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Journal für Reproduktionsmedizin und Endokrinologie – Journal of Reproductive and –

Andrologie • Embryologie & Biologie • Endokrinologie • Ethik & Recht • Genetik Gynäkologie • Kontrazeption • Psychosomatik • Reproduktionsmedizin • Urologie

First Steps into Gynaecological Endocrinology and in Resource-poor Countries: An Eritrean Experience Gnoth C, Kaulhausen H, Marzolf S J. Reproduktionsmed. Endokrinol 2013; 10 (1), 44-48

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Indexed in EMBASE/Excerpta Medica/Scopus Krause & Pachernegg GmbH, Verlag für Medizin und Wirtschaft, A-3003 Gablitz Treatment in Resource-poor Countries First Steps into Gynaecological Endocrinology and Reproductive Medicine in Resource-poor Countries: An Eritrean Experience

C. Gnoth1 , H. Kaulhausen2, S. Marzolf3

Background: Gynecological endocrinology and reproductive medicine within the systems of developing countries is underappreciated and methods to incorporate basic infertility workup and treatment needs to be addressed. However, most recommendations of how to proceed in particular, though, are very general. We exemplarily report our approach in Eritrea. Methods: Two one-week intensive training courses on gynecological endo- crinology and reproductive medicine (lectures and hands on training) were given 2011 and 2012 at the Orotta National Referral Maternity Hospital in Asmara, Eritrea. Important subjects included: education and training in contraception awareness, methods to optimize fertility potential, utilization of vaginal ultrasound for cycle monitoring, performance of hysterocontrastsonograhy, and one-step preparation for intrauterine inseminations. Results: After two intensive courses a basic infertility work up is possible with pelvic ultrasound assessment and contrastsonography for tubal patency. Simplified intrauterine inseminations after mild ovarian stimulation are possible as well and represent the first step into assisted . All procedures are feasible and performed independently by the trainees. Conclusions: Basic gynecological endocrinology and infertility care in resource-poor countries is possible. The Eritrean example of intensive courses with training in hysterocontrastsonography and one step intrauterine inseminations may encourage others to follow and introduce basic infertility care into other resource-poor countries. Key words: developing countries, infertility, , low-cost gynecological endocrinology and infertility treatment, simple infertility work up, Eritrea

Gynäkologische Endokrinologie und Reproduktionsmedizin in einem Entwicklungsland: Erste Erfahrungen am Beispiel Eritreas. Hinter- grund: Der unerfüllte Kinderwunsch in einem Entwicklungsland bedeutet für betroffene Frauen ein schweres Stigma mit sozialem Abstieg und gesell- schaftlicher Isolation. Ein dringender Handlungsbedarf wird heute auch von der WHO nicht mehr in Frage gestellt. Allerdings gibt es kaum Vorschläge zum Vorgehen in der Praxis. Wir berichten deshalb von unseren Erfahrungen in Eritrea. Methodik: Am Orotta National Referal-Hospital in Asmara, Eritrea, haben wir 2011 und 2012 jeweils einen Intensivkurs in Gynäkologischer Endokrinologie und Reproduktionsmedizin abgehalten und mit angehenden Fach- ärzten dort eine Sterilitätssprechstunde durchgeführt. Ergebnisse: Das Ursachenspektrum der Sub- und Infertilität in einem Entwicklungsland unterschei- det sich deutlich von dem in westlichen Ländern. Es handelt sich oft um junge Frauen mit entzündlichen Tubenschäden und Regeltempostörungen bzw. Männer mit den Folgen genitaler Infektionen. Dazu kommt ein kaum vorhandenes Wissen über den Zyklus oder die zyklusabhängige Fruchtbarkeit. In beiden Intensivkursen wurden deshalb die Gebiete natürliche Fertilität, Kontrazeption, Optimierung der natürlichen Fertilität und die Infektionsprophylaxe besonders berücksichtigt. Die Interpretation von Basaltemperaturkurven zur endokrinologischen Diagnostik erlaubt das Erkennen wichtiger Pathologien auch ohne endokrinologisches Labor. Die einfache Sterilitätsdiagnostik wird erweitert durch die standardisierte Durchführung von Postkoitaltests, der Nativmikroskopie des Ejakulates und durch die Durchführung von Hysterokontrastsonographien zur Abklärung des Tubenfaktors. Auch therapeutische Schritte konnten eingeführt werden. Clomifenstimulationen und Ovulationsinduktionen sind möglich. Wichtige Prozeduren sind die intrazervikale Insemi- nation (Nativsperma bei der häufigen Parvispermie) und intrauterine Inseminationen nach Aufbereitung des Spermas mit einem „Ready-to-use“-Einmalset. Ein andrologisches Labor ist nicht erforderlich. Schlussfolgerung: Das hier vorgestellte Beispiel soll Mut machen, auch in anderen sogenannten Entwick- lungsländern in gynäkologischer Endokrinologie und Reproduktionsmedizin auszubilden und erste Schritte einzuführen. J Reproduktionsmed Endo- krinol 2013; 10 (1): 44–8. Schlüsselwörter: Gynäkologische Endokrinologie, Reproduktionsmedizin, Entwicklungsland, natürliche Fertilität, Kontrazeption, intrauterine Inseminationen, Hysterokontrastsonographie

 Introduction because infertility is a hidden fate in tra- gratory work or military service. Spe- ditional societies of developing coun- cific reasons for the lack of diagnosis Gynecological endocrinology and infer- tries [2]. This hidden fate causes exten- and treatment in cases of infertility are tility treatment in resource-poor coun- sive economic consequences for the (1.) poor awareness and shame, (2.) un- tries is under appreciated within the glo- childless elderly couple whereby the availability of tools for diagnosis and bal agenda of reproductive health, yet lack of children leads to loss of financial treatment and (3.) the high-cost of inter- causes severe social and psychological and family supportive security. Impor- ventions [3]. suffering in affected couples. World- tant known causes of infertility in devel- wide, around 6 to 12% of couples are oping countries are male and female in- This hidden problem of infertility in de- faced with problems of subfertility. In fectious diseases (sexually transmitted, veloping societies has gained more and developing countries, population sur- unhygienic and prac- more scientific attention [3–6] and the veillance studies report a prevalence of tices, female genital mutilation), ovula- possibilities of western and infertility up to 25% [1]. These numbers, tion disorders due to malnutrition and its effectiveness have attracted attention though, must be interpreted cautiously long-term couple separation due to mi- also in the general population especially

Received: October 17, 2012; accepted after revision: January 30, 2013 From the 1Centre for Gynaecological Endocrinology and Reproductive Medicine (green-ivf) and Department of Obstetrics and , University of Cologne; the 2Hammer Forum, Hamm, and the 3Department of Global Health, University of Washington, USA Correspondence: PD Dr. Christian Gnoth, green-ivf, D-41515 Grevenbroich, Rheydter Straße 143, Germany; e-mail: [email protected]

44 J Reproduktionsmed Endokrinol 2013; 10 (1) For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. Infertility Treatment in Resource-poor Countries in countries with Internet access [7]. The Orotta National Referral Maternity Hos- obstetrics and gynaecology in front of an World Health Organization (WHO), im- pital in Asmara had an annual estimate international board in February 2012. portant scientific organizations of repro- of 10,600 outpatient visits in the outpa- ductive medicine, and non-governmen- tient department (OPD) and more than The subjects of the first course were in tal organizations (NGOs) are fortunately 9,000 deliveries p.a. The surgical perfor- detail: aware of this challenge to incorporate mance comprised about 1000 caesarean – basic facts on human fertility from infertility care into programs of family sections and about 200 major gynaecol- to [10] planning, motherhood care and repro- ogical per year. The clinical – reproductive health with special em- ductive health [8]; and, in addition, to and surgical work was done by six Ob/ phasis on infectious diseases (particu- adapt infertility care to local needs and Gyn senior consultants and the five Ob/ larly: obstetrical , tubercu- resources [9]. Within the literature, Gyn residents with support from mid- losis) and sexually transmitted dis- though, there is very limited information wives, nurses and anaesthetists. eases as to how to implement basic and cost – natural methods for effective infertility services in low re- Two ultrasound machines with an ab- (contraception [11–13] and fertility source settings. This article reports our dominal and vaginal scanner are avail- awareness [14, 15]) with particular encouraging experience with first steps able. Principally, hormonal assays for emphasis on interpretation of basal into infertility care in Eritrea. LH, FSH, estradiol, testosterone and body temperature charts for diagnos- are available but the capac- tic purposes The Orotta National Referral Maternity ity of performing hormonal analyses is – and men- Hospital in the capital city of Asmara has very limited. There is one phase contrast struation disorders (primary and sec- the largest national delivery ward in microscope in the general clinical labo- ondary amenorrhea, hyperandrogen- Eritrea with more than 9.000 deliveries ratory of the Orotta National Referral aemia) per year. Since 2003, the maternal mor- Hospital where native semen analysis – basics of modern contraception tality has decreased from 752 to 486 per can be performed. – diagnosis and treatment options of 100,000 live births in 2010. With the help of “Hammer Forum”, a German  Structured Intensive – basic pelvic ultrasound with particu- NGO (www.hammer-forum.de), a new lar emphasis on vaginal ultrasound maternity hospital was built and with the Courses of GRE and ART and hysterocontrastsonography using support and supervision of the Ministry The first intensive course for ultrasound contrast gel and foam or of Health, a postgraduate medical educa- (five residents in Ob/Gyn and six senior saline [16–18] tion program in obstetrics and gynaecol- Ob/Gyn consultants (general obstetri- – basic semen analysis and performing ogy was implemented in 2009 with the cians and gynaecologists)) was given in and interpretation of post-coital-tests first batch of Ob/Gyn specialists, edu- March 2011. It included 20 hours of lec- [19–23] cated and trained in Eritrea, graduating tures in the afternoon over one-week and – ART under circumstances of poor re- in 2012. The gaps in the Ob/Gyn resi- hands on training under supervision in sources from intrauterine insemina- dency curriculum were filled with tech- the outpatient department (OPD) in the tion to mini-ivf [24] nical, academic, and practical assistance morning. For the afternoon sessions on – basics of ovarian stimulation and by external visiting faculties from Ger- family-planning and reproductive health, cycle monitoring many, the Netherlands, the USA and medical students and midwives were in- Sudan. Early on, officials became aware vited to attend. In the OPD, the trainees were exposed to of the urgent necessity of including the relevant elements of infertility work gynaecological endocrinology and as- The content of the lectures followed the up and were trained using case demon- sisted reproductive techniques into the “Curriculum for Training strations and discussions. In addition, the curriculum and training of the residents. in Reproductive Medicine” by the Royal trainees were taught to counsel patients A huge demand for infertility diagnosis Collage of Obstetricians and Gynaecol- about the methods of taking their basal and treatment became obvious. There- ogists of 2007 (United Kingdom, http:// body temperature [25–27], recording and fore, the Hammer Forum was asked to www.rcog.org.uk/files/rcog-corp/up- interpreting cervical mucus symptoms start a pilot project of implementing loaded-files/ED-SUBSPEC-RM-Curri- which can be observed externally [28– basic infertility care. We set-up a program culum.pdf) and for teaching natural fer- 30]. Under supervision, the Ob/Gyn resi- of two intensive courses in gynaecol- tility regulation we based on own mate- dents deepened their technique of both ogical and reproductive endocrinology rial and media from the Institute for abdominal and transvaginal vaginal ultra- (GRE) and assisted reproductive tech- Reproductive Health (Georgetown Uni- sound scanning. Ovarian stimulation with niques (ART) adapted to the needs, re- versity, Washington, DC, USA; http:// clomiphene, cycle monitoring for follicu- stricted resources and individual circum- www.irh.org). The contents were adapted lar development and induction stances of the Orotta National Referral to the local needs and focused on the in- with human chorionic gonadotropin Maternity Hospital in Asmara. tended introduction of natural fertility (hCG) for timed intercourse were intro- regulation, hysterocontrastsonography, duced. Clomiphene is on the list of urgent  Pre-conditions ovarian stimulation and intrauterine in- drugs and available in Eritrea. Progester- seminations. In addition, the theoretical one for support (100 mg The first intensive training course was parts should also prepare the residents vaginally) and hCG for ovulation induc- given in March 2011. At that time the for their postgraduate examination in tion were brought in.

J Reproduktionsmed Endokrinol 2013; 10 (1) 45 Infertility Treatment in Resource-poor Countries

As oral contraceptive pills (OCP) are not The residents and seniors were trained in generally accepted and patient compli- transvaginal ultrasound for pelvic explo- ance for taking OCP’s is suboptimal, we ration and cycle monitoring in natural emphasized the possibilities of natural and mildly stimulated cycles. The ultra- methods for fertility regulation [31, 32] sound scans were performed with a in the lectures and practical training ses- Siemens Sonoline SI 250 ultrasound ma- sions. For medical doctors and midwives chine which was donated by Hammer the two-day-method for fertility regula- Forum. Additionally, the Ob/Gyn resi- tion was introduced [33, 34] and under dents and seniors were trained and able supervision the residents were able to to perform hystercontrastsonography teach patients in the outpatient depart- using a newly developed and ready to ment. The two-day-method has been Figure 1: First hysterocontrastsonography (HyCoSy) use kit for hysterocontrastsonography performed by the OB/GYN residents in the Orotta Re- ® proven to be an effective method of fer- ferral Maternity Hospital in Asmara, Eritrea. Nach- ([17], HyCoSy, ExEm Foam , http:// tility regulation for child spacing and to druck mit freundlicher Genehmigung aus: [Der Frauen- www.dikatec-medizintechnik.de/ExEm reduce the number of children [33]. The arzt 6, 2012]. FoamKit.html; http://www.exemfoamkit. very important advantage of natural co.uk) (Fig. 1). methods for fertility regulation is the – ultrasound cycle monitoring imminent health education for women. – assessing ovarian reserve by antral With the German company Gynemed we This health education is urgently needed follicle count [36] prepared “ready to use” kits for one-step, as the knowledge on menstrual cycle – hysterocontrastsonography (HyCoSy standardized intrauterine inseminations physiology, conception probabilities [18]) (IUI) (http://www.gynemed.de/Insemi- throughout the cycle and the prevention – indications for intracervical insemi- nation-Kit.404.0.html) based on the ex- of infectious diseases is rather low in the nation (especially for low total semen perience of others [37]. The kit comes general population [35]. Fortunately the volume, a common problem after male complete with all the necessary materi- interest of Eritrean women in health edu- genital infections) als for one IUI procedure. It is a one-step cation and fertility regulation is high and – one-step intrauterine inseminations system that simultaneously selects and it also allows increased self autonomy. using a simplified swim-up procedure washes high quality for intrauter- for sperm preparation with ready to ine . It recovers high-qual- In February 2012 the second intensive use sets ity, motile sperm from semen in less than course was given at the Orotta National one hour. The method is very simple Referral Maternity Hospital in Asmara At the second visit every morning 10–20 and takes only five minutes of actual to the same five Ob/Gyn residents, six patients with infertility problems were labor time. The semen sample is simply Ob/Gyn consultants and an additional presented. As taught in the first course, placed into a vial at the bottom under the four new Ob/Gyn residents within the basal body temperature charts and basic culture media (a modified Ham’s F-10, postgraduate pro- laboratory tests were discussed and physiological medium with proper pH gram. In between the two intensive analysed. If necessary, further tests were which contains NaCl, KCl, KH2PO4, courses, exchange of information by e- requested and their possible impact on MgSO4.7H2O, NaHCO3, CaCl2.2H2O, mail had taken place. Again the intensive diagnosis and treatment-strategy were Dextrose-Anhydrous, Na-Lactate, Na- course included hands on training under discussed. Pyruvate, EDTA, Na-Alanyl-Glutamine, supervision in the outpatient department (OPD) in the morning and 10 hours of lectures in the afternoon over one week.

Subjects of the second course were in detail: – interpretation of basal body tempera- ture charts with special regard to the endocrinological diagnosis (case dis- cussions and problems) – endocrinological work up (clinics, laboratory tests and interpretation) for amenorrhea, hyperandrogenaemia, luteal insufficiency and bleeding dis- orders – ovarian stimulation protocols with clo- miphene and human menopausal go- nadotropin and adequate monitoring – basic semen analysis with video train- ing [23] – clinical cycle monitoring by assessing cervical index (Insler-score [15]) Figure 2: Sperm preparation with a modified and simplified one-step swim up method for intrauterine insemination.

46 J Reproduktionsmed Endokrinol 2013; 10 (1) Infertility Treatment in Resource-poor Countries water, non-essential and essential Amino international board in February 2012 un-  Discussion Acids, 21 mM HEPES, Human Serum der supervision of the Eritrean authori- Albumin (5.00 g/liter), Gentamicin ties. All five residents passed the exami- The implementation and incorporation (10 mg/liter), Phenolred). During the in- nation and now Eritrea has its first batch of two intensive courses on basic repro- cubation period (approximately 45 min- of specialists in Ob/Gyn educated and ductive and infertility care into an exist- utes), the healthy, motile sperm swim up trained in Eritrea and licensed by the ing Ob/Gyn residency program is not out of the conical cavity and swim down Ministry of Health. only feasible but provides a solid foun- into the medium where they are then dation and method of sustainability to aspirated and used for insemination A follow up of their achievements with a address this important reproductive (Fig. 2). The manufacturer recommends consultation service will be done per health issue. Infertility is an under repre- use of the kit if the ejaculate is normo- Email and a follow up visit is scheduled sented problem in resource-poor coun- zoospermic or slightly oligo- and/or for 2013. tries [38] and recommendations of how asthenozoospermic. An andrological to proceed have been previously very laboratory is not necessary. The semen The Trainee’s Point of View general [5, 39]. preparation may be performed in an OPD Dr. Abraham Yohannes and Dr. Fithawi itself. The residents and the staff were Girmay, Orotta Maternity Hospital, Gynecological endocrinology and infer- trained to prepare semen samples and Asmara, Eritrea: “The intensive courses tility treatment in resource-poor coun- perform intrauterine inseminations. and training in GE and RM opened a tries should be part of an integrated wide gate for further steps in this sub- program of family planning  Achievements ject. The courses were very comprehen- and reproductive health. Governments, sive and all the topics were discussed non-governmental organisations and The Supervisor’s Point of View thoroughly. This has great impact on our health-care professionals should target After two intensive training courses with way of thinking of what we had been mainly at the prevention of infertility. 30 hours of lectures in GER and ART reading in the literature and on adapting Thereby education is the most effective and additional hands on training under it to our case scenarios that pertain to solution to achieve this goal. Education supervision the Ob/Gyn residents and low resource circumstances. We are now programs therefore should address men- the consultants were skilled in the fol- skilled to perform transvaginal ultra- strual cycle physiology, fertility aware- lowing areas: sound for routine pelvic examination, for ness for contraception or optimising fer- – fertility awareness for contraceptive follicular growth follow up, check of tility, infertility-causing factors, sexual- use and optimising fertility for ovarian reserve by counting antral fol- ity and of course applicable techniques achieving a (2008) licles and to do hysterocontrastsono- of infertility treatment. Thereby the – basic gynaecological and reproduc- graphies. In the meanwhile 19 hystero- early diagnosis and treatment of genital tive endocrinology contrastsonographies and 2 IUI (using infections and sexual transmitted dis- – interpretation of basal body tempera- the readymade kit) were done inde- eases is a first important step into treat- ture charts for endocrinological diag- pedently. From the 19 patients 14 were ment. The audience should include mid- nosis found to have patent tubes. In four cases wives, physicians and other health care – clinical and ultrasound assisted cycle a clear diagnose by hysterocontrast- professionals. monitoring sonography was not possible. In one – hysterocontrastsonography for pelvic case an Asherman’s syndrome was diag- Often modern assisted reproductive exploration and assessment of tubal nosed which was confirmed by hysteros- techniques are high cost interventions. patency alpingography later. For example, by Therefore research is needed and experi- – basic sperm analysis doing saline injection for hystero- ences must be gained to develop simpli- – performance and interpretation of sonography four patients were diag- fied approaches: simplification of diag- postcoital tests nosed to have big submucous myomas. nostic tests, simplification of assisted re- – intrauterine inseminations with a These possibilities of vaginal ultrasound productive techniques and at a low cost modified swim-up procedure for scanning with saline and/or contrast level. In our experience Fertility aware- sperm preparation after ovarian medium are a great step forward be- ness methods play an important role as a stimulation with clomiphene citrate cause laparoscopic techniques are diagnostic and interventional tool and it – basic documentation of interventions available only in exceptional cases in can easily be taught. Eritrea yet. Hysteroscopy is not possible. During the one-year interval the interest Despite all these achievements we suffer In addition, ultrasound machines for in infertility care had increased. The Ob/ from shortages of the contrast medium vaginal and abdominal scanning are Gyn residents were much more aware of and catheter systems for hystercontrast- available in most gynaecological and diagnosing infertility problems and see- sonography, HMG and HCG for ovarian obstetrical units in developing countries ing patients for these reasons in the out- stimulation and , in the meantime. The Eritrean experi- patient department. The Ob/Gyn resi- progestrone for lutueal phase support ence shows that with some hands on les- dents who completed both intensive and ready made kits for IUI. This list was sons, a routine vaginal ultrasound for courses may now work independently. given to the Department of Family and pelvic exploration and cycle monitoring Their knowledge was proved by taking Reproductive Health. We see many pa- can easily be implemented in the infertil- their postgraduate examination in ob- tients in urgent need of infertility care in ity care of patients. Moreover, we as- stetrics and gynaecology in front of an Asmara, Eritrea.” sured ourselves that hysterocontrast-

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