Benefit of vaginal sildenafil citrate in assisted reproduction therapy

Causes of female factorinfertility o Ovulation disorders (40%) o Aging o Diminished ovarian reserve (DOR) o Polycystic ovary syndrome (PCOS) o Premature ovarian failure o Others Thin endometrium o Adequatethickness of the endometrium is essential to accomplish a successful pregnancy in ART cycles o ‘‘Thin endometrium” defined as an endometrium thickness that can’t reach the threshold for embryo implantation.

• Sildenafil citrate can be prescribed off-label for female sexual dysfunction.
• Consult a doctor before using sildenafil citrate tablets for women.
• Side effects in women may include headache, flushing, or nasal congestion.
• Sildenafil works by increasing blood flow to enhance female arousal.
• Dosage for women varies; always follow medical advice.
• Sildenafil tablets may interact with other medications, like nitrates.
• Not approved by FDA specifically for female sexual dysfunction.
• Use with caution in women with heart conditions or high blood pressure.
• Possible benefits include improved libido and vaginal blood flow.
• Sildenafil should be taken on an empty stomach for best results.
• Long-term safety of sildenafil in women is not well established.
• Store sildenafil citrate tablets in a cool, dry place out of children’s reach.

Thin endometrium o Studiessuggest minimal endometrial thickness of 7 mm, (and preferably > 9 mm) to maximize pregnancy rates o Several reports have shown correlation between a ‘‘thin endometrium’’ and low implantation rates o Clinical pregnancy rates increased gradually from 53% among patients with a lining <9 mm, to 77% among patients with a lining of >16 mm. o Furthermore, thin endometrium causes higher risk of miscarriage Human Fertility 2009;12:198–203.

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If you take sildenafil for pulmonary arterial hypertension, do not take Viagra®, Vibrique™ or other PDE5 inhibitors, including tadalafil (Cialis®) or vardenafil (Levitra®). If you take too much sildenafil or take it together with these medicines, the chance for side effects will be higher. It is important to tell your doctor about any heart problems you have now or may have had in the past. This medicine can cause serious side effects in patients with heart problems. If you experience a prolonged or painful erection for 4 hours or more, contact your doctor immediately.

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This condition may require prompt medical treatment to prevent serious and permanent damage to your penis. If you experience a sudden loss of vision in one or both eyes, contact your doctor immediately. Check with your doctor right away if you have a sudden decrease in hearing or loss of hearing, which may be accompanied by dizziness and ringing in the ears. If you already use medicine for high blood pressure (hypertension), sildenafil could make your blood pressure go too low. Call your doctor right away if you have blurred vision, confusion, dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly, sweating, or unusual tiredness or weakness. Understanding the endometrium Endometrium hastwo layers: o a basalis layer that is adherent to the myometrium o and a functional layer which undergoes different phases during a menstrual cycle o This lining is under the control of estrogen hormone and passes through different phases during the monthly menstrual cycle of female.

Understanding the endometrium o Theaverage thickness of endometrium is 8 mm which increases further in pregnancy.

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This medicine does not protect you against sexually transmitted diseases (including HIV or AIDS). Use protective measures and ask your doctor if you have any questions about this. Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements. Along with its needed effects, a medicine may cause some unwanted effects.

Sildenafil may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

Although not all of these side effects may occur, if they do occur they may need medical attention. Check with your doctor immediately if any of the following side effects occur: burning feeling in the chest or stomach burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings decrease in amount of urine or the frequency of urination dizziness or lightheadedness, especially when getting up suddenly from a lying or sitting position dryness, redness, scaling, or peeling of the skin increase in the size of the pupil redness, burning, or swelling of the eyes redness, itching, or tearing of the eyes seeing shades of colors differently than before swelling of the face, hands, feet, or lower legs unusual feeling of burning or stinging of the skin Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them: pain or tenderness around the eyes and cheekbones diarrhea or stomach cramps (severe or continuing) numbness or tingling of the hands, legs, or feet redness, soreness, swelling, or bleeding of the gums sensation of motion, usually whirling, either of one's self or of one's surroundings sexual problems in men (continuing), including failure to experience a sexual orgasm sores in the mouth and on the lips Other side effects not listed may also occur in some patients. Less than 8 mm is considered inadequate o During pregnancy, at least 9 mm of thickness is required to provide a site for proper implantation of fetus.

Mechanism of action

Ask your healthcare professional how you should dispose of any medicine you do not use. Store mixed oral liquid in the refrigerator. Throw away any unused mixed Revatio® oral liquid after 60 days. It is important that you tell all of your doctors that you take sildenafil. If you need emergency medical care for a heart problem, it is important that your doctor knows when you last took sildenafil.

Inclusion Criteria

Do not use this medicine if you are also using a nitrate medicine, often used to treat angina or high blood pressure. Some illegal ("street") drugs called "poppers" (such as amyl nitrate, butyl nitrate, or nitrite). Do not use this medicine if you also use riociguat (Adempas®). If you will be taking this medicine for pulmonary arterial hypertension, your doctor will want to check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. o This thickness not only plays a vital role in the implantation of fetus to the walls of the uterus but also supports the growing baby in the later stages of pregnancy.

What other drugs will affect sildenafil?

If you notice any other effects, check with your healthcare professional. You may report side effects to the FDA at 1-800-FDA-1088. Contents o Overview offemale reproductive system o Infertility o Thin endometrium o Sildenafil o Indications, dose and dosage o Clinical studies o Summary and conclusion Female reproductive system ▪The femalereproductive system is made up of the internal and external sex organs that function in human reproduction. ▪The internal sex organs are the uterus and Fallopian tubes, and the ovaries. ▪The external sex organs are also known as the genitals and these are the organs of the vulva including the labia, clitoris and vaginal opening.

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Female internal sex organs Uterus oThe uterus is a hollow, muscular, pear-shaped organ. o Connected to the two fallopian tubes on its superior end and to the vagina (via the cervix) on its inferior end. o The inner lining of the uterus, known as the endometrium, provides support to the embryo during early development. o The sildenafil pfizer 100g visceral muscles of the uterus contract during childbirth to push the fetus through the birth canal. Female internal sex organs Fallopiantubes o The fallopian tubes are a pair of muscular tubes that extend from the left and right superior corners of the uterus to the edge of the ovaries. Consequence of thin endometrium oIf, due to any cause, this lining becomes thin, it becomes impossible for the fertilized egg to get implanted to the wall.

• Sildenafil may improve blood flow to the clitoris, aiding arousal.
• Use caution with grapefruit or grapefruit juice, which can affect drug levels.
• Document any pre-existing medical conditions before starting sildenafil.
• Sildenafil may cause dizziness; avoid activities requiring alertness.
• Women with liver or kidney impairment should consult a physician first.
• The drug is not a hormone; it works on blood vessels.
• Patients should report any sustained erections or discomfort.
• Combining sildenafil with certain antidepressants may alter effectiveness.
• Keep track of any changes in sexual satisfaction or function.
• Sildenafil should be used as part of a comprehensive treatment plan.
• Avoid using sildenafil with recreational drugs that affect the cardiovascular system.
• Always follow up with your healthcare provider for ongoing assessment.

o This can lead to infertility of a female uterus and pregnancy cannot take place because a fertilized egg needs a strong support for implantation and support for growing into an embryo.

Medical uses

o The process by which the egg cell (ovum) is released is called ovulation. o The speed of ovulation is periodic and impacts directly to the length of a menstrual cycle. Ovulation, conception & implantation oOvulation is the release of egg from the ovaries. o Conception/ Fertilization is the union of a human egg and sperm, usually occurring in the ampulla of the fallopian tube. o Implantation is the very early stage of pregnancy at which the conceptus (fertilized embryo) adheres to the wall of the uterus. Causes of thin endometriallining Thinning of endometrial lining is a serious problem from gynecological point of view.

• Sildenafil citrate is a phosphodiesterase type 5 inhibitor.
• It may help women with sexual arousal disorder by increasing blood flow.
• Discuss mental health factors affecting libido with a healthcare specialist.
• Be aware of possible nasal congestion after taking sildenafil.
• Avoid using expired medication, as effectiveness may diminish.
• The effectiveness varies among women; results are individual.
• Use sildenafil responsibly to minimize potential adverse effects.
• Women should inform providers of all medications taken regularly.
• Sildenafil is not a cure for sexual dysfunction, only a symptomatic aid.
• Adequate sexual education can improve understanding and expectations.
• Proper dosage and timing are important for safety and efficacy.
• Sex therapy or counseling may complement medication use effectively.

Poor health of endometrial tissue (Any injury, surgery, trauma or infection can cause damage to the endometrial lining) 4.

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Implantation o At thisstage of prenatal development, the conceptus is a blastocyst. o It is by this adhesion that the fetus receives oxygen and nutrients from the mother to be able to grow. o Implantation of a fertilized ovum is most likely to occur about 9 days after ovulation, ranging between 6 and 12 days. “ Infertility a diseaseof the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse Infertility o Global incidenceof infertility is about 13- 18% o The incidence of infertility steadily increases in women after age 30. o In India, although population growth is a major concern, there are a substantial number of infertile couples. Long term use of birth control pills 5.

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o The fallopian tubes end in a funnel-shaped structure called the infundibulum, which is covered with small finger-like projections called fimbriae. o The fimbriae pick up released ova from ovary and carry them into the infundibulum for transport to the uterus. o The inside of each fallopian tube is covered in cilia that work with the smooth muscle of the tube to carry the ovum to the uterus. Female internal sex organs Ovaries oThe ovaries are small, paired organs located near the lateral walls of the pelvic cavity. o These organs are responsible for the production of the egg cells (ova) and the secretion of hormones. Signs and symptoms ofthin endometrial lining There are no specific signs and symptoms related to the thin endometrial lining.

• Sildenafil citrate tablets are typically taken 30-60 minutes before intimacy.
• Monitoring by a healthcare professional is recommended for women.
• Use sildenafil cautiously if you have a history of stroke or heart attack.
• Combining sildenafil with other ED medications is dangerous.
• Pregnancy and breastfeeding considerations should be discussed with a doctor.
• Sildenafil does not induce arousal but enhances physiological responses.
• Not suitable for women with or at risk of abnormal heart rhythms.
• Potential for psychological as well as physical benefits exists.
• Ensure trusted pharmacy sources when purchasing sildenafil for women.
• Sildenafil is available in various dosages, such as 25 mg, 50 mg, 100 mg.
• Discontinue use if adverse effects like chest pain occur.
• A comprehensive sexual health evaluation can determine if sildenafil is appropriate.

However females suffering from thin endometrial lining may present with: 1. Sildenafil ▪Sildenafil is aselective inhibitor of Phosphodiesterase -5 (PDE-5), which is cGMP- specific and responsible for the degradation of cGMP ▪Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) Background The endometrium isthe special epithelial lining of the uterine cavity It has two layers: A superficial functional layer and a deeper basal layer The endometrial growth is reliant on the uterine blood flow Uterine blood flow is closely related with the vascular development of endometrium plays a significant role in the development of a dominant follicle, formation of a corpus luteum, and growth of endometrium This is essential to support endometrial growth after menstruation and to provide a vascularized receptive endometrium for implantation “ In caseswhere ‘‘thin’’ endometrium results from reduced endometrial blood flow, the use of vasoactive substances may increase endometrial perfusion with a consequent improvement in endometrial growth.