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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Drugs used during pregnancy can have temporary or permanent effects on the fetus. Anything (including drugs) that can cause permanent deformities in the fetus are labeled as teratogens. In the U.S., drugs were classified into categories A, B, C, D and X based on the Food and Drug Administration (FDA) rating system to provide therapeutic guidance based on potential benefits and fetal risks. Drugs, including some multivitamins, that have demonstrated no fetal risks after controlled studies in humans are classified as Category A. On the other hand, drugs like thalidomide with proven fetal risks that outweigh all benefits are classified as Category X.
Pseudocyesis is not known to have a direct underlying physical cause and there are no general recommendations regarding treatment with medications. In some cases, however, the patient may be given medications for such symptoms as the cessation of menstruation. When some patients with pseudocyesis have underlying psychological problems, they should be referred to a psychotherapist for the treatment of these problems. It is important at the same time, however, for the treating professional not to minimize the reality of the patient's physical symptoms. The treatment that has had the most success is demonstrating to the patient that she is not really pregnant by the use of ultrasound or other imaging techniques.
No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options: watchful waiting, medical management, and surgical treatment. With no treatment (watchful waiting), most miscarriages (65–80%) will pass naturally within two to six weeks. This treatment avoids the possible side effects and complications of medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage. Medical treatment usually consists of using misoprostol (a prostaglandin) to contract the uterus, expelling remaining tissue out of the cervix. This works within a few days in 95% of cases. Vacuum aspiration or sharp curettage can be used, though vacuum aspiration is lower-risk and more common.
In delayed or incomplete miscarriage, treatment depends on the amount of tissue remaining in the uterus. Treatment can include surgical removal of the tissue with vacuum aspiration or misoprostol. Some organizations recommend delaying sexual relations immediately after a miscarriage to prevent infection.
Nutrition during pregnancy is important to ensure healthy growth of the fetus. Nutrition during pregnancy is different from the non-pregnant state. There are increased energy requirements and specific micronutrient requirements. Women benefit from education to encourage a balanced energy and protein intake during pregnancy. Some women may need professional medical advice if their diet is affected by medical conditions, food allergies, or specific religious/ ethical beliefs.
Adequate periconceptional (time before and right after conception) folic acid (also called folate or Vitamin B) intake has been shown to decrease the risk of fetal neural tube defects, such as spina bifida. The neural tube develops during the first 28 days of pregnancy, a urine pregnancy test is not usually positive until 14 days post-conception, explaining the necessity to guarantee adequate folate intake before conception. Folate is abundant in green leafy vegetables, legumes, and citrus. In the United States and Canada, most wheat products (flour, noodles) are fortified with folic acid.
DHA omega-3 is a major structural fatty acid in the brain and retina, and is naturally found in breast milk. It is important for the woman to consume adequate amounts of DHA during pregnancy and while nursing to support her well-being and the health of her infant. Developing infants cannot produce DHA efficiently, and must receive this vital nutrient from the woman through the placenta during pregnancy and in breast milk after birth.
Several micronutrients are important for the health of the developing fetus, especially in areas of the world where insufficient nutrition is common. Women living in low and middle income countries are suggested to take multiple micronutrient supplements containing iron and folic acid. These supplements have been shown to improve birth outcomes in developing countries, but do not have an effect on perinatal mortality. Adequate intake of folic acid, and iron is often recommended. In developed areas, such as Western Europe and the United States, certain nutrients such as Vitamin D and calcium, required for bone development, may also require supplementation. Vitamin E supplementation has not been shown to improve birth outcomes. Zinc supplementation has been associated with a decrease in preterm birth, but it is unclear whether it is causative. Daily iron supplementation reduces the risk of maternal anemia. Studies of routine daily iron supplementation for pregnant women found improvement in blood iron levels, without a clear clinical benefit. The nutritional needs for women carrying twins or triplets. are higher than those of women carrying one baby.
Women are counseled to avoid certain foods, because of the possibility of contamination with bacteria or parasites that can cause illness. Careful washing of fruits and raw vegetables may remove these pathogens, as may thoroughly cooking leftovers, meat, or processed meat. Unpasteurized dairy and deli meats may contain "Listeria," which can cause neonatal meningitis, stillbirth and miscarriage. Pregnant women are also more prone to "Salmonella" infections, can be in eggs and poultry, which should be thoroughly cooked. Cat feces and undercooked meats may contain the parasite Toxoplasma gondii and can cause toxoplasmosis. Practicing good hygiene in the kitchen can reduce these risks.
Women are also counseled to eat seafood in moderation and to eliminate seafood known to be high in mercury because of the risk of birth defects. Pregnant women are counseled to consume caffeine in moderation, because large amounts of caffeine are associated with miscarriage. However, the relationship between caffeine, birthweight, and preterm birth is unclear.
Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. According to ESHRE recommendations, couples with an estimated live birth rate of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, and metformin.
Early treatment of an ectopic pregnancy with methotrexate is a viable alternative to surgical treatment which was developed in the 1980s. If administered early in the pregnancy, methotrexate terminates the growth of the developing embryo; this may cause an abortion, or the developing embryo may then be either resorbed by the woman's body or pass with a menstrual period. Contraindications include liver, kidney, or blood disease, as well as an ectopic embryonic mass > 3.5 cm.
Also, it may lead to the inadvertent termination of an undetected intrauterine pregnancy, or severe abnormality in any surviving pregnancy. Therefore, it is recommended that methotrexate should only be administered when hCG has been serially monitored with a rise less than 35% over 48 hours, which practically excludes a viable intrauterine pregnancy.
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), a course of ovarian stimulating medication maybe used. The physician or WHNP 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 or WHNP 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 or WHNP 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.
If bleeding has already occurred, surgical intervention may be necessary. However, whether to pursue surgical intervention is an often difficult decision in a stable patient with minimal evidence of blood clot on ultrasound.
Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected Fallopian and remove only the pregnancy (salpingostomy) or remove the affected tube with the pregnancy (salpingectomy). The first successful surgery for an ectopic pregnancy was performed by Robert Lawson Tait in 1883. It is estimated that an acceptable rate of PULs that eventually undergo surgery is between 0.5 and 11%.
Autotransfusion of a woman's own blood as drained during surgery may be useful in those who have a lot of bleeding into their abdomen.
Published reports that a re-implanted embryo survived to birth were debunked as false.
Physicians can reduce the risk of OHSS by monitoring of FSH therapy to use this medication judiciously, and by withholding hCG medication.
Cabergoline confers a significant reduction in the risk of OHSS in high risk women according to a Cochrane review of randomized studies, but the included trials did not report the live birth rates or multiple pregnancy rates. Cabergoline, as well as other dopamine agonists, might reduce the severity of OHSS by interfering with the VEGF system. A systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity of OHSS, without compromising pregnancy outcomes.
The risk of OHSS is smaller when using GnRH antagonist protocol instead of GnRH agonist protocol for suppression of ovulation during ovarian hyperstimulation. The underlying mechanism is that, with the GnRH antagonist protocol, initial follicular recruitment and selection is undertaken by endogenous endocrine factors prior to starting the exogenous hyperstimulation, resulting in a smaller number of growing follicles when compared with the standard long GnRH agonist protocol.
A Cochrane review found administration of hydroxyethyl starch decreases the incidence of severe OHSS. There was insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of intravenous albumin versus cryopreservation. Also, "coasting", which is ovarian hyperstimulation without induction of final maturation, does not significantly decrease the risk of OHSS.
Variable success rate with treatment, very few controlled studies, mostly case reports. Treatment success strongly tends to diminish with age and degree of elevation of FSH.
- Donor oocyte. Oocyte donation is the most successful method for producing pregnancy in perimenopausal women. In the UK the use of donor oocytes after natural menopause is controversial. A 1995 study reported that women age fifty or higher experience similar pregnancy rates after oocyte donation as younger women. They are at equal risk for multiple gestation as younger women. In addition, antenatal complications were experienced by the majority of patients, and that high risk obstetric surveillance and care is vital.
- Natural or Mini-IVF, but without the use of hCG to trigger ovulation, instead the GnRH agonist Synarel (nafarelin acetate) in a diluted form is taken as a nasal spray to trigger ovulation. Human chorionic gonadotropin (hCG) has a long half life and may stimulate (luteinize) small follicles prematurely and cause them to become cysts. Whereas nafarelin acetate in a nasal spray induces a short lived LH surge that is high enough to induce ovulation in large follicles, but too short lived to adversely affect small follicles. This increases the likelihood of the small follicles and oocytes therein developing normally for upcoming cycles and also allows the woman to cycle without taking a break and consequently increases the probability of conception in poor ovarian reserve women and advanced reproductive aged women.
- Pretreatment with 50 mcg ethinylestradiol three times a day for two weeks, followed by recombinant FSH 200 IU/day subcutaneously. Ethinylestradiol treatment was maintained during FSH stimulation. When at least one follicle reached 18mm in diameter and serum estradiol was greater or equal to 150 pg/ML ovulation was induced with an intramuscular injection of 10,000 IU of hCG (human chorionic gonadotropin hormone). For luteal phase support 5,000 IU of hCG was administered every 72 hours. Out of 25 patients 8 ovulated and 4 became pregnant. In the control group there were no ovulations. The patients ranged in age between 24 and 39 years with an average age of 32.7. All women had amenorrhea for at least 6 months (average 16.75 months) and FSH levels greater or equal than 40 mIU/mL (average FSH 68 mIU/ML). The researchers believe this protocol would work for women in early post menopause as well.
- Ethinylestradiol or other synthetic estrogens along with luteal phase progesterone (twice daily 200 mg vaginal suppositories) and estradiol support. Ethinylestradiol lowers high FSH levels which then, it is theorized, up regulates FSH receptor sites and restores sensitivity to FSH. Ethinylestradiol also has the advantage that it does not interfere with the measurement of serum levels of endogenous estradiol. During the luteal phase the FSH levels should be kept low for subsequent cycles, thus the phase is supplemented with 4 mg oral estradiol. Since conception may have occurred estradiol is used instead of the synthetic ethinylestradiol.
- Cyclical hormone replacement therapy.
- The following protocols have shown promise: high dose gonadoropins, flare up GnRH-a protocol (standard or microdose), stop protocols, short protocol, natural cycle or modified natural cycle and low dose hCG during the beginning of the stimulation protocol.
- Gonadotropin-releasing hormone agonist/antagonist conversion with estrogen priming (AACEP) protocol. Fisch, Keskintepe and Sher report 35% (14 out of 40) ongoing gestation in women with elevated FSH levels (all women had prior IVF and poor quality embryos); among women aged 41–42 the ongoing gestation rate was 19% (5 out of 26).
- DHEA: Recent clinical trial by the Center for Human Reproduction in New York showed significant effectiveness. Leonidas and Eudoxia Mamas report six cases of premature ovarian failure. After two to six months of treatment with DHEA (Two 25 mg capsules daily in five cases and three 25 mg capsules daily in one case.) all women conceived. One delivered via C-section, one aborted at 7 weeks and the remaining four were reported at 11 to 27 weeks gestation. Ages were from 37 to 40. FSH levels were from 30 to 112 mIU/mL. Ammenorhea ranged from 9 to 13 months. In addition, there is strong evidence that continuous micronized DHEA 25 mg TID reduces miscarriage and aneuploidy rates, especially above age 35.
- Glucocorticoid therapy. A recent (2007) randomized double blind study done in Egypt reported a statistically significant theurapeutic effect with dexamethasone pretreatment. Fifty-eight women with idiopathic premature ovarian failure and normal karyotype were divided into two groups of twenty-nine. The control group received placebo for twenty-eight days and then GnRH agonists plus gonadotropin therapy (hMG). The treatment group received dexamethasone for twenty-eight days (6 mg/ day) and then GnRH agonists plus gonadotropin therapy (hMG). (In both groups after the first twenty-eight days, and concurrent with the GnRH agonist treatment, the placebo or dexamethasone was gradually tapered off over ten days.) The treatment group had six ovulations and two pregnancies (p value of .02). The control group had three ovulations and no pregnancies.
- A combined pentoxifylline-tocopherol treatment has been reported effective in improving uterine parameters in women with POF undergoing IVF with donor oocytes (IVF-OD). Three women with uterine hormonoresistance despite high estradiol (E2) plasma levels received treatment with 800 mg pentoxifylline and 1000 IU of vitamin E for at least nine months. Three frozen-thawed embryo transfers (ETs) resulted in two viable pregnancies. Mean endometrial thickness increased from 4.9 mm (with thin uterine crosses) to 7.4 mm with nice uterine crosses. This treatment protocol has also reversed some cases of iatrogenic POF caused by full body radiation treatment.
The routine administration of antibiotics to all women with threatened preterm labor reduces the risk of the baby to get infected with group B streptococcus and has been shown to reduce related mortality rates.
When membranes rupture prematurely, obstetrical management looks for development of labor and signs of infection. Prophylactic antibiotic administration has been shown to prolong pregnancy and reduced neonatal morbidity with rupture of membranes at less than 34 weeks. Because of concern about necrotizing enterocolitis, amoxicillin or erythromycin has been recommended, but not amoxicillin + clavulanic acid (co-amoxiclav).
A number of medications may be useful to delay delivery including: NSAIDs, calcium channel blockers, beta mimetics, and atosiban. Tocolysis rarely delays delivery beyond 24–48 hours. This delay however may be sufficient to allow the pregnant woman to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and β2-agonist drugs delay by 48 hours but carry more side effects. Magnesium sulfate does not appear to be useful and may be harmful when used for this purpose.
Treatment of OHSS depends on the severity of the hyperstimulation.
Mild OHSS can be treated conservatively with monitoring of abdominal girth, weight, and discomfort on an outpatient basis until either conception or menstruation occurs. Conception can cause mild OHSS to worsen in severity.
Moderate OHSS is treated with bed rest, fluids, and close monitoring of labs such as electrolytes and blood counts. Ultrasound may be used to monitor the size of ovarian follicles. Depending on the situation, a physician may closely monitor a women's fluid intake and output on an outpatient basis, looking for increased discrepancy in fluid balance (over 1 liter discrepancy is cause for concern). Resolution of the syndrome is measured by decreasing size of the follicular cysts on 2 consecutive ultrasounds.
Aspiration of accumulated fluid (ascites) from the abdominal/pleural cavity may be necessary, as well as opioids for the pain. If the OHSS develops within an IVF protocol, it can be prudent to postpone transfer of the pre-embryos since establishment of pregnancy can lengthen the recovery time or contribute to a more severe course. Over time, if carefully monitored, the condition will naturally reverse to normal – so treatment is typically supportive, although a woman may need to be treated or hospitalized for pain, paracentesis, and/or intravenous hydration.
The uterine curettage is generally done under the effect of anesthesia, preferably spinal anesthesia in hemodynamically stable patients. The advantages of spinal anesthesia over general anesthesia include ease of technique, favorable effects on the pulmonary system, safety in patients with hyperthyroidism and non-tocolytic pharmacological properties. Additionally, by maintaining patient’s consciousness one can diagnose the complications like uterine perforation, cardiopulmonary distress and thyroid storm at an earlier stage than when the patient is sedated or is under general anesthesia.
Hydatidiform moles should be treated by evacuating the uterus by uterine suction or by surgical curettage as soon as possible after diagnosis, in order to avoid the risks of choriocarcinoma. Patients are followed up until their serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level. Invasive or metastatic moles (cancer) may require chemotherapy and often respond well to methotrexate. As they contain paternal antigens, the response to treatment is nearly 100%. Patients are advised not to conceive for half a year after hCG levels have normalized. The chances of having another molar pregnancy are approximately 1%.
Management is more complicated when the mole occurs together with one or more normal fetuses.
Most people develop symptoms of estrogen deficiency, including vasomotor flushes and vaginal dryness, both of which respond to hormone replacement therapy. There are several contraindications of estrogen supplement, including smokers over 35 years of age, uncontrolled hypertension, uncontrolled diabetes mellitus, or history of thromboemboli events.
Women younger than 40 year with primary ovarian insufficiency benefit from physiologic replacement of hormones. Most authorities recommend that this hormone replacement continue until age 50 years, the normal age of menopause. The leading hormone replacement regimen recommended involves the administration of estradiol daily by either skin patch or vaginal ring. This approach reduces the risk of pulmonary embolism and deep venous thrombosis by avoiding the first pass effect on the liver that is induced by oral estrogen therapy. To avoid the development of endometrial cancer young women taking estradiol replacement need also to take a progestin in a regular cyclic fashion. The most evidence supports the use of medroxyprogesterone acetate per day for days one through 12 of each calendar month. This will induce regular and predictable menstrual cycles. It is important that women taking this regimen keep a menstrual calendar. If the next expected menses is late it is important to get a pregnancy test. It this is positive, the woman should stop taking the hormone replacement. Approximately 5 to 10% of women with confirmed primary ovarian insufficiency conceive a pregnancy after the diagnosis without medical intervention.
The transdermal estradiol patch is commonly recommended due to several advantages. It provides the replacement by steady infusion rather than by bolus when taking daily pills. It also avoids the first-pass effect in the liver.
Treatment depends on the amount of blood loss and the status of the fetus. If the fetus is less than 36 weeks and neither mother or fetus is in any distress, then they may simply be monitored in hospital until a change in condition or fetal maturity whichever comes first.
Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother is in distress. Blood volume replacement to maintain blood pressure and blood plasma replacement to maintain fibrinogen levels may be needed. Vaginal birth is usually preferred over Caesarean section unless there is fetal distress. Caesarean section is contraindicated in cases of disseminated intravascular coagulation. People should be monitored for 7 days for postpartum hemorrhage. Excessive bleeding from uterus may necessitate hysterectomy. The mother may be given Rhogam if she is Rh negative.
Acquired female infertility may be prevented through identified interventions:
- "Maintaining a healthy lifestyle." Excessive exercise, consumption of caffeine and alcohol, and smoking have all been associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruits and vegetables, and maintaining a normal weight, on the other hand, have been associated with better fertility prospects.
- "Treating or preventing existing diseases." Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted diseases will impair fertility; obtaining prompt treatment for sexually transmitted diseases reduces the likelihood that such infections will do significant damage. Regular physical examinations (including pap smears) help detect early signs of infections or abnormalities.
- "Not delaying parenthood." Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age 35. Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood.
- "Egg freezing." A woman can freeze her eggs preserve her fertility. By using egg freezing while in the peak reproductive years, a woman's oocytes are cryogenically frozen and ready for her use later in life, reducing her chances of female infertility.
Treatment may be delivery by caesarean section and abdominal hysterectomy if placenta accreta is diagnosed before birth. Oxytocin and antibiotics are used for post-surgical management. When there is partially separated placenta with focal accreta, best option is removal of placenta. If it is important to save the woman's uterus (for future pregnancies) then resection around the placenta may be successful. Conservative treatment can also be uterus sparing but may not be as successful and has a higher risk of complications.
Techniques include:
- Leaving the placenta in the uterus and curettage of uterus. Methotrexate has been used in this case.
- Intrauterine balloon catheterisation to compress blood vessels
- Embolisation of pelvic vessels
- Internal iliac artery ligation
- Bilateral uterine artery ligation
In cases where there is invasion of placental tissue and blood vessels into the bladder, it is treated in similar manner to abdominal pregnancy and manual placental removal is avoided. However, this may eventually need hysterectomy and/or partial cystectomy.
If the patient decides to proceed with a vaginal delivery, blood products for transfusion and an anesthesiologist are kept ready at delivery.
Treatment is always necessary.
The treatment for hydatidiform mole consists of the evacuation of pregnancy. Evacuation will lead to the relief of symptoms, and also prevent later complications. Suction curettage is the preferred method of evacuation. Hysterectomy is an alternative if no further pregnancies are wished for by the female patient. Hydatidiform mole also has successfully been treated with systemic (intravenous) methotrexate.
The treatment for invasive mole or choriocarcinoma generally is the same. Both are usually treated with chemotherapy. Methotrexate and dactinomycin are among the chemotherapy drugs used in GTD. Only a few women with GTD suffer from poor prognosis metastatic gestational trophoblastic disease. Their treatment usually includes chemotherapy. Radiotherapy can also be given to places where the cancer has spread, e.g. the brain.
Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. These women also are likely to have an earlier menopause. It has been estimated by the Royal College of Obstetricians and Gynaecologists that the age at menopause for women who receive single agent chemotherapy is advanced by 1 year, and by 3 years for women who receive multi agent chemotherapy.
Pregnancy over age 50 has, over recent years, become more possible for women, due to recent advances in assisted reproductive technology, in particular egg donation. Typically, a woman's fecundity ends with menopause, which by definition is 12 consecutive months without having had any menstrual flow at all. During perimenopause, the menstrual cycle and the periods become irregular and eventually stop altogether, but even when periods are still regular, the egg quality of women in their forties is lower than in younger women, making the likelihood of conceiving a healthy baby also reduced, particularly after age 42. It is important to note, that the female biological clock can vary greatly from woman to woman. A woman's individual level of fertility can be tested through a variety of methods.
Men also experience a decline in fertility as they age, for example, the average time to pregnancy if a man is under 25 is just over 4.5 months but nearly two years if a man is over 40 (if the woman is under 25). The risk of genetic defects is greatly increased due to the paternal age effect. Children with fathers aged 40 or older are more than five times as likely to have an autism spectrum disorder than children fathered by men aged under 30. Researchers estimate that compared to a male fathering a child in his early 20's - there is double the chance of the child getting schizophrenia when the father is age 40, and triple the risk of schizophrenia when the father is age 50 (though, for most people this means the risk goes from approximately 1 in 121 when a man is 29, to 1 in 47 when a man is age 50 to 54). Men's fertility declines throughout the lifespan, with the volume of a man’s semen and sperm motility (the ability of sperm to move towards an egg) decrease continually between the ages of 20 and 80. The risk of dwarfism and miscarriage also increases as men age
In the United States, between 1997 and 1999, 539 births were reported among mothers over age 50 (four per 100,000 births), with 194 being over 55.
The oldest mother to date to conceive, was 71 years, and the youngest mother, 5 years old. According to statistics from the Human Fertilisation and Embryology Authority, in the UK more than 20 babies are born to women over age 50 per year through in-vitro fertilization with the use of donor oocytes (eggs).
Maria del Carmen Bousada de Lara is the oldest verified mother; she was aged 66 years 358 days when she gave birth to twins; she was 130 days older than Adriana Iliescu, who gave birth in 2005 to a baby girl. In both cases the children were conceived through IVF with donor eggs. The oldest verified mother to conceive naturally (listed currently in the Guinness Records) is Dawn Brooke (UK); she conceived a son at the age of 59 years in 1997 while taking oestrogen.
The goal of antiretroviral use during pregnancy is to reduce the risk of transmission of HIV from mother to child. It is important to choose medications that are safe for the mother and the fetus and which are effective at decreasing the total viral load. Some studies have shown an increase in stillbirths, preterm delivery, and delayed fetal growth in women using high doses of antiretroviral drugs during pregnancy. However, the overall benefits of ART are believed to outweigh the risks and all women are encouraged to use ART for the duration of their pregnancy.
Due to physiological changes in the body during pregnancy, it may be necessary to alter the dosing of medications so that they remain effective. Generally, the dose or the frequency of dosing are increased to account for these changes.
The recommended ART regimen for HIV-positive pregnant women consists of drugs from 4 different classes of medications listed below. In the United States, the favored regimen is a three-drug regimen where the first two drugs are NRTIs and the third is either a protease inhibitor, an integrase inhibitor, or an NNRTI.
- Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the "backbone" of ART and 2 medications are generally used in combination. Due to its known safety profile and extensive use in pregnant patients, zidovudine-lamivudine (ZDV/3TC) is the preferred choice as the NRTI backbone. Zidovudine may worsen anemia, so patients with anemia are advised to use an alternative agent. For women who are coinfected with Hepatitis B, tenofovir with either emtricitabine or lamivudine is the preferred NRTI backbone. NRTI use may cause lactic acidosis in some women, so it is important to monitor patients for this complication. Deaths from lactic acidosis and liver failure have been associated with the use of two NRTIs, stavudine and didanosine (Zerit and Videx, respectively); therefore, combinations involving these drugs should be avoided in pregnancy.
- Protease inhibitors (PIs) have been studied extensively in pregnancy and are therefore the preferred third drug in the regimen. Atazanavir-ritonavir and darunavir-ritonavir are two of the most common PIs used during pregnancy. There is conflicting data regarding their association with preterm births, so women who are at a high risk for premature delivery are advised not to use PIs. Some PIs have been associated with hyperglycemia but is unclear whether they add to the risk of developing gestational diabetes. Some PIs have been noted to cause hyperbilirubinemia and nausea, so these side effects should be monitored for closely.
- Integrase inhibitors (IIs) are generally the third drug in the regimen when a PI cannot be used. They rapidly reduce the viral load and for this reason, they are often used in women who are diagnosed with HIV late in the pregnancy. Raltegravir is the most common II used.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs), the most popular being efavirenz and nevirapine, may be used during pregnancy. However, there are significant toxicities associated with their use, making them a less desirable option.
- Efavirenz (brand name Sustiva, and a component of the combination drug Atripla) is classified as a category D drug by the US Food and Drug Administration indicating there are risks associated with its use during pregnancy. In a study analyzing the use of the drug in pregnant women, 2.3% of births were associated with birth defects. However, a systematic review of the safety of efavirenz use in humans during the first trimester found no increase in birth defects among women using the drug. Given the uncertain potential for risk the U.S. DHHS recommends against using efavirenz in the first trimester of pregnancy or in women who may become pregnant. They instead recommend a protease inhibitor based regimen with lopinavir or atazanavir. However, to simplify regimens and provide a uniform recommendation for HIV-infected individuals during pregnancy, the WHO continues to recommend efavirenz as a first line agent for HIV positive women. Women using efavirenz prior to their pregnancy may continue with the drug as it is more dangerous to stop or change medications during pregnancy because this can result in improper control of the viral load.
- Nevirapine (trade name Viramune) increases the risk of very serious liver damage in women with CD4 counts greater than 250 cells/mm . It is generally avoided in pregnant women. Women taking nevirapine safely prior to pregnancy may continue with the medication because nevirapine-related liver damage has not been seen in women previously using the medication.
The World Health Organization recommends that women with severe hypertension during pregnancy should receive treatment with anti-hypertensive agents. Severe hypertension is generally considered systolic BP of at least 160 or diastolic BP of at least 110. Evidence does not support the use of one anti-hypertensive over another. The choice of which agent to use should be based on the prescribing clinician's experience with a particular agent, its cost, and its availability. Diuretics are not recommended for prevention of preeclampsia and its complications. Labetolol, Hydralazine and Nifedipine are commonly used antihypertensive agents for hypertension in pregnancy. ACE inhibitors and angiotensin receptor blockers are contraindicated as they affect fetal development.
The goal of treatment of severe hypertension in pregnancy is to prevent cardiovascular, kidney, and cerebrovascular complications. The target blood pressure has been proposed to be 140–160 mmHg systolic and 90–105 mmHg diastolic, although values are variable.
The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.
In the vast majority of patients, treatment of PTD consist of chemotherapy. Only about 10% of patients with PTD can be treated successfully with a second curettage.