1. Dr. Osama Oro Shareef. Dr. Suliman Osman . Dr. Ashraf Kamal .
Sudanese Human Reproduction & Embryology Society Assessment and treatment for people with fertility problems at primary level
Dr. Osama Oro Shareef.
Dr. Suliman Osman .
Dr. Ashraf Kamal .

2. Definition of infertility
A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner. .(NICE clinical guideline 156)

3. Introduction
It is estimated that infertility affects 1 in 7 heterosexual couples in the UK. Since the original NICE guideline on fertility published in 2004 there has been a small increase in the prevalence of fertility problems, and a greater proportion of people now seeking help for such problems.(NICE clinical guideline 156)

4. Introduction cont..
The main causes of infertility in the UK are (percent figures indicate approximate prevalence):
unexplained infertility (no identified male or female cause) (25%)
Ovulatory disorders (25%)
Tubal damage (20%)
Male factors (30%)
Uterine or peritoneal disorders (10%).
In about 40% of cases disorders are found in both the man and the woman. Uterine or endometrial factors, gamete or embryo defects, and pelvic conditions such as endometriosis may also play a role. .(NICE clinical guideline 156).
IN Sudan according to study published in 2015, it was found that causes of infertility indicating ICSI in Sudanese couples were :
Male factor 42,9% , female factors 25,1% , combined male and female factors 3,7% , unexplained 28,3%.()

5. How to assess infertile couples:-
* History: (Age , regularity of the cycle, duration of marriage , parity, history of miscarriages, history of ectopic, hairshitism , glactorrhea, sexual life and problems, history PID, past medical history, past surgical history ..ect.
* Examination : general examination, BMI.
Speculum examination.
Transvaginal ultrasound.
* Investigation: -
1- Seminal analysis:

6. The results of semen analysis conducted as part of an initial assessment should be compared with the following World Health Organization reference values:
semen volume: 1.5 ml or more.
pH: 7.2 or more
sperm concentration: 15 million spermatozoa per ml or more.
total sperm number: 39 million spermatozoa per ejaculate or more.
total motility (percentage of progressive motility and non- progressive motility): 40% or more motile or 32% or more with progressive motility.
vitality: 58% or more live spermatozoa
sperm morphology (percentage of normal forms): 4% or more.

7. Repeat confirmatory tests should ideally be undertaken 3 months after the initial analysis to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia) has been detected the repeat test should be undertaken as soon as possible. .(NICE clinical guideline 156).
2- Day 2-3 follicle stimulating hormone & luetinizig hormone :
A level exceeding 25 mIU/ml (about 12mIU/ml using current assays) has been correlated with a very low chance of pregnancy, The basal FSH level at the beginning of menstrual cycles can be divided into : three phases. In the first phase, fertility is normal and FSH is always low. In the second phase, FSH is intermittently elevated and fertility is declining. In the last phase, FSH is always elevated and fertility is nil.

8. 3- HSG
Women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy or endometriosis) should be offered hysterosalpingography (HSG) to screen for tubal occlusion because this is a reliable test for ruling out tubal occlusion, and it is less invasive and makes more efficient use of resources than laparoscopy , Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time. (NICE clinical guideline 156).
**Please look carefully to the position of the tubes to rule out tubal adhesions .

9. Indications for referral to infertility centers :
The woman is aged 36 years or over.
Prolonged history of infertility, many trials of ovulation induction.(NICE clinical guideline 156).
There is a known clinical cause of infertility or a history of predisposing factors for infertility. . (NICE clinical guideline 156).
Results of Ovarian reserve tests are suggestive of low ovarian reserve.

10. Who are candidates for treatment at primary level:
Women aged less than 35 years, with ovulatory problems.
Couples with un explained infertility .
Mild male factor with single variant deviated from normal.

11. Aim of management:-
Timed sexual intercourse either in natural or induced cycle, by which we mean to time sexual relationship at the time of ovulation.
A: In natural cycle :-
we don’t interfere , just ask the patient to come for U\S on day 7-9 of her period, to see the diameter of the dominant follicle and endometrial thickness.
Note that:-
1- Although transabdominal ultrasonography has been used, transvaginal ultrasonography (TVUS) is the best means that we have to follow the course of follicular growth and development as it is rapid, non-invasive, with highly visual approach to following the fates of individual follicles and cohorts of follicles .

12. 2- We aim to reach a dominant follicle of 18 mm or more and endometrial thickness between 8- 14mm thickness with trilaminar (halo)appearance-outer echogenic and inner hypo echoic, hyper echoic isoechoic end at the time of triggering.
3-Schedule the next U\S keeping in mind that Follicle destined to ovulate increase linearly in size at the rate of 1-2mm/day.
4- Trigger when the dominant follicle reached 18 mm with 5000 I.U of HCG, and time sexual relationship 36 hours after injection.

13. B: Induced cycle:-
Aim is to produce 2 -3 follicles by the time of triggering to increase chances of pregnancy.
We use either :-
Clomophine citerate.
Aromatase inhibitors ( eg :letrozole).
Gonadotrophins alone or with one of above mentioned drugs.

14. Clomophine citerate
Action:- It is anti-estrogenic agent act by blocking estradiol receptors in the hypothalmus Invokes the negative feedback mechanism Release of FSH from AP and consequent follicular development and esteradiol production. Dose:- The most common dose used is mg per day for 5 days starting from day 2-3 of the cycle. Results:- Data from literature said it has an ovulation rate of 73%, pregnancy rate of 36%. Limitations :- 1-Failure 2- negative effect on the endomertrim 3- should not be used for more than 6 months ,

15. Aromatase inhibitors
Action:- They suppress estrogen synthesis by blocking aromatase enzyme so they release hypothalamus from the negative feedback effect of estrogen, almost free of side effects.
Dose :- Letrozole is given in a dose of 2,5-5 mg per day for 5 days starting from day 2-3 of the cycle.
Results:- 2 meta-analysis of studies comparing pregnancy rates with CC and letrozole showed slight superiority of letrozole.
Advantages : No negative effect on the endometrium.
Limitations:- Its use is still in its infancy, so many question about its safety remain to be answered.

16. Low dose Gonadotropin therapy
Aim: is to obtain the ovulation of 1-3 follicles, it employs a dose that is not supra-physiological but reaches the threshold for follicular response, so practically can eliminate the occurrence of OHHS.
Dose: The classic dose is 75 IU remain unchanged till you reach the criteria for hCG administration, small incremental dose rise is used if you don’t reach the target .

17. Triggering
When follicles reach a size of 18 mm give 5000mg of hCG IM and schedule sexual relationship 36 hours after triggering.
Put in mind that we must synchronize follicular maturation with endometrial growth.

18. Luteal phase support
Luteal phase support forms an integral part of of controlled ovarian hyperstimulation and largely contributes to successful outcome.
An optimal dose of mg of micronized progesterone has been used, but needs farther trial to reach consensus.
No evidence in literature to support continuation beyond the 1st positive hCG.
Success rate seem similar with I.M and vaginal administration.
For simple induction use oral progesterone (duphastone 10 mg) every 12 hours.

19. Midsagittal view of the uterus
Midsagittal view of the uterus. The cervix is to the right of the image and the fundus is to the left. The endometrium is well demarcated and shows a pronounced, thick ‘‘triple- line’’ pattern associated with a higher probability of implantation.

20. Image of an ovary with three dominant follicles visible in the plane of section. The image was acquired 24 hours prior to oocyte retrieval. The thick walls of the follicles are consistent with collection of oocytes with a high probability of fertilization.

21. THANK YOU