I), or with recombinant FSH in conjunction with buserelin intranasal spray 4 x 150 ag daily in a short protocol (group II) or in a long protocol (group DI), or using triptorelin in a long protocol, giving a single dose of 3.75 mg intramuscularly (group IV) or daily subcutaneous injection of 200 fig (group V). The pivotal trial in the program encompassed 1000 cycles. This study was set up in order to detect even small differences between both groups. The primary endpoints, as defined prior to starting the study, were the number of oocytes retrieved and the ongoing pregnancy rate, defined as...

SMAR Aberrations and Disease

Changes in nuclear matrix attachment by either the loss of association or by binding to a previously cryptic site have been implicated in the onset of several genetic diseases and disorders. In case of male infertility, the loss of a S MAR was found to arrest expression (Kramer et al. 1997). On the other hand, interactions between originally domesticated elements may trigger genomic instability such as for various forms of cancer where sites of chromosomal fragmentation localize to S MARs (review Bode et al. 2000). Although some of the mechanisms remain unknown, S MARs continue to reveal a multitude of varied roles in pathogenesis that reflect aspects of their complex nature (Linnemann et al. 2007 review Galande 2002).

Outlook and Perspectives

The term epigenetics was introduced in the 1940s by the British embryologist and geneticist Conrad Waddington as the interactions of genes with their environment, which bring the phenotype into being. Nowadays, the term refers to multiple modifications that influence gene activity without altering the DNA sequence. In the past, research has focused on transcription factors and signal transduction pathways associated with turning genes on and off. Only in the last decade scientists have touched the next layer in the flow of information, the more so as there was awareness of an epigenetic code that is central to processes such as development, aging, cancer, mental health and infertility. Since epigenetic changes are much easier to reverse than mutations, drugs that remove or add the chemical tags are at the forefront of cancer therapy.

Menstrual Irregularities and Bipolar Disorder

PCOS is one of the most common endocrine disorders occurring in reproductive-aged endocrine disorder with an estimated prevalence of between 4 and 6 38 . It is characterized by chronic anovulation and hyperandrogenism 39 . Chronic ano-vulation can lead to menstrual abnormalities and infertility. Hyperandrogenism can manifest as hirsutism (excess hair growth on the face), acne, and male-pattern balding. Metabolic consequences of PCOS include obesity and IR, which may lead to type-2 diabetes mellitus and cardiovascular disease (CVD) 39-42 , and underscores the relationship between reproductive abnormalities and IR in women. PCOS is associated with overweight or obesity in approximately 50 of women with the disorder 43 . Even if they are normal weight, individuals with PCOS tend to have a higher proportion of abdominal body fat 44, 45 , which is a risk factor for both IR 46 and CVD 47 . Lipid abnormalities have also been found at high rates among women with PCOS, including low...

Choosing the Experimental Animal

Since NSC therapy has yet to be approved for human clinical trials, experimental animals must be used. Mice are generally used for several reasons. First, as mammals, they share many homologous features with humans which will be very important in years to come when these studies are translated into clinical trials. Since the murine genome has already been sequenced, one can easily correlate the murine genes and their human homologs. Additionally, we now have engineered many murine lines expressing specific models of human disease or CNS insult such as lesions, tumors, parkinsonism and global demyelination (as observed in multiple sclerosis and many congenital metabolic disorders). Logistically, mice are small, inexpensive and easily maintained. They have quick gestations and high pregnancy rates resulting in higher and more quicker yields than in other animal models. Lastly, mice can be exploited in a manner often considered unethical in humans and more highly developed animals.

Controlled ovarian hyperstimulation

In order to reliably assess the safety and efficacy of Organon's recombinant FSH, a large-scale clinical trial program in IVF was organised. This included studies which were all prospective and randomised. Most of them were multicentre. Comparative drugs involved hMG and urinary FSH, and various GnRH-agonists were applied.

Chamaelirium luteum L A Gray

False unicorn is one of the primary botanicals used in Western herbal medicine for its putative ability to promote female fertility and as a uterine tonic. It is reported by some to be relatively scarce and has been known to be subject to adulteration with a different species of plant known as aletris (aka true unicorn or stargrass, Aletris farinosa). Aletris is much less expensive and different in its action than false unicorn. The two species are readily distinguished from one another and care should be taken to differentiate between them (see Aletris).

Ovulation in clomiphene resistant normogonadotropic anovulatory women

The cumulative ovulation rates did not differ significantly between both treatment groups and were 95 and 96 for recombinant FSH and urinary FSH, respectively. Taking all cycles together, 155 out of 223 recombinant FSH cycles were ovulatory (69.5 ) compared to 92 out of 138 urinary FSH cycles (66.7 ). Cumulative pregnancy rates were 27 in the recombinant FSH group, compared to 24 in the urinary FSH group. The miscarriage rates were 31 and 32 , respectively, in the recombinant FSH and urinary FSH groups. The higher efficiency of recombinant FSH was demonstrated by a significantly shorter treatment duration to reach ovulation a median of 10 days (range 4-27) compared to 13 days (range 4-49) after urinary FSH treatment (p

Discussion of findings in the development

A number of reasons can be hypothesised as cause for the increased pregnancy rate in IW after recombinant FSH treatment. First, the higher pregnancy rates directly following the fresh transfer suggests a higher embryo quality after recombinant FSH treatment. This may be related to an increased number of available embryos enabling the embryologist to replace the morphologically best embryos. It is believed that embryo morphology correlates well with the chance for implantation and therefore pregnancy. However, one can not exclude the possibility that oocyte quality and therefore embryo quality are influenced by the type of gonadotropin preparation used. It has been shown in in vitro experiments with mammalian oocytes that meiotic progression, polar body emission, cumulus-oocyte interactions, and oocyte cytoskeletal organisation are influenced by the presence or absence of gonadotropins in the culture medium. One can speculate that the different nature of follitropin beta compared to...

C 17aEthynylestradiol

This is a classic example of a drug-drug interaction and one of the few attributed to induction, instead of inhibition. In the early 1970s several German reports indicated that women who were using oral contraceptives began spotting or became pregnant after using rifampicin or barbiturates (Reimers and Jezek, 1971 Nocke-Finck et al, 1973 Janz and Schmidt, 1974). The major estrogen in oral contraceptives is 17a-ethynylestradiol (Fig. 4), which is metabolized via 2-hydroxylation, plus other pathways (Bolt et al., 1973 Guengerich, 1990b). Administration of rifampicin resulted in the faster elimination of 17a-ethynylestradiol in volunteers (Bolt et al., 1977).

Female Reproductive Problems in Fish

Xenobiotic induced disruption of female fertility follows essentially the same pattern as that of the male and can be caused by changes in pituitary-hypothalamic function, primary disruption of ovarian structure or hormone secretion, or changes in the rate of hormone deactivation. In addition, there may be changes in the synthesis of estrogen induced production of the yolk protein by the liver (vitellogenesis), which in turn can lead to failure to lay down sufficient yolk in the developing oocytes. Vitellogenesis provides a valuable biomarker for endocrine dysfunction in both sexes 6 but is more properly considered as part of the liver function.

Ovarian Structure and Hormones

The main factor causing the increase in ovarian weight during the reproductive development of fish is the deposition of yolk into the developing eggs. Abnormal development of the ovary, like the testis, can be caused by lack of stimulation by pituitary hormones, failure of steroid synthesis or direct cellular damage. The most commonly observed effect in the ovary is a decrease in the numbers of large yolky eggs together with increased numbers of immature oocytes, suggesting a primary effect on pituitary function. Such changes have been observed with heavy metals (arsenic, cadmium, lead, mercury), organochlorine (DDT, endosulfan, aldrin, chlordecone, y-BHC, methoxychlor), organophosphate (monocrotophos, fenthion, cythion, fenitrothion, phenthoate, malathion, chlorfenvinphos, tetrach-lorvinphos, mevinphos) and carbamate (carbaryl, carbofuran) pesticides. Among industrial chemicals, effects have been shown predominantly for PCBs and PAHs, and contaminated aquatic ecosystems such as those...

Temporal Trends and Geographic Variability in Adverse Male Endpoints

Studies of local trends in semen quality men from infertility clinics Variability between areas in the rates at which mean sperm density declined was demonstrated in these reanalyses. Heterogeneity is also demonstrated in the many local trend studies that have been published since 1992. Some of these have demonstrated declines in sperm density 39-41 within cities or countries,while others have found no decline or even slight increases in the last 20 years 42 -44 . We have separated those studies conducted on men recruited through infertility clinics (Table 2) and those including candidate semen donors or other men unselected with respect to fertility (Table 3). These data demonstrate considerable temporal and geographic variation in sperm density and other semen parameters. Determining how much of this variation is attributable to environmental

Exposure in the Workplace and from Industrial Accidents

A dramatic example of an occupational exposure to a male reproductive toxicant was reported in 1977. Whorton and Meyer 100 found a history of infertility in male workers strongly linked to the manufacture of the ne-matocide dibromochloropropane (DBCP). This finding was confirmed and exposure-dependent effects on sperm counts, LH and FSH, and impaired sperm motility and morphology documented 100 . Similar findings were reported in DBCP-exposed occupational cohorts in Israel 101 and Hawaii 102 . More recently, a decreased sex ratio has been reported in offspring of exposed workers who recovered sufficient sperm function to conceive 103,104 .

Plausibility of Adverse Effects of EDCs Mechanisms of Gonadal and Accessory Reproductive Organ Differentiation

The initial period of differentiation into a testis or ovary is not dependent on gonadal steroids in either males or females 123,124 . Thus, mammals are unlike fish, amphibians, and reptiles, where gonadal differentiation (primary sex determination) is dependent on environmental factors, such as temperature, that appears to operate through altering gonadal steroid levels in some species 125,126 . This fact makes it plausible that in lower vertebrates environmental EDCs can alter primary sex ratio in a population by directly influencing go-nadal differentiation, and the resultant sex-reversed offspring are all fertile and normal in other respects 126,127 . In contrast, in birds and mammals, high levels of hormones can interfere with normal gonadal differentiation, but sex reversal (for example, development of functional ovaries in genetic males) does not occur. The consequence of endocrine disturbance during gonadal development for birds and mammals is thus infertility and, with...

Developmental Exposure to Diethylstilbestrol DES

Treatment of pregnant females with high doses of DES interferes with the action of Mullerian inhibiting hormone on Mullerian duct regression in male mice 128 and humans 229 . The utricular remnant within the prostate, which is of Mullerian origin, is enlarged and there is marked hyperplasia and metaplasia of prostatic ducts in the central zone of the adult prostate 229,230 . As mentioned above, exposure of the neonatal mouse to high doses of DES has been shown to interfere with normal development of the prostate 213, 231, 232 . Squamous metaplasia of prostatic and coagulating gland (dorsocranial prostate) ductal epithelium in male mice and rats has also been reported after exposure to exogenous estrogen or estrogenic chemicals during early life 128 . This endpoint is also characteristic of the effect of estrogen on rat prostatic cells in culture 200 . Exposure of rats and mice to high doses of DES during development also alters testis development, leading to a decrease in testis size,...

Effects of Perinatal Estrogen Exposure on Fertility and Cancer in Mice

Concerns have been raised regarding the reproductive and health hazards of chemicals in the environment that have potential endocrine disrupting effects. These concerns include increased incidences of breast, ovarian, and uterine cancer, endometriosis, fibroids, infertility, and early menopause in women in men, alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems have been suggested. Studies with the potent synthetic estrogen diethyl-stilbestrol (DES) have shown that exogenous estrogen exposure during critical stages of development results in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES is a potent environmental estrogen, studying its effects at low dose levels in an experimental animal model offers a...

Pregnancy 831 Implantation

The importance of prostaglandins in the implantation process is underlined by the observation that COX inhibitors can delay implantation (reviewed in Psychoyos et al. 75 ). In rodents, there was even an inhibition of implantation after indomethacin administration, which could be overcome by introducing PGE2 into the uterine lumen 84 , However, far too high a dosage of NSAIDs would be needed for therapeutic use as an anti-conception drug in humans. This is underlined by recent studies with mice having a homozygous deletion of the COX-1 gene which had normal pregnancy rates 87 . On the other hand, wild-type blastocysts failed to implant in COX-2 knock out mice 223 ,

FAAH Is an Integrator of Fertility Signals

The above data emphasize a main role for FAAH in the interaction between ECS and sex hormones during male reproduction, and underline its value as promising target to treat infertility problems. This concept can be further extended to other essential fertility signals, like progesterone. This hormone upregulatesfaah gene expression in human lymphocytes by binding to the faah promoter through the Ikaros transcription factor (Maccarrone ei a ., 2003b). Such an effect is synergistic with that ofleptin, the 16-kDa nonglycosylated product of the obese gene that triggers STAT-3 (signal transducer and activator of transcription-3), which in turn binds to a

Prenatal DES Exposure as an Example

For almost 30 years, physicians prescribed DES to women with high-risk pregnancies to prevent miscarriages and other complications of pregnancy. In 1971, a report associated DES with a rare form of reproductive tract cancer termed vaginal adenocarcinoma which was detected in a small number of adolescent daughters of women who had taken the drug while pregnant. Subsequently, DES was also linked to more frequent benign reproductive tract problems in an estimated 90-95 of the DES-exposed daughters reproductive organ dysfunction, abnormal pregnancies, reduction in fertility, immune system disorders, and multiple other effects have been reported. Similarly, DES-ex-posed male offspring demonstrated structural, functional, and cellular abnormalities following prenatal exposure hypospadias, microphallus, retained testes, inflammation, and decreased fertility were reported 10 . DES became one of the first examples of an estrogenic toxicant in humans it was shown to cross the placenta and...

Identifying new receptorsbinding sites by the use of chimeric proteins

Luteinizing hormone releasing hormone (LHRH), also termed gonadotropin-releasing hormone (GnRH) accounts for the hypothalamic-pituitary gonadal control of human reproduction. The involvement of GnRH has been demonstrated in several carcinomas of hormone-responsive tissues. Exploiting this common feature, we constructed a PE-based chimeric toxin (GnRH-PEgg) aimed at targeting those cancer cells bearing GnRH-binding sites.

Programmes of use with MLs

Using strategic control of GI helminths in Aberdeen Angus heifers at autumn-winter time, Steffan et al. (1995) observed, in a group of 156 calves divided into three groups, that ivermectin gave the best results in terms of reduced worm burdens, weight gain and conception rate when compared with oxfendazole-treated or non-treated control groups.

Reproductive cultures containing colloidal silver

Excerpt(s) This application claims priority on U.S. provisional application No. 60 219347, filed on Jun. 14, 2000, the disclosure of which is incorporated by reference herein. A substantial proportion of the swine produced in North America today are produced utilizing artificial insemination. Thus, the ability to preserve animal reproductive samples, such as semen, oocytes and embryos, for use in artificial insemination and other reproductive processes is important. Without this ability, it is not possible to transport animal reproductive samples or store the samples for any length of time thus, the utility of the samples is limited. To protect reproductive samples from bacterial contamination, it has been common practice to introduce antibiotics into the preservation mediums or extender solutions. Although conventional antibiotics can be a low cost and effective way of preserving the samples, there are long term consequences of the continued widespread use of antibiotics. Over time,...

From Protein Subunit Vaccines to Antibody Treatments of Bacterial Infections

Infectious diseases remain a major threat against human life. Microbial infections are still out of control in many parts of the less developed world where they count for most of the deaths, but also cause an often underestimated toll of death (e.g., community acquired Pneumococcal diseases and Pseudomonas infections in patients in intensive care), life-long mutilation (infertility due to Chlamydia trachomatis), medical complication due to nosocomial infections caused most often by Staphylococcus aureus, Enterococcus faecalis, Klebsiella ssp and fungi. It is estimated that nosocomial infections annually add US 5-10 billion to the cost of the national healthcare system in the United States.1 Apart from infections caused by viruses and protozoa that only in specific instances can

GnRHPE chimeric proteins for targeting adenocarcinomas

One such possible candidate gene is GnRH, a decapeptide that is normally synthesized by the hypothalamic neurons and secreted into the hypophysioportal circulation via the portal vessels. It is synthesized as a larger peptide and matures through proteolytic processing and amidation at its C-terminal glycine. Upon reaching the anterior pituitary gland, GnRH selectively stimulates the gonadotroph cells to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thus playing a central role in the neuroendocrine control of human reproduction.

Follicle Stimulating Hormone Receptor Mutations and Gametogenesis

7.2.6.1 FSHR Mutants, Ovarian Dysgenesis, and Infertility The Ala189Val mutation in the FSHR was first identified in a female patient with severely affected gametogenesis (83). The resultant female infertility phenotype was identified in a dominantly inherited pattern of ovarian dysgenesis. Identified in a homozygous form in affecteds, the mutation disrupts the large ECD of the FSHR implicated in ligand binding, while leaving intact the remaining TM-spanning domains and the carboxyl tail (83,84). In vitro studies suggested that the mutation probably affects FSH binding by disrupting the proper protein folding and thereby inactivating the receptor (84,85). Interestingly, although Ala189Val variants have been identified in both sexes, the Asp567Gly variant has only been identified in males. This suggests that this activating FSHR mutation may result in a lethal phenotype in females (83,84). In this context, it is intriguing that there is evidence for an association between homozygosity...

Is there a Common Aetiology

Especially in view of the fact that testicular cancer is more common in individuals with conditions associated with abnormal sexual differentiation during fetal life.27,29,30 Unpublished data by Auger and colleagues also supports a relationship between increasing incidence in testicular cancer and a decline in sperm counts. They have found that in men with testicular cancer there is a 6.2 decrease in sperm counts with each later year of birth (J. Auger and P. Jouannet, personal communication). In addition, cryptorchidism is associated with poor semen quality and higher risk of infertility 1 There appears to be a wide spectrum in the severity of affects on male reproduction, with men with testicular cancer showing a profound decrease in sperm numbers compared with normal men who show a more modest decrease in sperm numbers. Currently, there is no explanation as to why these trends are occurring.

Estrogens And Progestins

Estrogens and progestins are steroid hormones with numerous physiological actions. In women, these include developmental effects, control of ovulation, cyclical preparation of the reproductive tract for fertilization and implantation, and metabolic actions. Estrogens also have important actions in males, including effects on bone, spermatogenesis, and behavior. Estrogens and progestins are used in menopausal hormone therapy (MHT) and contraception in women. Estrogen- and progesterone-receptor antagonists also are available. Antiestrogens are employed in treating hormone-responsive breast cancer and infertility. The main use of antiprogestins has been for medical abortion. Selective estrogen receptor modulators (SERMs) with tissue-selective agonist or antagonist activities are increasingly available.

Selective Estrogen Receptor Modulators And Antiestrogens

Antiestrogens clomiphene and fulvestrant These compounds are pure antagonists in all tissues. Clomiphene (clomid, serophene, others) is approved for the treatment of infertility in anovulatory women fulvestrant (faslodex, ici 182,780) is used to treat breast cancer in women with disease progression after tamoxifen.

Altered Endocrine System Function

Chemicals that disrupt the endocrine system can have profound effects on the development and reproduction of organisms (for examples see Table 1). A classic example is the in utero exposure of young boys and girls to the pharmaceutical estrogen, diethylstilbestrol (DES). The majority of the children born of mothers given DES during pregnancy had measurable alterations of their reproductive organs 40 . Many of the DES daughters exhibit lower fertility or infertility, and sons have elevated occurrence of cryptorchidism and testicular cancer. EDCs, such as DES, have the potential to disrupt the endocrine system by modifying hormone synthesis, control, production, availability, and action. We will briefly document how EDCs can act at each of these levels in the following sections.

Ultrasound Contrast Agents

One approach to prolong the survival of these microcapsules in the circulation and hence extend the period of ultrasound contrast enhancement has been to prevent opsonization by covering the surface of the microparticles with polyethylene gylcol. Clinical applications of these agents are in cardiovascular investigation, tumour imaging and in the determination of fallopian tube patency in patients with infertility. The application of these agents is expected to increase as targeting strategies are employed to direct microcapsules to pathological sites such as tumour or thrombus. It is also envisaged that at high acoustic intensities the ultrasound beam could be used to burst the microcapsule which could be loaded with an appropriate drug, thus increasing local availability of drug at the target site.

Hh And The Gonadotropinreleasing Hormone Receptor

IHH is a disorder characterized by a complete or partial lack of sexual development that may be either congenital or acquired 146, 147 - IHH is a rare disease, with estimated incidence of 1 10,000 to 1 86,000 147 . Patients afflicted with IHH have a deficient pituitary gonadotrope response to gonoadotropin-releasing hormone (GnRH), which results in reduced or apulsatile gonadotro-pin release, delayed onset or absence of puberty, and infertility (for review, see References 4, 146, 147). IHH patients may also present with a variety of anomalies, such as anosmia hyposmia, which is usually diagnosed as Kallmann syndrome, cleft palate, dental agenesis, visual abnormalities, deafness, and mental retardation, among others 146 . The disease may present at birth, adolescence, or adulthood. IHH is genetically heterogeneous, with X-linked recessive, autosomal recessive, autosomal dominant, and apparent sporadic inheritance patterns. Mutations in one of three genes are most commonly associated...

Known Effects of Plant and Fungal Estrogens in Animals and Humans

Although most environmental estrogens are relatively inactive, when compared to steroidal estrogens or DES, the phytoestrogen miroestrol or ethinyl estradiol (EE) are as potent as estradiol in vitro and even more potent than estradiol when administered orally. In addition, many plant estrogens occur in such high concentrations that they induce reproductive alterations in domestic animals 48 . Clover disease , which is characterized by dystocia, prolapse of the uterus and infertility, is observed in sheep grazed on highly estrogenic clover pastures. Permanent infertility (defeminization) can be produced in ewes by much lower amounts of estrogen over a longer time period than are needed to produce clover disease . In domestic animals, feeds contaminated with the zearalenone-producing fungus (Fusarium sp.) induce adverse reproductive effects in a wide variety of domestic animals, including impaired fertility in cows and hyperestrogenism in swine and turkeys 48 .

O Design Of Eicosanoid Drugs

The ability to capitalize successfully on the highly potent biologic effects of the various eicosanoids to develop new therapeutic agents currently seems an unfulfilled promise to medicinal chemists. Although these natural substances are highly potent effectors of various biologic functions, their use as drugs has been hampered by the following factors (a) their chemical complexity and relative instability, which have limited, to some extent, their large-scale production and formulation for clinical testing (b) their susceptibility to rapid degradation in vivo (Fig. 26.3), which limits their effective bioactive half-life and (c) their propensity to affect diverse tissues (particularly the gastrointestinal tract, which may lead to severe nausea and vomiting) if they enter the systemic circulation, even in small amounts. Caution is always recommended with the use of prostaglandin analogs in women of childbearing age because of their potential for inducing dramatic contraction of uterine...

Pregnancy and Lactation

One of the most challenging questions faced by patients and health care practitioners in family planning is whether to initiate or continue antidepressant therapy during conception, pregnancy, and the postpartum period. In exploring the risk-benefit analysis, one needs to consider the potential teratogenic risk of exposure of the antidepressant to the infants against the risks to the unborn children of women with untreated depression during pregnancy. These data are contradicted by several other trials that might be considered more scientifically valid, given their prospective nature. In a cohort study, Kulin et al. (1998) compared rates of major congenital malformations in 237 pregnant women treated with paroxetine, fluvoxamine, or sertraline and found no significant differences among the medication groups compared with control groups. More recently, Hendrick et al. (2003a) followed a total of 138 pregnant females treated with paroxetine, fluoxetine, or sertraline and found that...

Clinical Pharmacology Nitrogen Mustards

The major acute toxic manifestations of mechlorethamine are nausea and vomiting, lacrimation, and myelosuppression. Leukopenia and thrombocytopenia limit the amount of drug that can be given in a single course. Like other alkylating agents, mechlorethamine blocks reproductive function and may produce premature ovarian failure in women and oligospermia in men. Since fetal abnormalities can be induced, this drug should not be used in the first trimester of pregnancy and should only be used with caution in later stages of pregnancy. Breast-feeding must be stopped before therapy with mechlorethamine is initiated.

O Veterinary Uses Of Prostanoids

Since McCracken and coworkers30 demonstrated that PGF2a acts as a hormone in sheep to induce disintegration of the corpus luteum (luteolysis), salts of this prostaglandin and various analogs have been marketed to induce or synchronize estrus in breed animals. This procedure allows artificial insemination of many animals during one insemination period. The following two products are currently available for this purpose.

Miscellaneous Immunosuppressant And Antiinflammatory Agents

Thalidomide is FDA-approved for the treatment of erythema nodosum leprosum. There are reports suggesting its efficacy in actinic prurigo, aphthous stomatitis, Behfet's disease, Kaposi's sarcoma, and the cutaneous manifestations of lupus erythematosus, as well as prurigo nodularis and uremic prurigo. Thalidomide has been associated with increased mortality when used to treat toxic epidermal necrolysis. It also may cause an irreversible neuropathy. Because of its teratogenic effects, thalidomide use is restricted to specially licensed physicians who fully understand the risks. Thalidomide should never be taken by women who are pregnant or who could become pregnant while taking the drug.

The preimplantation embryo and implantation Critical role for the ECS system

Anandamide levels in turn appear to be fine-tuned by varying levels of FAAH. We further know that mRNAFAAH is present in preimplantation and implanting embryos as well as at the implantation site of the uterus (Paria and Dey, 2000 Paria ei a ., 1999), where it inversely correlates with anandamide levels. Maccarrone and colleagues reported FAAH downregu-lation in the uterus of pregnant and pseudopregnant mice during the implantation period (Maccarrone ei a ., 2000a), and in clinical studies this group showed that FAAH concentrations in lymphocytes of women who miscarried were lower than lymphocyte FAAH concentrations from women who gave birth (Maccarrone ei a ., 2000b). In addition, plasma anandamide levels were significantly higher in a subsample of pregnant women with a threatened miscarriage than in those women who gave birth at term (Habayeb ei a ., 2008). Recently, in placental tissue samples from pregnant women, an association was found between the expression of FAAH in the...

Potential Effects of Toxicants on Sex Ratio in Humans and Animals

The effects of exposure to endocrine disruptors during sex differentiation are of special concern for a number of reasons this process is very sensitive to the effects of relatively low doses of endocrine disruptors, the effects are irreversible, i. e., the system is imprinted by the initial hormonal environment, functional alterations of the sex differentiation are often not apparent until after puberty or even later in life, and the abnormalities, which include malformations and infertility, cannot be predicted from the transient alterations in hormone levels produced by similar exposure in adult animals. It is important to understand the key role that animal models play in this research as developmental reproductive tox-icity data are often critical in the assessment of noncancer health effects of EDCs. Furthermore, when similar congenital reproductive abnormalities have been detected in laboratory species, they have dramatically facilitated our understanding of genetic errors of...

Known Effects of Drugs on Human Sexual Differentiation

Diethylstilbestrol (DES) provides an unfortunate example of how in utero exposure to a potent endocrine disruptor with estrogenic activity can alter reproductive development in humans. Although a few cases of masculinized females were noted in the late 1950s, most of the effects of DES were not apparent until after the children attained puberty. Transplacental exposure of the developing fetus to DES causes clear cell adenocarcinoma of the vagina, as well as gross structural abnormalities of the cervix, uterus, and fallopian tube. These women are more likely to have an adverse pregnancy outcome, including spontaneous abortions, ectopic pregnancies, and premature delivery 41 . Some of the pathological effects that develop in males following fetal DES exposure appear to result from an inhibition of androgen action or synthesis (hypospadias, underdevelopment or absence of the vas deferens, epididymis, and seminal vesicles) and anti-Mullerian duct factor (persistence of the Mullerian...

Relevance of an Allosteric mDia1 Inhibitor

Finally, while there is as yet no direct link between mDia activity and the development of disease states, DRFs have been proposed as novel drug targets in cancer due to their role in regulating both the actin and microtubule cytoskeleton (Faix and Grosse 2006) and the importance of these cytoskeletal elements for mitosis and cytokinesis. mDial interacts with the tumor suppressor adenomatous polyposis coli (APC), and may serve as a scaffold for APC-mediated microtubule stabilization (Wen et al. 2004). In addition, mDial binds polycystin 2 (PKD2), a protein linked to the development of polycystic kidney disease (Rundle et al. 2004). Additional evidence for the involvement of these cytoskeletal regulators in the development of disease comes from the human DRFs, where mutations in the genes encoding hDial and hDia2 have been associated with non-syndromic deafness (Lynch et al. l997) and premature ovarian failure (Bione et al. l998). Given the role of DRFs in a number of important...

Effect of HPA Axis on the Reproductive Axis

Stress has long been known to inhibit the reproductive axis, and the work of Christian (1971) demonstrating infertility secondary to high population density is often cited as a seminal report. Shortly after the isolation and sequencing of CRH, it was demonstrated in rats that CRH inhibited LH secretion (Rivier and Vale 1984) and GnRH secretion (Petraglia et al. 1987), and further primate studies showed inhibition of LH secretion by injection of CRH (Olster and Ferin 1987).

Recombinant therapeutic hormones

Female infertility Male infertility Female infertility Female infertility FSH, along with hCG, is utilized medically to treat various reproductive disorders, such as anovulatory infertility. FSH preprations traditionally have been extracted from the urine of post-menopausal women, while hCG is purified from the urine of pregnant women. Urine is hardly an ideal source of any therapeutic agent, rendering attractive production of recombinant forms of gonadotrophins. Gonal F, for example, is a recombinant FSH preparation produced in Chinese Hamster Ovary cells which gained marketing approval in the EU in 1995 and the USA in 1997.

Potential Adverse Effects of Dietary Estrogens

Concern has been expressed that some phytoestrogens may disrupt the developing endocrine system similarly to the effects of other endogenous estrogens 264,265 . Much of this concern has stemmed from animal research. There are well-described examples of phytoestrogen-containing plants inhibiting fertility via estrogenic activity in animals. For instance, sheep grazing on Australian pastures containing a particular type of clover rich in formononetin, which is converted to daidzein in the rumen during fermentation, developed a widespread infertility in the 1940s 248, 266 . Other examples are the moldy corn syndrome in pigs and cattle fed corn contaminated by Fusarium sp., which produces the estrogenic b-resorcyclic acid lactone, zearalenone 267 , and the inhibition of reproduction of California quail by phytoestrogens produced by plants growing in dry conditions 266 . The use of soybean in captive cheetah in Cincinnati zoo was also shown to be responsible for an infertility syndrome,...

Embryonic Stem Cells

Embryonic stem cells (ESCs) are derived from the inner cell mass of blastocyst-stage embryos. Though embryo-derived neural cells have not yet been consistently used for transplantations,28,41,42 they are especially of interest because they are thought to be totipotent, meaning they can give rise to all three embryonic germ layers and therefore theoretically differentiate into all the cell types of the body. ESCs hold great promise for clinical trials however, due to ethical reasons, the source of ESCs is highly regulated and restricted to cell lines from supernumerary embryos (in vitro fertilization) or embryos designated specifically for research.43 46

Conclusion

The earliest clinical studies concerned with androgens measured them mostly by RIA, therefore they suffered from potential cross-reactions. Chromatographic methods coupled with mass spectrometry, namely GC-MS and LC-MS, brought much needed specificity, and the ability to distinguish deuterated, non-radioactive androgens from unlabeled analogs. As a result, stable isotope dilution studies made it possible to give to volunteers small enough doses of labeled T to avoid perturbing endogenous production and yet assess production and clearance rates. The advent of LC-MS-MS brought such higher throughputs than GC-MS and even superior specificity that it is now considered the gold standard. LC-MS-MS measurement of anabolic steroids is a sharper research tool that opens new windows into the understanding of issues of global importance such as human reproduction, contraception, prostate cancer and aging.

Other side effects

NSAIDs given during pregnancy have the potential to cause adverse maternal and fetal effects. Maternal effects include miscarriage, prolongation of pregnancy, and labor, whereas constriction of the ductus arteriosus, renal dysfunction, and hemostatic abnormalities can occur in the fetus and neonate. As weak acids, NSAIDs are excreted in small amounts into human breast milk with little risk for adverse effects in the suckling infant. In a population-based cohort study it was found that the risk of miscarriage was higher if NSAIDs or aspirin were taken around the time of ovulation or conception and for longer than one week. COX-2 inhibitors are classified as pregnancy category C due to increased peri-implantation and post-implantation losses and reduced fetal survival in rats and rabbits. It has been suggested that a delicate balance of the concentration of various types of prosta-noids is essential for maintaining normal blood pressure during pregnancy.12 NSAID use that suppresses the...

Supportive trials

Recombinant FSH compared favourably to hMG with respect to the main efficacy parameters (i.e. number of oocytes retrieved, 11.2 vs 8.3 and ongoing pregnancy rates per attempt and per transfer, 22.2 vs 17.1 and 30.8 vs 22.2 , respectively). However, none of the differences in this study was significant. In this analysis, ongoing pregnancy rates directly following the fresh embryo transfer are significantly higher after recombinant FSH treatment as compared to urinary gonadotropins (22.9 vs 17.9 , p 0.04). When the results of the cryoprogramme were included, this difference was even more significant (26.3 vs 19.9 , p 0.01).

Endocrine Disruption

Fish as Monitors of Endocrine Disruption. Since fish are, perhaps, the class of vertebrate most at risk of endocrine disruption in that their habitat receives the greatest imput of anthropogenic pollution, they might be considered the obvious animal for experimental investigation. Their commercial and dietary importance certainly warrants an investigation of any factors which might lead to a decrease in their populations. In addition, there are some endocrine functions that are far more easily investigated in fish than in mammals. Recent reports in the popular press concentrating on the threat to male fertility posed by environmental estrogens have largely obscured both the fact that female fertility may be equally well compromised and that such effects can be caused by many compounds that are not estrogenic. Although such bias may be attributable to the need to make a good story, or to a male dominated society, they also reflect the fact that males continually produce sperm in...

Safety

The treatment of depression during pregnancy and the postpartum period are discussed in detail in Chapter Diagnosis and Treatment of Depression During Pregnancy and Lactation. Briefly, untreated major depression during pregnancy poses a risk to both mother and fetus. Both psychosocial and pharmacologic treatments have been used to treat pregnant women. When psychotherapeutic interventions are unsuccessful, clinicians and patients are faced with difficult decision regarding the safety of antidepressant therapy. Even the most competent clinician can be overwhelmed by the conflicting safety data generated by many studies. The first practical point is that there are not sufficient data to ensure the safety of any antidepressant. For adverse effects that are as rare as teratogenicity, very large sample sizes are required to avoid a Type II error (not finding an effect that would be evident with larger samples). There are no studies large enough to differentiate the risk of specific...

Special Situations

Recently, a European trial found that elective caesarean section reduced the vertical transmission rate from 10.5 to 1.8 (1999b). However, the mothers in this trial were not treated with potent combination therapy. A consistent, but less striking affect of caesar-ean section on HIV vertical transmission was found in a meta-analysis (1999g). Again, mothers were not necessarily on potent combination therapy at the time of delivery. The Guidelines suggest that pregnant women should be treated in the same manner as nonpregnant women. The teratogenic effect of anti-HIV compounds is not well understood. Consequently, if a woman was not on therapy at the time she became pregnant, a physician should consider holding therapy until after the first trimester. Many anti-HIV compounds have been found to be teratogenic in animal studies (Table VII). Fortunately, major teratogenic effects secondary to anti-HIV drugs have not been seen yet in humans (Culnane et...

Endometriosis

In summary, the relationship between eicosanoids and endometriosis is as follows. Macrophages and lymphocytes are the dominant cells in the peritoneal fluid of endometriotic patients. These cells and endometriotic tissues produce eicosanoids that are responsible for pain and inflammatory reactions and partly responsible for infertility. The cellular changes and their activation in peritoneal fluid, together with the increased prostaglandin and leukotriene concentrations, may also explain the fact that local immunological abnormalities play a crucial role in the etiology or pathophysiology of endometriosis.

Effects on Males

To study the effects of prenatal exposure to DES, outbred CD-1 mice were treated subcutaneously with DES on days 9-16 of gestation, the period of major reproductive tract organogenesis. The doses of DES ranged from 0.01 to 100 g kg during pregnancy, which is equal to or less than doses given therapeutically to pregnant women. In fact, the lower DES doses are comparable to weaker estrogenic compounds found in the environment. Mice were born on day 19 of gestation, and the offspring were followed as they aged. As seen in Table 1, the effects of prenatal exposure to DES on male mice and humans are comparable. Abnormalities such as undescended and hypoplastic testes, infertility, epididymal cysts, sperm abnormalities, hypospadias, microphallus, retained Mullerian duct remnants, prostatic inflammation, and squamous metaplasia of the prostatic ventricle have been reported in both species. The similarity of effects in mice and humans recommends the murine model as a good comparative study....

Effects on Females

Reproductive tract dysfunction Subfertility infertility Structural malformations impairment of female mouse reproductive capacity. Numerous reports of altered pregnancy outcomes and decreased fertility in young women exposed in utero to DES 10 , as well as accidental DES exposure to wildlife resulting in infertility, further point out the importance of these findings in mice, and demonstrate that environmental estrogens play an important role in decreased female fertility. To assess the long-term effects of prenatal DES exposure on the female, mice were sacrificed at 12 to 18 months of age, and reproductive tract tissues were studied for histological alterations. Histological examination revealed lesions throughout the reproductive tracts 28 . The vagina of DES-exposed mice was characterized by excessive keratinization and female hypospadias (urethra opens into the vagina rather than the vulva), and at the highest dose (100 g kg), 25 had epidermoid tumors of the vagina. Vaginal...

Selenium

Selenium deficiency is also found to produce symptoms of hypothyroidism, including goitre, extreme fatigue, mental decline, cretinism, and recurrent miscarriage. It was discovered that selenium was essential to the functioning of the enzyme iodothyronine deiodinases (thyroid hormone deiodinases). Iodothyronine deiodinases are responsible for converting the inactive form of thyroid hormone (thyroxine or T4) to biologically active thyroid hormone (tri-iodothyronine or T3).143 Three different selenium-dependent iodothyronine

Conclusions

A role for the endogenous cannabinoid system in several aspects of human (patho)physiology has been proposed through the activation of cannabinoid and vanilloid receptors, and or via nonreceptor-mediated actions. In the case of AEA, the role of FAAH in controlling its cellular activity seems more critical than that of NAT, NAPE-PLD, or EMT. Here, the activity of FSH, the biological relevance of Sertoli cells, and the main features of the ECS have been briefly described, to put in a better perspective the relevance of FAAH regulation by FSH for male reproduction. In particular, it is suggested that FAAH controls hormone level of AEA, by acting as a molecular integrator of fertility signals. In this context, since low FAAH levels in peripheral lymphocytes (Maccarrone ei a ., 2000), and hence high levels of AEA in blood of pregnant women (Habayeb ei a ., 2008), correlate with pregnancy failure, it can be suggested that FAAH is a critical sensor of reproductive abnormalities also on the...

Future potential

There has been a great deal of concern among clinicians and expectant mothers alike that invasive techniques for fetal diagnosis, e.g. amnio-centesis and chorionic villus sampling, can cause harm to the unborn fetus, e.g. by increasing the risk of miscarriage. However, in 1989 it was shown that it was possible to detect a Y chromosome-specific product from an enriched fetal cell preparation obtained from the peripheral blood of pregnant women carrying a male fetus (Lo et al., 1989). It has been estimated that there are fewer than 10 000 fetal nucleated erythro-cytes present in 20 ml of maternal blood, thus making analysis difficult owing to maternal cell contamination. However, attempts are being made to enrich for fetal cells (using specific antibodies), which would reduce the problems of maternal DNA contamination. If this technique can be optimised in the future, it could easily be used to apply the full range of diagnoses for chromosomal abnormalities associated with birth...

Microfluidics

To date, microfluidics has been successfully implemented in a variety of biological applications of genomics interest including DNA sequencing, PCR amplification, amino acid, peptide, and protein analysis, immunoassays, cell sorting, and in vitro fertilization. In medical diagnostics, microfluidic devices are expected to enhance the prospects of human genotyping in personalized medicine, the efficiency of clinical drug trials, as well as the identification of food-borne pathogens and pathogenic bacteria and viruses. Currently, many companies are exploring the commercial prospects of fully integrated LOC devices that accept a sample, perform a multistep process, and analyze the result.57,175

Fenarimol

Aromatase inhibitors prevent the conversion of androgens to estrogens. This P450 enzyme is highly conserved in a wide variety of tissues and many species, but the overall homology of the gene with other cytochrome P450s is only about 30 . Hence, this enzyme is considered to be in a separate gene family within the overall superfamily. As a consequence of the lack of sequence homology with other P450 enzymes in the steroid pathway, inhibitors of aromatase can display more specific activities than drugs like ketoconazole. In this regard, aro-matase inhibitors have significant clinical uses and often present fewer untoward effects on other endocrine organs. Several fungicides like fenarimol inhibit aromatase activity 196 in mammals, resulting in infertility in both sexes. In our study, fenarimol was administered daily by gavage from weaning, through puberty, mating, gestation and lactation to the P0 generation (at 0,17.5, 35, or 70 mg kg day) while the F1 offspring were only exposed...

Incidence

In the general female population, prevalence is estimated at approximately 10 percent and with infertile women it is 15-25 percent, and 28-74 percent of women undergoing diagnostic laparoscopy for CPP.27,28,29 In the past decade, the incidence has increased, perhaps reflecting delayed childbearing but also the increasing use of laparoscopy and greater awareness of subtle endometriotic lesions.30 Endometriosis may present in any age group (from adolescents to postmenopausal women on hormonal therapy), however most diagnoses are made in women in their thirties or forties.31 Endometriosis has been suggested by

O Hormones

Gonadoliberin, as the name implies, is the gonadotropin-releasing hormone (Gn-RH), also known as luteinizing hormone-releasing hormone (LH-RH). This hypothalamic de-capeptide stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the pituitary. LH-RH is considered to be of potential therapeutic importance in the treatment of hypogonadotropic infertility in both males and females.23

Diagnostic Studies

Diagnostic work-up includes a CBC, ESR, clean catch or catheterized urine for urinalysis and culture, cervical and urethral studies for gonorrhea and chlamydia, pregnancy test (if indicated), wet mount of vaginal secretions, Pap smear if indicated, stool guaiac, and, if diarrhea is present, stool culture. Pelvic ultrasound is warranted but abdominal pelvic computed tomography (CT) scan or pelvic or lower back MRI should only be performed if other pathology is suspected. Other studies (i.e. cysto-scopy, colonoscopy) should be based on patient symptomatology or on consultation with other specialists (urologist, gastroenterologist, neurologist, orthopedist, and physical therapist). Surgical evaluation with diagnostic laparoscopy or hysteroscopy may be considered if initial therapy fails or if pelvic examination is abnormal.

Thalidomide

Thalidomide (thalomid) is best known for the severe birth defects it caused when administered to pregnant women. For this reason, it is available only under a restricted distribution program and can be prescribed only by specially licensed physicians who understand that thalidomide should never be taken by women who are pregnant or who could become pregnant while taking the drug. Nevertheless, it is indicated for the treatment of patients with erythema nodosum leprosum (see Chapter 47) and also is used in conditions such as multiple myeloma. Its mechanism of action is unclear. Rho(D) immune globulin binds Rho antigens, thereby preventing sensitization. Rh-negative women may be sensitized to the foreign Rh antigen on red blood cells via the fetus at the time of birth, miscarriage, ectopic pregnancy, or any transplacental hemorrhage. If the women go on to have a primary immune response, they will make antibodies to Rh antigen that can cross the placenta and damage subsequent fetuses by...

Class A GPCRs

Lastly, inactivating mutations in the FSH receptor (FSHR) have been reported. FSH is important for spermatogenesis in males and is absolutely required for follicle growth in females. Mutations in the FSHR result in ovarian dysgenesis, with amenorrhea and infertility in women. Since the first missense mutation, A189T, in the ECD of the receptor was reported in 1995 207 , eight additional loss-of-function missense mutations have been described. Four of those nine mutants have been characterized as trafficking defective A189T, I160T, and D224V in the ECD and P519T of extracellular loop II 208-211 .

HnRNPs SAFA

Nuclear hormone receptors are paradigms of regulated transcription factor systems that integrate signal transduction into nuclear architecture. The family includes receptors for steroid and thyroid hormones, for vitamin A and vitamin D. These receptors have become important pharmacological targets in a wide variety of clinical disorders, such as fertility issues and autoimmune diseases, which are now amenable to treatment with agonists or antagonists. It is anticipated that blocking the scaffold association of hormone receptors should have comparable effects to such an approach, but on a different level of regulation. Synergistic effects may arise when these treatments are used in combination (review Fackelmayer 2004).

Target animal safety

Were noted and doramectin had no adverse effects on reproductive performance, duration of the oestrous cycle or pregnancy rates. In the segment II III study, synchronized and artificially inseminated heifers were treated subcutaneously with doramectin twice at 600 g kg-1. Each animal received one treatment on a given, randomly assigned day from day 12 to 55 post-insemination (during organogenesis) and all animals received the second treatment at day 224 postinsemination (third trimester). The only clinical sign noted in the study was a few instances of transitory hypersalivation. Data are presented in Table 1.2.4 on the outcome of pregnancy. Doramectin appeared to have no effect on pregnancy. There was no evidence of abortion and no significant differences relative to saline-treated controls in duration of gestation, length of parturition, incidence of dystocia or agalactia, or post-partum health or lactation for heifers treated with doramectin. Viability of neonatal calves (ability...

100 Pregnancy Tips

100 Pregnancy Tips

Prior to planning pregnancy, you should learn more about the things involved in getting pregnant. It involves carrying a baby inside you for nine months, caring for a child for a number of years, and many more. Consider these things, so that you can properly assess if you are ready for pregnancy. Get all these very important tips about pregnancy that you need to know.

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