Traditional Chinese medicine (TCM) is a style of traditional Asian medicine informed by modern medicine but built on a foundation of more than 2,500 years of Chinese medical practice that includes various forms of herbal medicine, acupuncture, massage (tui na), exercise (qigong), and dietary therapy. It is primarily used as a complementary alternative medicine approach. TCM is widely used in China and is becoming increasingly prevalent in Europe and North America.
One of the basic tenets of TCM "holds that the body's vital energy (chi or qi) circulates through channels, called meridians, that have branches connected to bodily organs and functions." Concepts of the body and of disease used in TCM reflect its ancient origins and its emphasis on dynamic processes over material structure, similar to European humoral theory. Scientific investigation has found nohistological or physiological evidence for traditional Chinese concepts such as qi, meridians, and acupuncture points. The TCM theory and practice are not based upon scientific knowledge, and its own practitioners disagree widely on what diagnosis and treatments should be used for any given patient. The effectiveness of Chinese herbal medicine remains poorly researched and documented. There are concerns over a number of potentially toxic plants, animal parts, and mineral Chinese medicinals. A review of cost-effectiveness research for TCM found that studies had low levels of evidence, but so far have not shown benefit outcomes. Pharmaceutical research has explored the potential for creating new drugs from traditional remedies, with few successful results. A Nature editorial described TCM as "fraught withpseudoscience", and said that the most obvious reason why it hasn't delivered many cures is that the majority of its treatments have no logical mechanism of action. Proponents propose that research has so far missed key features of the art of TCM, such as unknown interactions between various ingredients and complex interactive biological systems.
TCM's view of the body places little emphasis on anatomical structures, but is mainly concerned with the identification of functional entities (which regulate digestion, breathing, aging etc.). While health is perceived as harmonious interaction of these entities and the outside world, disease is interpreted as a disharmony in interaction. TCM diagnosis aims to trace symptoms to patterns of an underlying disharmony, by measuring the pulse, inspecting the tongue, skin, and eyes, and looking at the eating and sleeping habits of the person as well as many other things.
The fundamental principles of TCM are based on the Yin-Yang doctrine, the symbolic way of designating opposing forces, and the five element theory that everything in the Universe is dominated and balanced by the five elements, wood, fire, earth, metal and water. The therapeutic mechanism of TCM focuses on enhancing human body's resistance to diseases by improving the inter-connections among self-controlled systems and integrating the human body with the environment. The practice of TCM involves physical therapy such as acupuncture and chemical therapy using materials originating from plants, minerals and animals, while TCM natural products may comprise one or more herbs in the form of decoctions.
In Chinese philosophy, the concept of yin yang sometimes referred to in the west as yin and yang) is used to describe how polar or seemingly contrary forces are interconnected and interdependent in the natural world, and how they give rise to each other in turn. Many natural dualities — e.g. dark and light, female and male, low and high, cold and hot — are thought of as manifestations of yin and yang (respectively).
Yin yang are complementary opposites within a greater whole. Everything has both yin and yang aspects, although yin or yang elements may manifest more strongly in different objects or at different times. Yin yang constantly interacts, never existing in absolute stasis. The concept of yin and yang is often symbolized by various forms of the Taijitu symbol, for which it is probably best known in western cultures. There is a perception (especially in the West) that yin and yang correspond to good and evil. However, Taoist philosophy generally discounts good/bad distinctions as superficial labels, preferring to focus on the idea of balance.
In TCM, there are five diagnostic methods: inspection, auscultation, olfaction, inquiry, and palpation.
Inspection focuses on the face and particularly on the tongue, including analysis of the tongue size, shape, tension, color and coating, and the absence or presence of teeth marks around the edge.
Auscultation refers to listening for particular sounds (such as wheezing). Olfaction refers to attending to body odor. Inquiry focuses on the "seven inquiries", which involve asking the person about the regularity, severity, or other characteristics of: chills, fever, perspiration, appetite, thirst, taste, defecation, urination, pain, sleep, menses, leukorrhea. Palpation which includes feeling the body for tender A-shi points, and the palpation of the wrist pulses as well as various other pulses, and palpation of the abdomen. Examination of the tongue and the pulse are among the principal diagnostic methods in TCM.Certain sectors of the tongue's surface are believed to correspond to the zàng-fŭ. For example, teeth marks on one part of the tongue might indicate aproblem with the Heart, while teeth marks on another part of the tongue might indicate a problem with the Liver. Pulse palpation involves measuring the pulse both at a superficial and at a deep level at three different locations on the radial artery (Cun, Guan, Chi, located two fingerbreadths from the wrist crease, one fingerbreadth from the wrist crease, and right at the wrist crease, respectively, usually palpated with the index, middle and ring finger) of each, for a total of twelve pulses, all of which are thought to correspond with certain zàng-fŭ. The pulse is examined for several characteristics including rhythm, strength and volume, and described with qualities like "floating, slippery, bolstering-like, feeble, thready and quick"; each of these qualities indicate certain disease patterns. Learning TCM pulse diagnosis can take several years.
Chinese medicine therapies
Anti-inflammatory medications are a class of drugs that reduce inflammation. They also work to reduce the swelling of the inflamed tissue, reduce fever (antipyretic effect) and alleviate pain (analgesic effect). Anti-inflammatory drugs represent an important part of analgesics (painkillers), while other drugs that alleviate pain, such as opioids or simple analgesics, only block the perception of pain.
Anti-inflammatory drugs have been traditionally divided into two major categories:
Non-steroidal anti-inflammatory drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own COX enzyme synthesizes prostaglandins (Pic. 2), creating inflammation. In whole the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the pain. NSAIDs are used in the treatment of a variety of symptoms and conditions, ranging from mild to moderate pain-reliever to their use in the reduction of heart attacks and strokes. Their anti-inflammatory properties make them most useful in the management of disorders in which pain is related to the intensity of the inflammatory process.
When conditions related to fertility are concerned, NSAIDs can be used in the treatment of primary dysmenorrhea (painful menstruation), endometriosis, menorrhagia (prolonged or heavy menstrual bleeding), pain associated with an intra-uterine device (IUD) or with medical abortion, prostatic diseases, and as a symptomatic pain-relieving medication in a wide variety of inflammatory conditions affecting the genital tract.
Endometrial ablation is the procedure in which is removed or destroyed the endometrium (the inner layer of uterus) and superficial myometrium (the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells). The main purpose is to destroy the basal layer of endometrium and inhibit its regeneration, hence preventing blood loss during menses. Women who suffer from excessive menstrual bleeding (Pic. 1) and who have failed medical therapy and do not wish to undergo a hysterectomy (surgical removal of the uterus) are reccomended to undergo endometrial ablation.
Endometrial ablation has been explored and many devices and techniques have been developed and have been found to be effective. The procedure is almost always performed as an outpatient treatment, either at the hospital, ambulatory surgery center, or physician office. The endometrial ablation procedure is primarily performed while patients are under local and/or light sedative anesthesia, or if necessary, general or spinal anesthesia. Patients normally leave the treatment facility within one hour following the procedure and generally spend one day resting at home, before returning to the activities of daily living.
A number of treatment options are available (Pic. 2):
Endometrial Ablation System (Minerva Surgical), Minerva works by generating heat from plasma energy that is created and contained inside a leak-proof ablation array that takes the shape of the uterine cavity. The hot membrane surface of the array ablates (destroys) the endometrium.
The Minerva procedure is the fastest FDA (Food and Drug Administration) approved treatment, average procedure time is 3.1 minutes from device insertion to removal, and is usually performed under local and/or conscious sedation anesthesia. Most patients leave the treatment center within one hour of treatment.
Endometrial Ablation System, utilizes a metallized mesh electrode array that is introduced into the uterine cavity, applying bipolar electrical energy that creates heat to ablate (destroy) the endometrium.
The Novasure average procedure time is 5 minutes from device insertion to removal and is usually performed under local and/or conscious sedation anesthesia. Most patients leave the treatment center within one hour of treatment.
The Genesys HTA
Hydro-Thermal Ablation System, uses a hysteroscope device (Pic. 3) which is inserted into the uterus through the cervical canal, to help doctors safely confirm proper probe placement and to see the area they are treating. In this procedure, the doctor looks at the inside of the uterus with the hysteroscope and then fills the uterus with saline fluid. The fluid is then slowly heated and the lining of the uterus is burned so that menstrual bleeding periods become less heavy and, in some cases, even stops. The fluid is then cooled and removed by special tubing to protect the external areas of the body from any burns.
The average procedure time is 26 minutes.
The Her Option
Endometrial Ablation System, is a treatment that creates sub-zero temperatures to freeze and ablate the endometrium. Following the application of local anesthetic around the cervix, a physician uses ultrasound to guide the placement of a cryoprobe (a long slender pointed surgical instrument, used to apply extreme cold to tissues) to the right uterine horn (cornua). The cryoprobe is activated, reducing its temperature to minus 60°C. The cryoprobe is kept in place while ice is formed in the uterine cavity, under ultrasound observation. Once the appropriate time has passed and/or the appropriate depth of ice has been achieved, the cryoprobe is warmed to 37°C. The cryoprobe is then repositioned to the untreated left uterine horn and the procedure is repeated. Finally, the cryoprobe is warmed and removed.
Transcervical Resection of the Endometrium (TCRE) or Loop Resection with Rollerball
Ablation as it is commonly called, utilizes a hysteroscope, through which a bi-polar radio frequency electrocautery cutting loop is deployed to resect (remove) the superficial endometrium, followed by a bi-polar radio frequency rollerball tool to ablate the remaining underlying endometrium via cauterization. It is a proven procedure, being a day-care procedure with rapid recovery.
The 'Thermachoice III '- balloon
This system utilized a heated saline filled balloon which was inserted into the uterine cavity to ablate the endometrium. The fluid was safely contained in a flexible and non-allergenic Silastic membrane that conformed to most uterine cavity shapes and sizes.
After the procedure, the endometrium heals by scarring over, thus reducing or eliminating future uterine bleeding. The patient's hormonal functions will remain unaffected because the ovaries are left intact.
Laparoscopic myometrial electrocoagulation is a procedure, which main purpose is to induce localised coagulation (the process by which blood changes from a liquid to a gel, forming a blood clot) and necrosis (a form of cell injury which results in the premature death of cells).
The key element in laparoscopic surgery is the use of a laparoscope, a long fiber optic cable system which allows viewing of the pelvic area by snaking the cable from a more distant, but more easily accessible location- in this case the navel (Pic. 1). At 1-2 cm intervals the needle punctures are done into to uterus to deliver unipolar or bipolar coagulation current (the application of a high-frequency alternating polarity, electrical current to biological tissue as a means to clotting the blood).
Adenomyosis is a gynecologic medical condition characterized by the abnormal presence of endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). Thanks to laparoscopic myometrial electrocoagulation endometrial tissue localised in myometrium than became shrinking and the activity is lowered and women do not suffer from symptoms caused by adenomyosis.
Norethisterone acetate (abbreviated as NETA), or norethindrone acetate, is a progestin which is used in hormone replacement therapy, and to treat gynecological disorders, especially adenomyosis (the inner lining of the uterus breaks through the muscle wall of the uterus) and endometriosis (endometrial cells are found growing outside of the uterus). NETA is also used as a hormonal contraceptive in combination with estrogen, in the treatment of gynecological disorders such as abnormal uterine bleeding.
It causes a hypoestrogenism (low level of estrogen in bloodstream) by suppressing hormones that stimulate the gonads, or sex glands, to carry out their reproductive or endocrine functions), inhibiting ovulation, and developing amenorrhea (the absence of a menstrual period in a woman of reproductive age) with eventual partial or complete wasting of inner layer of the uterus (endometrial atrophy).
NETA is a prodrug of norethisterone in the body.Upon oral ingestion, it is rapidly converted into norethisterone by esterases during intestinal and first-pass hepatic metabolism. Hence, as a prodrug of norethisterone, NETA has essentially the same effects, acting as a potent progestogen with additional weak androgenic and estrogenic activity.
Egg donation is the process by which a woman donates eggs for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation typically involves IVF technology, with the eggs being fertilized in the laboratory; more rarely, unfertilized eggs may be frozen and stored for later use. Egg donation is a third party reproduction as part of ART.
Egg donor may have several reasons for donate her eggs:
First step is choosing the egg donor by a recipient from the profiles on or clinic databases (or, in countries where donors are required to remain anonymous, they are chosen by the recipient's doctor based on recipient woman’s desired trait). This is due to the fact that all of the mentioned examinations are expensive and the agencies/clinics must first confirm that a match is possible or guaranteed before investing in the process.
Each egg donor is first referred to a psychologist who will evaluate if she is mentally prepared to undertake and complete the donation process. These evaluations are necessary to ensure that the donor is fully prepared and capable of completing the donation cycle in safe and success manner. The donor is then required to undergo a thorough medical examination, including a pelvic exam, blood tests to check hormone levels and to test for infectious diseases, Rh factor, blood type, and drugs and an ultrasound to examine her ovaries, uterus and other pelvic organs. A family history of approximately the past three generations is also required, meaning that adoptees are usually not accepted because of the lack of past health knowledge. Genetic testing is also usually done on donors to ensure that they do not carry mutations (e.g., cystic fibrosis) that could harm the resulting children; however, not all clinics automatically perform such testing and thus recipients must clarify with their clinics whether such testing will be done. During the process, which usually takes several months, the donor must abstain from alcohol, sexual intercourse, cigarettes, and drugs, both prescription and non-prescription.
Once the screening is complete and a legal contract signed, the donor will begin the donation cycle, which typically takes between three and six weeks. An egg retrieval procedure comprises both the egg donor's cycle and the recipient's cycle. Birth control pills are administered during the first few weeks of the egg donation process to synchronize the donor's cycle with her recipient's, followed by a series of injections which halt the normal functioning of the donor's ovaries. These injections may be self-administered on a daily basis for a period of one to three weeks. Next, FSH is given to the donor to stimulate egg production and increases the number of mature eggs produced by the ovaries. Throughout the cycle the donor is monitored often by a physician using blood tests and ultrasound exams to determine the donor's reaction to the hormones and the progress of follicle growth.
Once the doctor decides the follicles are mature, the doctor will establish the date and time for the egg retrieval procedure. Approximately 36 hours before retrieval, the donor must administer one last injection of hCG to ensure that her eggs are ready to be harvested. The egg retrieval itself is a minimally invasive surgical procedure lasting 20-30 minutes, performed under sedation (but sometimes without any). A small ultrasound-guided needle is inserted through the vagina to aspirate the follicles in both ovaries, which extracts the eggs. After resting in a recovery room for an hour or two, the donor is released. Most donors resume regular activities by the next day.
Laws by state
The legal status and compensation of egg donation has several models across states with examples:
During ICSI just one sperm is injected directly into the egg cytoplasm using a micromanipulative apparatus that transforms imperfect hand movements into fine and precise movements of micromanipulation tools.
Intracytoplasmic Sperm Injection (ICSI) is an assisted reproductive technique (ART) initially developed by Dr. Gianpiero D. Palermo in 1993 to treat male infertility. It is most commonly used in conjunction with in vitro fertilization (IVF). Following IVF procedure, the physician places the fertilized egg into the female’s uterus for implantation. Sperm are obtained by the same methods as with IVF: either through masturbation, by using a collection condom, or by surgically removing sperm from a testicle through a small incision (MESA, TESE). The females are treated with fertility medications for approximately two weeks prior to oocyte retrieval to stimulate superovulation, where the ovaries produce multiple oocytes rather than the normal one oocyte. The oocytes are retrieved by either laparoscopy, or more commonly, transvaginal oocyte retrieval. In the latter procedure, the physician inserts a thin needle through the cervix, guided by a sonogram and pierces the vaginal wall and then the ovaries to extract several mature ova. Before the embryologist can inject the sperm into the oocyte, the sperm must be prepared by washing and exposing it to various chemicals to slow the sperm movement and prevent it from sticking to the injection plate. Also, the oocytes are treated with hyaluronidase to single out the oocyte ready for fertilization by the presence of the first polar body. Then, one prepared sperm is injected into an oocyte with a thin needle. Often, embryologists try to fertilize several eggs so they can implant more than one into the uterus and increase the chance of at least one successful pregnancy. This also allows them to save extra embryos, using cryopreservation, in case later IVF rounds are needed.
After the embryologist manually fertilizes the oocytes, they are incubated for sixteen to eighteen hours and develop into a pronucleate eggs (successfully fertilized eggs about to divide into an embryo). The egg then grows for one to five days in the laboratory before the physician places it in the female’s uterus for implantation.
The chance of fertilization increases dramatically with ICSI compared to simply mixing the oocytes and sperm in a Petri dish and waiting for fertilization to occur unaided (classical IVF procedure). Studies have shown that successful fertilizations occur 50% to 80% of the time. Since the introduction of ICSI, intrauterine insemination (IUI) has decreased in popularity by 80%.See full description of ICSI
Sperm donation is the donation by a male (known as a sperm donor) of his sperm (known as donor sperm), principally for the purpose of inseminating a female who is not his sexual partner. Sperm donation is a form of third party reproduction including sperm donation, oocyte donation, embryo donation, surrogacy, or adoption. Number of births per donor sample will depend on the actual ART method used, the age and medical condition of the female bearing the child, and the quality of the embryos produced by fertilization. Donor sperm is more commonly used for artificial insemination (IUI or ICI) than for IVF treatments. This is because IVF treatments are usually required only when there is a problem with the female conceiving, or where there is a “male factor problem” involving the female's partner. Donor sperm is also used for IVF in surrogacy arrangements where an embryo may be created in an IVF procedure using donor sperm and this is then implanted in a surrogate. In a case where IVF treatments are employed using donor sperm, surplus embryos may be donated to other women or couples and used in embryo transfer procedures.
On the other hand, insemination may also be achieved by a donor having sexual intercourse with a female for the sole purpose of initiating conception. This method is known as natural insemination.
Donor sperm and fertility treatments using donor sperm may be obtained at a sperm bank or fertility clinic. Here, the recipient may select donor sperm on the basis of the donor's characteristics, e.g. looks, personality, academic ability, race, and many other factors. Sperm banks or clinics may be subject to state or professional regulations, including restrictions on donor anonymity and the number of offspring that may be produced, and there may be other legal protections of the rights and responsibilities of both recipient and donor. Some sperm banks, either by choice or regulation, limit the amount of information available to potential recipients; a desire to obtain more information on donors is one reason why recipients may choose to use a known donor and/or private donation.
A sperm donor will usually donate sperm to a sperm bank under a contract, which typically specifies the period during which the donor will be required to produce sperm, which generally ranges from 6–24 months depending on the number of pregnancies which the sperm bank intends to produce from the donor. Donors may or may not be paid for their samples, according to local laws and agreed arrangements. Even in unpaid arrangements, expenses are often reimbursed. Depending on local law and on private arrangements, men may donate anonymously or agree to provide identifying information to their offspring in the future. Private donations facilitated by an agency often use a "directed" donor, when a male directs that his sperm is to be used by a specific person. Non-anonymous donors are also called known donors, open donors or identity disclosure donors.
A sperm donate must generally meet specific requirements regarding age (most often up to 40) and medical history. Potential donors are typically screened for genetic diseases, chromosomal abnormalities and sexually transmitted infections that may be transmitted through sperm. The donor's sperm must also withstand the freezing and thawing process necessary to store and quarantine the sperm. Samples are stored for at least 6 months after which the donor will be re-tested for sexually transmitted infections. This is to ensure no new infections have been acquired or have developed during the period of donation. If the result is negative, the sperm samples can be released from quarantine and used in treatments.
Preparing the samples
A sperm donor is usually advised not to ejaculate for two to three days before providing the sample, to increase sperm count and to maximize the conception rate. A sperm donor produces and collects sperm by masturbation or during sexual intercourse with the use of a collection condom.
Sperm banks and clinics usually "wash" the sperm sample to extract sperm from the rest of the material in the semen. A cryoprotectant semen extender is added if the sperm is to be placed in frozen storage in liquid nitrogen, and the sample is then frozen in a number of vials or straws. One sample will be divided into 1-20 vials or straws depending on the quantity of the ejaculate and whether the sample is washed or unwashed. Following the necessary quarantine period, the samples are thawed and used to inseminate women through artificial insemination or other ART treatments. Unwashed samples are used for ICI treatments, and washed samples are used in IUI and IVF procedures.
Anonymous sperm donation occurs where the child and/or receiving couple will never learn the identity of the donor, and non-anonymous when they will. Non-anonymous sperm donors are, to a substantially higher degree, driven by altruistic motives for their donations.
Even with anonymous donation, some information about the donor may be released to the female/couple at the time of treatment. Limited donor information includes height, weight, eye, skin and hair color. In Sweden, this is all the information a receiver gets. In the US, on the other hand, additional information may be given, such as a comprehensive biography and sound/video samples.
Information made available by a sperm bank will usually include the race, height, weight, blood group, health, and eye color of the donor. Sometimes information about his age, family history and educational achievements will also be given.
Different factors motivate individuals to seek sperm from outside their home state. For example, some jurisdictions do not allow unmarried women to receive donor sperm. Jurisdictional regulatory choices as well as cultural factors that discourage sperm donation have also led to international fertility tourism and sperm markets.
A sperm donor is generally not intended to be the legal or de jure father of a child produced from his sperm. Depending on the jurisdiction and its laws, he may or may not later be eligible to seek parental rights or be held responsible for parental obligations. Generally, a male who provides sperm as a sperm donor gives up all legal and other rights over the biological children produced from his sperm. However, in private arrangements, some degree of co-parenting may be agreed, although the enforceability of those agreements varies by jurisdiction.
Laws prohibits sperm donation in several countries: Algeria, Bahrain, Costa Rica, Egypt, Hong Kong, Jordan, Lebanon, Lithuania, Libya, Maldives, Oman, Pakistan, Philippines, Qatar, Saudi Arabia, Syria, Tajikistan, Tunisia, Turkey, UnitedArab Emirates, and Yemen.See full description of Sperm donation
In vitro fertilization (IVF) is a process by which an egg is fertilised by sperm outside the body: in vitro . The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova (egg or eggs) from the woman's ovaries and letting sperm fertilise them in a liquid in a laboratory. The fertilised egg (zygote) is cultured for 2–6 days in a growth medium and is then implanted in the same or another woman's uterus, with the intention of establishing a successful pregnancy.
IVF techniques can be used in different types of situations. It is a technique of assisted reproductive technology for treatment of infertility. IVF techniques are also employed in gestational surrogacy, in which case the fertilised egg is implanted into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. In some situations, donated eggs or sperms may be used. Some countries ban or otherwise regulate the availability of IVF treatment, giving raise to fertility tourism. Restrictions on availability of IVF include to single females, to lesbians and to surrogacy arrangements. Due to the costs of the procedure, IVF is mostly attempted only after less expensive options have failed.
The first successful birth of a "test tube baby", Louise Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF where no stimulation was made. Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. With egg donation and IVF, women who are past their reproductive years or menopause can still become pregnant. Adriana Iliescu held the record as the oldest woman to give birth using IVF and donated egg, when she gave birth in 2004 at the age of 66, a record passed in 2006.
Classically, the diagnosis of adenomyosis has only been possible on a hysterectomy specimen, usually in women in their late fourth and fifth decades,and, therefore, evaluating any relationship with infertility was simply not possible. As a consequence, to this day, no epidemiologic data exists linking adenomyosis to a state of subfertility. Today, new imaging techniques have enabled a noninvasive diagnosis at a much earlier time and a number of single-case or small series reports have appeared showing that medical,surgical, or combined treatment can restore fertility in women with adenomyosis, an indirect proof of an association. At the functional level, several anomalies found in the so-called junctional zone, or inner myometrium, in adenomyosis patients have been shown to be associated with poor reproductive performance, mainly through perturbed uterine peristalsis. Additional evidence for an association comes from experimental data: in baboons, adenomyosis is associated with lifelong primary infertility, as well as to endometriosis. Finally, indirect proof comes from studies of the eutopic and ectopic endometrium in women with adenomyosis proving the existence of an altered endometrial function and receptivity. In conclusion, sufficient indirect proofexists linking adenomyosis to infertility to warrant systematic clinical studies.