Infertility

Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term. There are many biological causes of infertility, some which may be bypassed with medical intervention.[1] Women who are fertile experience a natural period of fertility before and during ovulation, and they are naturally infertile during the rest of the menstrual cycle. Fertility awareness methods are used to discern when these changes occur by tracking changes in cervical mucus or basal body temperature Definitions of infertility differ, with demographers tending to define infertility as childlessness in a population of women of reproductive age, while the epidemiological definition is based on "trying for" or "time to" a pregnancy, generally in a population of women exposed to a probability of conception.[2] One definition of infertility that is frequently used by reproductive endocrinologists, the doctors specializing in infertility, to consider a couple eligible for treatment if:

a woman under 35 has not conceived after 12 months of contraceptive-free intercourse. Twelve months is the lower reference limit for Time to Pregnancy (TTP) by the World Health Organization.[3] a woman over 35 has not conceived after 6 months of contraceptive-free sexual intercourse.

These time intervals would seem to be reversed; this is an area where public policy trumps science. The idea is that for women beyond age 35, every month counts and if made to wait another 6 months to prove the necessity of medical intervention, the problem could become worse. The corollary to this is that, by definition, failure to conceive in women under 35 isn't regarded with the same urgency as it is in those over 35. Alternatively, the NICE guidelines define infertility as failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology.[4] A couple that has tried unsuccessfully to have a child after a certain period of time (often a short period, but definitions vary) is sometimes said to be subfertile, meaning less fertile than a typical couple. Both infertility (see above for definitions) and subfertility are defined as the inability to conceive after a certain period of time (the length of which vary), so often the two terms overlap.
[edit] Primary vs. secondary infertility

Couples with primary infertility have never been able to conceive,[5] while, on the other hand, secondary infertility is difficulty conceiving after already having conceived (and either carried the pregnancy to term or had a miscarriage). Secondary infertility is not present if there has been

a change of partners (this follows tautologically from the convention of speaking of couples, rather than individuals, as being infertile; if there is a change of partners, then a new couple is created, with its own chances to be infertile.)
Specific female causes

For a woman to conceive, certain things have to happen: intercourse must take place around the time when an egg is released from her ovary; the systems that produce eggs and sperm have to be working at optimum levels; and her hormones must be balanced.[16] Some women are infertile because their ovaries do not mature and release eggs. In this case synthetic FSH by injection or Clomid (Clomiphene citrate) via a pill can be given to stimulate follicles to mature in the ovaries. Problems affecting women include endometriosis or damage to the fallopian tubes (which may have been caused by infections such as chlamydia). Other factors that can affect a woman's chances of conceiving include being over- or underweight, or her age as female fertility declines sharply after the age of 35. Sometimes it can be a combination of factors, and sometimes a clear cause is never established. Common causes of infertility of females include:

ovulation problems tubal blockage age-related factors uterine problems previous tubal ligation endometriosis

Specific male causes

The main cause of male infertility is low semen quality.

[edit] Combined infertility

In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance.
[edit] Unexplained infertility Main article: Unexplained infertility

In the US, up to 20% of infertile couples have unexplained infertility.[17] In these cases abnormalities are likely to be present but not detected by current methods. Possible problems

could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility.[18]
Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), physicians may start by prescribing a course of ovarian stimulating medication. The physician may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.

If conservative medical treatments fail to achieve a full term pregnancy, the physician may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques. ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer. Other medical techniques are e.g. tuboplasty, assisted hatching, and Preimplantation genetic diagnosis.

Spermatogenesis Abnormalities
These are male abnormalities that generally become apparent late postnatally after puberty or when reproduction is planned. These condations would not be detected (unless with a genetic history) in prenatal and early postnatal development.

Gonadal Descent
Due to the relative positions of the male (external) and female (internal) gonads and the pathways for their movement, failure of gonad descent is more apparent and common in male cryptorchidism than female undescended ovaries.
Sexually transmitted infections (STI), also previously referred to as sexually transmitted diseases (STD) and venereal diseases (VD), are illnesses that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex. While

in the past, these illnesses have mostly been referred to as STDs or VD, in recent years the term sexually transmitted infections (STIs) has been preferred, as it has a broader range of meaning; a person may be infected, and may potentially infect others, without having a disease. Some STIs can also be transmitted via the use of IV drug needles after its use by an infected person, as well as through childbirth or breastfeeding. Sexually transmitted infections have been well known for hundreds of years.

Prevention:Vaccines are available that protect against some viral STIs, such as Hepatitis A, Hepatitis B, and some types of HPV. Vaccination before initiation of sexual contact is advised to assure maximal protection.Vaccines:
Condoms and female condoms only provide protection when used properly as a barrier, and only to and from the area that it covers. Uncovered areas are still susceptible to many STDs. In the case of HIV, sexual transmission routes almost always involve the penis, as HIV cannot spread through unbroken skin, thus properly shielding the insertive penis with a properly worn condom from the vagina or anus effectively stops HIV transmission. An infected fluid to broken skin borne direct transmission of HIV would not be considered "sexually transmitted", but can still theoretically occur during sexual contact, this can be avoided simply by not engaging in sexual contact when having open bleeding wounds. Other STDs, even viral infections, can be prevented with the use of latex, polyurethane or polyisoprene condoms as a barrier. Some microorganisms and viruses are small enough to pass through the pores in natural skin condoms, but are still too large to pass through latex or synthetic condoms.

Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments (molecular cloning), cells (cell cloning), or organisms. The term also refers to the production of multiple copies of a product such as digital media or software. The term clone is derived from the Ancient Greek word (kln, twig), referring to the process whereby a new plant can be created from a twig. In horticulture, the spelling clon was used until the twentieth century; the final e came into use to indicate the vowel is a "long o" instead of a "short o".[1][2] Since the term entered the popular lexicon in a more general context, the spelling clone has been used exclusively.

Molecular cloning
Molecular cloning refers to the process of making multiple molecules. Cloning is commonly used to amplify DNA fragments containing whole genes, but it can also be used to amplify any DNA sequence such as promoters, non-coding sequences and randomly fragmented DNA. It is used in a wide array of biological experiments and practical applications ranging from genetic fingerprinting to large scale protein production. Occasionally, the term cloning is misleadingly used to refer to the identification of the chromosomal location of a gene associated with a particular phenotype of interest, such as in positional cloning. In practice, localization of the gene to a chromosome or genomic region does not necessarily enable one to isolate or amplify the relevant genomic sequence. To amplify any DNA sequence in a living organism, that sequence must be linked to an origin of replication, which is a sequence of DNA capable of

directing the propagation of itself and any linked sequence. However, a number of other features are needed and a variety of specialised cloning vectors (small piece of DNA into which a foreign DNA fragment can be inserted) exist that allow protein expression, tagging, single stranded RNA and DNA production and a host of other manipulations. Cloning of any DNA fragment essentially involves four steps[3] 1. 2. 3. 4. fragmentation - breaking apart a strand of DNA ligation - gluing together pieces of DNA in a desired sequence transfection - inserting the newly formed pieces of DNA into cells screening/selection - selecting out the cells that were successfully transfected with the new DNA

Although these steps are invariable among cloning procedures a number of alternative routes can be selected, these are summarized as a 'cloning strategy'. Initially, the DNA of interest needs to be isolated to provide a DNA segment of suitable size. Subsequently, a ligation procedure is used where the amplified fragment is inserted into a vector (piece of DNA). The vector (which is frequently circular) is linearised using restriction enzymes, and incubated with the fragment of interest under appropriate conditions with an enzyme called DNA ligase. Following ligation the vector with the insert of interest is transfected into cells. A number of alternative techniques are available, such as chemical sensitivation of cells, electroporation, optical injection and biolistics. Finally, the transfected cells are cultured. As the aforementioned procedures are of particularly low efficiency, there is a need to identify the cells that have been successfully transfected with the vector construct containing the desired insertion sequence in the required orientation. Modern cloning vectors include selectable antibiotic resistance markers, which allow only cells in which the vector has been transfected, to grow. Additionally, the cloning vectors may contain colour selection markers, which provide blue/white screening (alpha-factor complementation) on X-gal medium. Nevertheless, these selection steps do not absolutely guarantee that the DNA insert is present in the cells obtained. Further investigation of the resulting colonies must be required to confirm that cloning was successful. This may be accomplished by means of PCR, restriction fragment analysis and/or DNA sequencing.
Unicellular organisms

Cloning a cell means to derive a population of cells from a single cell. In the case of unicellular organisms such as bacteria and yeast, this process is remarkably simple and essentially only requires the inoculation of the appropriate medium. However, in the case of cell

cultures from multi-cellular organisms, cell cloning is an arduous task as these cells will not readily grow in standard media.

A useful tissue culture technique used to clone distinct lineages of cell lines involves the use of cloning rings (cylinders).[4] According to this technique, a single-cell suspension of cells that have been exposed to a mutagenic agent or drug used to drive selection is plated at high dilution to create isolated colonies; each arising from a single and potentially clonal distinct cell. At an early growth stage when colonies consist of only a few of cells, sterile polystyrene rings (cloning rings), which have been dipped in grease are placed over an individual colony and a small amount of trypsin is added. Cloned cells are collected from inside the ring and transferred to a new vessel for further growth.
Dolly the Sheep

Dolly, a Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult cell. Dolly was formed by taking a cell from the udder of her biological mother. Her embryo was created by taking the cell and inserting it into a sheep ovum. The embryo was then placed inside a female sheep that went through a normal pregnancy.[13] She was cloned at the Roslin Institute in Scotland and lived there from her birth in 1996 until her death in 2003 when she was six. Her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.[14] Dolly was publicly significant because the effort showed that the genetic material from a specific adult cell, programmed to express only a distinct subset of its genes, can be reprogrammed to grow an entirely new organism. Before this demonstration, it had been shown by John Gurdon that nuclei from differentiated cells could give rise to an entire organism after transplantation into an enucleated egg.[15] However, this concept was not yet demonstrated in a mamallian system. Cloning Dolly the sheep had a low success rate per fertilized egg; she was born after 277 eggs were used to create 29 embryos, which only produced three lambs at birth, only one of which lived. Seventy calves have been created and one third of them died young; Prometea took 277 attempts. Notably, although the first clones were frogs, no adult cloned frog has yet been produced from a somatic adult nucleus donor cell. There were early claims that Dolly the Sheep had pathologies resembling accelerated aging. Scientists speculated that Dolly's death in 2003 was related to the shortening of telomeres, DNAprotein complexes that protect the end of linear chromosomes. However, other researchers, including Ian Wilmut who led the team that successfully cloned Dolly, argue that Dolly's early death due to respiratory infection was unrelated to deficiencies with the cloning process.

Dolly, a Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult cell. Dolly was formed by taking a cell from the udder of her biological Family planning is the planning of when to have children,[1] and the use of birth control[2][3] and other techniques to implement such plans. Other techniques commonly used include sexuality education,[3][4] prevention and management of sexually transmitted infections,[3] pre-conception counseling[3] and management, and infertility management.[2]