By F. Milten. Fort Hays State University. 2018.
When the semen is a bit less If you do not have HSG facilities but you have/ than the WHO criteria it does not mean that this is are a good ultrasonographer cialis extra dosage 60mg low price, try to visualize the the direct cause of subfertility – as already men- tubes and check their patency by using normal tioned generic cialis extra dosage 200mg mastercard, the quality of semen fluctuates a lot and saline: insert a small intrauterine cannula or catheter many times more than one factor makes a couple and slowly rinse the catheter with maximum 50ml subfertile! You should only • Uterine cavity do this method under aseptic conditions, and one • Tubes night before and 1h before the procedure you • Adhesions should administer 200mg doxycycline and 50– 100mg diclofenac. Both HSG and hydrotubation Disadvantages of HSG are that it often gives false- are reported to be successful in achieving pregnan- negative or false-positive results and it needs some cies in selective patients: thin peritubal adhesions specialized X-ray equipment that might not be 11 might be opened (level of evidence 3). In addition it should be noted that the X-ray contrast solution is rather expensive. Schistosomiasis and infections To prevent infections and reduce pain: one night before and 1h before HSG give 200mg In some areas in the world schistosomiasis could be doxycycline and 50–100 mg diclofenac. Detect schistosomiasis in urine dure is as follows: on the X-ray table you do a or cervix biopsy (see Chapter 9) and if positive, speculum examination and grab the cervix with a give appropriate treatment. Clean the cervix with antiseptic and If you suspect gonorrhea or a Trichomonas infec- introduce a hysterophore or a small catheter. The tion: do a high vaginal swab to exclude pathogenic big advantage if you have a hysterophore is that microorganisms and treat accordingly (see Chapter this instrument will close the cervix and no fluid 17 about STI). After the In some countries tuberculosis is endemic and instrument has passed the internal cervix, attach the causes infertility. It is very difficult to detect 176 Subfertility endometrial tuberculosis. This could be done after Table 3 Overview of possible treatments for various endometrium sampling using the smallest cannula infertility disorders; conditions in bold cannot be treated from manual vacuum aspiration and special patho- In woman logy staining. No ovulation PCOS: ovulation induction with clomiphene citrate DIAGNOSIS OF SUBFERTILITY Hyperprolactinemia: bromocriptine Early menopause After you have done the history taking and specific Hypophysis abnormalities examination you can diagnose the cause of the Tubes are not patent subfertility. Hydrosalpinx: refer for surgery or IVF Some causes you can treat others not. It is always Adhesions: refer for surgery or IVF important if you are a health provider to give Proximal tube blockage: refer for IVF support to your patients: give a clear explanation of Endometriosis: sometimes surgery COC or Depo- the cause of the disease and in the meanwhile also Provera (see Chapter 6) give an opportunity for the patients to show their Cervical hostility: IUI concern and their emotions. For many men and In man women the inability to procreate gives considerable Semen not good enough grief and stress, not only to themselves but also to Azoospermia their social environment. If you address these issues Oligospermia: IUI you could help your patients cope with their diffi- Unexplained cult situation. Superovulation and IUI or refer IVF TREATMENT OF SUBFERTILITY IN LOW- IVF, in vitro fertilization; COC, combined oral contracep- INCOME COUNTRIES tion; IUI, intrauterine insemination Some of the subfertility treatment is possible on dis- trict or regional level in most low-income coun- tries. Some of the infertility treatment like IVF is Flowchart for subfertility only possible on a national level because it is expen- The flow chart in Figure 9 is a good tool to use in sive and needs more expertise. In this book we will decision-making in infertility patients. Please copy only talk about the treatment you could provide the card and put it on the wall. In the flowchart with district and regional level facilities. Table 3 you see that the first decision is based on the regu- gives an overview of the conditions you could treat; larity of the cycle. Women with a regular cycle the conditions you cannot treat are shown in bold. Women with an irregular cycle should treatment clinic is dependent on the situation in first have had ovulations for at least 6 months, be- your health facility – the magnitude of the sub- fore you perform a HSG. But now you have ovary syndrome the knowledge about subfertility, you could start with treatment of the ‘easy’ causes of subfertility – When the woman is severely overweight, she first anovulation because of PCOS and because of should lose weight. More difficult treatment such ovulating again when they lose about 10–20% of as intrauterine insemination (IUI) and surgery you their weight. In order to reach this weight loss, can always add later when you have acquired the patients should combine a low-calorie diet with skills and when the need is there! Make a plan with your patient: give her a usually once people know that your clinic is provid- low sugar, low alcohol and low-fat diet and let her ing any kind of treatment for subfertility, many will exercise 1h per day. Weigh her monthly to moni- come, as subfertility is a big problem almost every- tor progress. Give 1 tablet CC 177 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS Cycle length 23–35 days > 35 days PCT and US Galactorrhea No galactorrhea on CD 12–13 If PCT and US both Bromocriptine Clomiphene citrate normal: do HSG 2. PCT, post-coital test; US, ultrasound; CD, cycle day; HSG, hysterosalpingography 50mg on cycle day 3–7 (again: day 1 is the day the When no follicles are growing when using 1 tablet period starts, the woman has to use only five pills CC 50 mg on day 3–7, next cycle give her 2 tablets per month, and she should not wait until menstrual CC 50mg on cycle day 3–7. When no follicles are flow stops before taking them). You must monitor growing on 2 tablets: next cycle prescribe 3 tablets multiple follicle growth (twins, triplets etc. This is the maximum ultrasound during the first cycle: CC can give dose. If still no ovulation occurs, start with con- multiple follicles and so multiple pregnancies! If advise the couple to have only protected inter- still no follicle forms, you could refer your patient course (condoms) this cycle. When first ovulatory cycle: CC induces cervical hostility too many follicles are growing: start the next cycle in some patients! You can time the PCT and ovula- with half a tablet of CC 50mg on cycle day 3–7. Wash the sperm – you could do this in very when they are 20mm. When you give CC, they expensive fluid, but it is also possible to use the can grow a bit bigger and ovulation can be a few serum of the woman. So instruct your patients to have inter- men [produced <1h previously in a sterile (boiled) course every second day during the second half of container via masturbation].
The results are conflicting later pregnancy discount cialis extra dosage 40 mg line, thrombosis of the uteroplacental and understandably biased with difficulties in con- vasculature34–36 cialis extra dosage 200mg sale. Live birth rate in pregnancies with trolling for confounding factors and inaccuracy in no pharmacological intervention has been reported quantifying the dose of exposure. The a balanced reciprocal or Robertsonian transloca- malformation ranges from the mildest form with tion13,38,39 (Figure 1). Carriers of balanced transloca- slight indentation at the fundus (arcuate uterus) to tion are usually phenotypically normal and unaware the most extreme form with complete duplication of the condition. However, up to 70% of their (uterus didelphys) (Figure 2). This leads to alies in both the general population and women with a much higher risk of miscarriage, or rarely result- recurrent miscarriages is not clear. Wide variation of ing in live birth with multiple congenital malfor- prevalence from 1. A retrospective review of reproductive performance in patients with untreated uterine The risk of miscarriage resulting from chromo- anomalies suggested that these women have high somal abnormality increases with maternal age. In rates of miscarriage and preterm delivery, resulting in couples with recurrent miscarriage, chromosomal 42 a term delivery rate of only 50%. However, with increasing Cervical incompetence number of miscarriages, the risk of euploid preg- nancy loss increases, suggesting some other under- Cervical incompetence is defined as the inability lying pathology accounting for the loss. Reprinted with permission of Dr Jonathan Wolfe, Department of Biology, Galton Laboratory, University College London, UK 136 Recurrent Miscarriage including Cervical Incompetence Figure 2 The American Society for Reproductive Medicine classification of Müllerian anomalies. Copyright 2012 by the American Society for Reproductive Medicine. No part of this presentation may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording or by any informa- tion storage and retrieval system without permission in writing from the American Society for Reproductive Medicine, 1209 Montgomery Highway, Birmingham, AL 35216. It is a well-recognized cause pact on pregnancy outcomes, whereas subserosal of late miscarriage but the true incidence is un- lesions do not46–51. Epidemiological studies suggest an approxi- fibroids is more controversial. The result from uterine trauma after vigorous intra- cervix is the main mechanical barrier separating the uterine curettage or intrauterine infection. This has pregnancy from the vaginal bacterial flora. Many been implicated in recurrent miscarriage presum- patients who have asymptomatic mid-trimester ably due to the reduced uterine cavity volume as cervical dilation also have evidence of subclinical 44 well as fibrosis and inflammation of the endo- intrauterine infection. It is unclear whether this metrium leading to defective implantation and high rate of microbial invasion is the result or the pregnancy loss. Dilatation and curettage (D&C) cause of premature cervical dilation. Uterine fibroids have long been associated with a variety of reproductive problems, including preg- Endocrine factors nancy loss. Presumed mechanisms include mechani- Systemic endocrine factors cal distortion of the uterine cavity, abnormal vascularization, abnormal endometrial develop- Diabetes and thyroid disease have been associated ment, endometrial inflammation, abnormal endo- with sporadic miscarriage but there is no direct crine milieu and structural and contractile evidence that they contribute to recurrent mis- myometrial abnormalities45, any or all of which carriage. Women with well-controlled diabetes may impede embryonic implantation. It is well mellitus and treated thyroid dysfunction do not 137 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS carry higher risks for recurrent miscarriage52,53. The Empirical use of antibiotics in pregnancy should prevalence of diabetes and thyroid dysfunction in be avoided due to lack of evidence of benefit and women with recurrent miscarriage is similar to that potential harm with increased risk of cerebral reported in the general population54,55. Luteal phase defect and progesterone deficiency Inherited thrombophilic defects A functional corpus luteum is essential for the im- The hemostatic system plays a crucial role in both plantation and maintenance of early pregnancy, the establishment and the maintenance of preg- primarily through the production of progesterone, nancy. The fibrinolytic pathways are involved in which is responsible for the conversion of pro- the implantation and are important in maintaining liferative to a secretory endometrium suitable for an intact placental circulation. Luteal phase defect, in thrombophilic defects on recurrent miscarriage and which insufficient progesterone production results later pregnancy complications are presumably in retarded endometrial development, has long caused by an exaggerated hemostatic response dur- been believed to be associated with recurrent mis- ing pregnancy, leading to thrombosis of the utero- carriage. However, there are no accurate and reli- placental vasculature and subsequent fetal demise. Commonly screened infections including PROGNOSIS FOR HEALTHY PREGNANCY toxoplasmosis, rubella, cytomegalovirus, herpes AFTER RECURRENT MISCARRIAGE and Listeria infections do not fulfill these criteria and routine screening for these disorders is not The prognosis for healthy pregnancy after mis- recommended57. Currently, there are no available carriages depends on: data to suggest an association between tuberculosis • Age or AIDS with recurrent miscarriage. Table 2 Established causes of systemic thrombosis associated with obstetric morbidity Recurrent first-trimester Recurrent loss Recurrent late loss Non-recurrent late loss loss before 25 weeks >22 weeks >19 weeks FVL OR 2. OR, odds ratio; CI, confidence interval; FVL, factor V Leiden; APCR, activated protein C resistance; PGM, prothrombin gene mutation; MTHF mutation, methylene tetrahydrofolate reductase mutation; AT III def. Speculum examination A descriptive cohort study in Denmark has shown Look for signs of infection and take a wet mount that for women aged 30–34 years with a history of and genital swab for culture if a cerclage seems three first-trimester miscarriages, 66. There was a significantly decreased chance of live birth with increasing maternal age and increasing number of miscarriages at presentation59. Recommended investigations Of the many risk factors, parental karyotype abnor- malities, APS, APCR and cervical incompetence are the MANAGEMENT OF COUPLES WITH only established causes of recurrent miscarriage. RECURRENT FIRST- AND SECOND- Limited resources should be directed in identifying TRIMESTER MISCARRIAGE these. Taking into consideration the immense History taking suffering of couples with recurrent miscarriage and the significant amount of money spent on tradi- A thorough history of the patient is very important. Please above-mentioned investigations might be well see Chapter 1 on how to take a basic gynecological accepted by the patients and be more cost-effective.
Of interest is the effect of NRTIs on the occurrence of myocardial infarction discount 100mg cialis extra dosage mastercard. The D:A:D study reported an increased rate of MI for abacavir and ddI (Sabin 2008) buy cheap cialis extra dosage 50mg on line. An elevated incidence of cardiovascular events was also found in a retrospective analysis of the SMART study as well as in another retrospective analysis of a Danish work- group (Obel 2010). Inflammation may be the cause of this increased cardiovascular event rate (Lundgren 2008b). On the contrary, a recent FDA meta-analysis plotting data of almost 10,000 patients could not find a statistically significant difference of MI events between subjects receiving abacavir-containing ART and other ART regimens (Ding 2011). When using PIs, the increased event rate was associated with classical risk factors such as diabetes and hyperlipidemia which may explain some of the events. Patients undergoing therapy with abacavir also were likely to be male and had an increased rate of risk factors like increased age, diabetes and pre-exist- ing cardiovascular disease. Further investigation is needed to clarify how much classical risk factors contribute to the MI event rate. When looking at NNRTIs and some PIs (nelfinavir, saquinavir) and NRTIs (AZT, d4T, 3TC, tenofovir) there was no hint of an increased cardiovascular event rate (Worm 2010). To what extent these results have an effect on medical care of HIV-infected patients remains unclear. However, the SMART study did show an increase in the cardiovascular event rate in patients in whom ART was discontinued intermittently compared to patients who received ART continuously (El-Sadr 2006). It was suggested that increased inflam- mation during treatment interruption is responsible for this (Kuller 2008). Summing up, the evidence for negative effects of ART on CAD is not strong enough to influence the decision of when to start or switch ART regimens in terms of the cardiovascular risks. HIV+ men exhibited slightly more positive arterial remodel- ing on coronary CT than negative controls (Miller 2015). Also, the prevalence of coronary calcium is higher (Chow 2015). However, in a sonographic controlled study of the development of carotid plaques HIV+ patients with high baseline CD4 T cells did not have an increased risk compared to normal controls. It was concluded that the degree of immunodeficiency might play a role in the progression of atheroscle- rosis. Studies focusing on subclinical atherosclerosis predict an increasing prevalence of CAD in the near future as the population continues to age (Triant 2009, Lo 2010). It has been shown that HIV+ subjects exhibit a marked cardiovascular risk profile (Neumann 2003+2004a+b). Most notably, cigarette consumption is two- to three- fold higher than in non-infected populations. In addition, uncontrolled blood pressure is frequent in HIV+ patients (Nuernberg 2015) and a recent publication revealed that treatment of risk factors is frequently insufficient (Reinsch 2012). Especially patients with known CAD and diabetes exhibit a high risk for subsequent cardiovascular events (CAD: 7. Prevention and treatment of CAD Prevention and early diagnosis of CAD in patients older than 45 years and with an elevated cardiovascular risk profile should, therefore, be routine in current thera- peutic management of HIV infection. Primary and secondary prevention should aim at modifying known risk factors (Lundgren 2008a). Prevention of CAD is based on the most recent general guidelines (Smith 2006, Perk 2012) (Table 1) and EACS guide- lines (Lundgren 2008a). A number of different scores for calculation of the cardio- vascular risk profile is proposed. However, all of them take into account the classi- cal risk factors hyperlipidemia, diabetes, hypertension and smoking. Primary prevention of CAD aims at the control of these risk factors to lower the future risk of cardiovascular events. Primary prevention of CAD starts by modifying lifestyle and comprises cessation of smoking and a balanced diet with a low content of saturated fatty acids and trans- unsaturated fatty acids, a reduced salt intake as well as a high amount of fibers, fruits and vegetables. Moderate intensity physical activity with a cumulative duration of 2. Weight reduction which aims at a BMI of 20–25 is beneficial for the control of blood pressure and metabolic imbalance. If control of blood pressure cannot be achieved with lifestyle modifications only, drug therapy should be initiated. Drug therapy can comprise any of the standard antihypertensives (diuretics, ß blockers, calcium channel blockers, ACE inhibitors angiotensin receptor blockers and renin antagonists) or a combination (caveat: do not combine ACE inhibitors, angiotensin receptor blockers and renin antagonists). When using calcium channel blockers, interactions with ART (boosted PIs! When multiple metabolic risk factors are present, diuretics and ß blockers are not recommended. The aim of blood pressure control should be a sys- tolic blood pressure <140 mmHg and a diastolic blood pressure <90 mmHg. Hyperlipidemia can be approached with lipid lowering drugs. Statins are the therapy of first choice but might interact with ARVs. In particular, several PIs act as substrates for isoenzyme 3A4, a subgroup of the cytochrome p450 system. Inhibition of the isoenzyme 3A4 can increase the blood concentration of statins and induce side effects. In contrast to most other statins, pravastatin and fluvastatin are not modu- lated by isoenzyme 3A4. Therefore, these two drugs are preferred in HIV+ patients.
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