Your Infertility Dilemma’s…: The Expert’s Final Verdict Prakash Trivedi
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Perspective—Infertility1

 
PRELIMINARY EVALUATION OF INFERTILE COUPLE
Q 1: What's the role of routine D and C with diagnostic laparoscopy today (PT)?
With availability of good transvaginal sonography machines and hormonal evaluation most of the advanced infertility centre don't do this procedure in most of the patients. In only selected cases microlaparoscopy with hysteroscopy and if necessary endometrial RNA PCR for Koch's is done. Only D and C laparoscopy is inadequate for diagnosis, quite often a normal finding is expected in > 80% of cases. A history, good clinical examination to rule out thyroid problems, hirsutism and galactorrhea is important. Thorough examination of male factors and semen examination is mandatory.
 
ROLE OF HORMONAL ASSAY
Q 2: Hormone evaluation, is it an underutilized tool? When and how you will do in your practice? (AM)
Hormone evaluation though advised frequently is definitely underutilized for applications in clinical practice to tailor make patients treatment protocol, i.e. to use it according to the specific requirement of a particular patient.
  • 30% of infertility patients have hormonal imbalance in the form of PCOS. Evaluation of serum LH and FSH is important as their ratio is > 2 in 30 to 40% of women with PCOS. Evaluation of serum testosterone (free) and DHEAS helps to 2detect the source of androgens (ovary/adrenal) in patients with hirsutism. Blood sugar estimation with insulin levels helps us in diagnosing glucose intolerance or frank diabetes along with the presence of peripheral hyperinsulinemia.
  • Hypothyroidism is associated in 10% patients and hyperprolactinemia in 5% of PCOS women therefore need evaluation.
  • Basal serum FSH, LH and estradiol estimation is a good option in all patients especially if they are over 30 years or their ovarian volume is on the lower side or they have had history of pelvic infection or pelvic surgeries / endometriosis in the past. These hormones should also be checked in all patients presenting with oligomenorrhea/amenorrhea irrespective of age. Ovarian clock is seen to tick off faster in a lot of women than what their chronological age would suggest and all these women need early assessment of all basal hormones with active management of infertility (AM).
Q 3: What is the drug of choice for Hyperprolactinemia—bromocriptine or cabergoline? Why? (KR)
Bromocriptine is a D2 receptor agonist. Therapy should be started at a dose of 0.625 mg at night; after 1 week, a morning dose of 1.25 mg can be added. The dose should be increased by 1.25 mg per week; a daily dose of 5–7.5 mg is usually required to restore menses and normalize prolactin levels. Side effects including nausea, orthostatic hypotension and depression are minimized by taking the drug at night.
Cabergoline is a long-acting D2 receptor agonist that is taken once or twice per week. It is more effective in reducing prolactin and restoring ovulatory cycles (90% and 85% of patients, respectively) than is bromocriptine (59% and 52%) at doses of 2.5–5 mg twice daily. Cabergoline also reduces the size of macroadenomas in 90% of patients, and is better tolerated than 3bromocriptine, with fewer and milder side effects. Therapy is started at a dose of 0.25 mg per week and increased to a maximal 1 mg twice weekly; 0.25–0.5 mg is usually sufficient to normalize prolactin levels.
Pregnancy: The risk of symptomatic enlargement of a microadenoma during pregnancy is about 1–3%, so dopamine agonists can be stopped once pregnancy is confirmed. However, macroadenomas carry a greater risk of growth during pregnancy (reported rates are 15–35%) and therefore dopamine agonist therapy should be continued. Although cabergoline is not licensed in pregnancy, no adverse effects have been reported.
 
Certain Facts about Cabergoline
  • Cabergoline is now the first-line treatment for microprolactinoma and macroprolactinoma
  • MRI of the pituitary has superseded CT as the first-line investigation
  • Continuation of cabergoline therapy is advisable during pregnancy in patients with a macroprolactinoma, but can be stopped in those with a microprolactinoma.
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Dr Kamini A Rao
dgo, dorcp, mch, frcog, pgdmle (law) fnams
  • Medical Director, Bangalore Assisted Conception Centre
  • President, Indian Society for Assisted Reproduction (2006– 2007)
  • President, Federation of Obstetrics and Gynecological Societies of India (2000–2001)
  • Chairperson, Women's Sexual and Reproductive Rights Committee, International Ob. Gyn Federation (FIGO)
  • Member, National Advisory Committee on Assisted Reproductive Technology
  • Stem Cell Research in collaboration with the National Centre for Biological Sciences with Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR)
  • South India's first ICSI, first Laser Assisted Hatching baby and first SIFT Baby
  • Advanced work in the field of Foetal Medicine and Surgery for the identification of chromosomally and genetically abnormal fetuses
Address:
6/7, Kumara Krupa Road
Highgrounds, Bangalore 560 001
Tel:91-80-22260880/41138255 Fax: 91-80-22250465
 
Editor's Comment
Dr Kamini Rao, a dedicated, intelligent, committed lady towards the health and rights of woman. Her work in 5all sections of Medical profession and even social cause is always to perfection. Her vast knowledge in the field of ART and Genetics is a treasure of India. Her Leadership quality is par excellence as FOGSI President 2000–2001, ISAR President 2006–2007 and representation at FIGO. Her biggest asset is as a mass motivator concerned about juniors and their progress. She is a role model for any woman professional in the world.6
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Dr Abha Majumdar
Head of Unit of IVF and Human Reproduction
Department of Obstetrics and Gynaecology
Sir Ganga Ram Hospital, New Delhi, India
Dr Abha Majumdar the recipient of 7 gold medals and the president's medal for being the best medical graduate for the year 1975. She was felicitated on Doctors day by Dr BC Roy's award, on 1st July 1999, for her outstanding contribution towards medicine and her field of specialty. She has also been awarded Nations Vikas Ratan Award by the Nations economic development and growth society in the year 2002 and Chitsa Ratan Award Has been recognized for awarding FOGSI certificate for basic training in infertility and IUI and advanced infertility training by FOGSI for 15 days. She has been appointed by the National Diplomate Board as teacher for awarding Fellowship in Reproductive Medicine (2 years Fellowship) to postgraduates in obstetrics and gynecology. Chairperson for the Infertility sub-committee of the Association of Obstetrics and Gynecology of Delhi. She is the first Vice President and founder member of “Indian Fertility Society” (IFS).
Tel res. 011-28744716, 28744206
Tel Genesis Clinic 011-28742454, 28745692
Tel fax 011- 422517717
 
Editor's Comment
Dr Abha Majumdar is a woman with phenomenal potential. Her knowledge in the field of ART and allied subjects is exceptional. Her keenness to teach and also take care of the Generation Next is an asset. Inspite of her success and status she maintains a balanced profile. She is capable of handling any job assigned to her. She is committed to her professional commitment.8
Q4: How important is sonography in assessing the female reproductive tract in infertility? (NM)
 
Assessment of the Female Reproductive Tract
The female is responsible for 40% of causes of infertility and contributes in another 20% of mixed causes in the couple. Out of this the ovulatory dysfunction (30%) and tubal factor infertility (25%) are major factors. The female reproductive tract is usually evaluated by the busy gynecologist by a per speculum and a per vaginum examination and then an HSG is usually ordered and then a transvaginal scan is ordered and later followed with other tests. These usually take time and frustrate the patient and the doctor.
We advocate a transvaginal scan at the very first visit of the couple by the infertility specialist himself/herself just after a per speculum exam, this will enable the clinician to come to a diagnosis on the very first visit regarding problems in vagina, cervix, uterus, endometrium, endometrial cavity, tubes, adnexa, ovaries and general pelvis as a whole. Such an examination helps to decide the further treatment line and actively manage infertility by a single day evaluation test and active management protocol (Rajan, Malhotra) (2000).
 
ROLE OF SONOGRAPHY, 3D-4D AND COLOR DOPPLER IN INFERTILITY
Q5: What are the criteria for the sonographic assessment of ovulation?(NM)
 
Prediction of Ovulation
A small echogenic mass that is thought to represent the cumulus oophorus may sometimes be noted projecting into the follicle. Visualization of the cumulus oophorus has been reported in 80 percent of follicles greater than 17 mm in diameter. Ovulation is reported to be within 36 hours of seeing the cumulus. However, Zandt-Stastny has challenged this view and has noted that the cumulus is only 100 to 150 microns in size 9and would not be expected to be visualized by sonography. Zandt-Stansky et al have suggested that structures imaged in follicles thought to represent the cumulus are artifacts. After the LH surge, the theca tissue becomes hypervascular and edematous and the granulosa cell layer begins to separate from the theca layer. This is appreciated sonographically as a line of decreased reflectivity around the follicle. Picker et al in 1987 suggested that this sonographic sign means impending ovulation within 24 hours. Jaffe and Ben-Aderet in 1984 described the same sign, which they called a ôdouble contourö and suggested that it occurs a few hours before ovulation. Within 6 to 10 hours before ovulation, separation and folding of the granulosa cell layer produces a crenation or irregularity of the lining of the follicle. This has also been suggested as sign of impending ovulation. Unfortunately, despite the fact that there are a number of sonographic signs that have been described to precede ovulation, there is currently no sonography sign that predicts exactly when ovulation will occur, the signs only give evidence that the time of ovulation is nearing. The mean peak diameter before ovulation reported by Kerin et al was 23.6 + 0.4 mm. However, there are considerable differences in the same.
Hence, the potential signs of impending ovulation are:
  • Presence of a dominant follicle (usually more than 16 to 18 mm)
  • Anechoic area, double contour, around the follicle (possible ovulation within 24 hrs)
  • Separation and folding of the follicle lining (ovulation within 6 to 10 hrs)
  • Thickened proliferative endometrium (described later)
 
Confirming Ovulation
Sonography does appear to be very reliable in confirming ovul ation once ovulation has occurred. Disappearance of the follicle is noted in 91 percent of 10cases after ovulation and a decrease in follicle size occurs in another 9 percent. Other signs suggesting that ovulation has occurred are the appearance of cul-de-sac fluid, particularly when it was not present in a previous scan, or the development of intrafollicular echoes suggesting the formation of a hemorrhagic corpus luteum.
Q6: What are the signs of anovulation? (NM)
 
Ovary in Anovulatory Cycles
In an anovulatory cycle, ultrasound imaging of the ovaries will reveal either a lack of any follicular development, particularly in the hypogonadotropic hypogonadal patient WHO type I or a few non ovulatory (less than 11 mm) follicles. A dominant follicle larger than 16 mm in diameter will not develop. A cyst may also be associated with anovulation. Anovulation with PCOD will often have enlarged ovaries greater than 8 cm3 in volume with multiple small subcapsular follicles less than 10 mm in diameter. However, normal sized ovaries do not rule out PCOD. Anovulation can be diagnosed when serial scans do not show development of a follicle. A mature corpus luteum is noted sonographically in about 50 percent of patients after ovulation. If pregnancy does not occur the corpus luteum generally degenerates and disappears just before menstruation. Corpus luteum cysts may be 4 to 6 cms in diamter and occasionally even large but are more commonly 2.5 to 3 cms in diameter. They may persist for 4 to 12 weeks and may be responsible for suppressing normal follicular development until they resolve.
Q7: What are the sonographic signs of PCOD?(NM)
In PCOD the ovaries are increased in size. The mean volume of the ovary is 12.5 cms3 with a range from 6 to 30 cms. The classical anatomic criteria are not present in all patients with clinical or endocrine findings suggestive of PCOD. Therefore, an ultrasound 11showing ovarian enlargement can help make the diagnosis, but a normal ultrasound examination with normal size ovaries does not rule out PCOD if the clinical or biochemical abnormalities characteristic of the syndrome are present. Ultrasound may also suggest the diagnosis of PCOD in a patient with normal sized ovaries and the clinical and or endocrine criteria of PCOD by confirming anovulation.
Enlarged ovary (more than 8 cms3)
Multiple small cysts (0.2–0.6 cm)
Anovulation (lack of follicular development)
Resting or follicular endometrium
Q8: What is endometrial appearance in different phases of the menstrual cycle? (NM)
The endometrial cavity should be visualized as a separate entity within the uterus in virtually all menstruating patients. The endometrial cavity is generally centrally located in the uterus. The cyclic histological changes and changes in thickening of the endometrium with hormonal stimulation are well known. This cyclic changes of the endometrium can be imaged using transvaginal ultrasound during the different phases of the menstrual cycle. The hormonal and ovulatory status of the patients can be assessed by evaluating the endometrial patterns.
Sakamoto described the characteristic sonographic images noted through the menstrual cycle in 1985. The proliferative endometrium is characterized by (a) the presence of a well defined three line sign, (b) a hypoechogenic functional layer, and (c) a minimal or absent posterior acoustic enhancement. The three line sign is formed by the central hyperechoic reflection representing the endometrial cavity and the additional hyperechoic reflection representing the thin developing layer of endometrium. There is also a surrounding hypoechoic halo. During the luteal phase, the endometrium is hyperechoic, with posterior 12enhancement and absence of the three line sign and halo.
Early proliferative phase: The anechoic central echo noted during early menses is replaced by a hyperechoic central line and the endometrium begins to thicken, forming the three line sign. The general hypoechogenic character of the functional layer of the proliferative endometrium is thought to be related to the simple configuration of the glands and blood vessels. The outer lines represent the endometrium and the interface between the endometrium and myometrium. These outer lines may thicken as the estrogen stimulation increases and the follicular phase progresses and blends into a thickened hyperechoic endometrium during the secretory phase. In the follicular phase, the halo which is about 2 mm thick and surrounds the endometrium, is present. There is no posterior enhancement. A follicular phase endometrium greater than 6 mm thick has been associated with a serum estradiol level over 200 pg/ml and a developing follicle greater in diameter.
Late proliferative phase: There is continued thickening of the endometrial echo complex in the late proliferative phase. The halo is still present. The endometrial complex is still imaged as three parallel lines, but the outer lines may begin to thicken. The total endometrial thickness increases and may reach 10.9 mm or greater in total thickness. There is no posterior enhancement. Cervical mucus may occasionally be imaged as hypoechoic density in the endocervix near the time of ovulation.
Luteal phase: In the luteal phase the endometrium is thickened and is imaged as a homogeneous hyperechoic density with posterior enhancement and loss of the surrounding halo. The three line sign is gone. The rate of increase of thickness slows and the endometrial echo complex soon achieves its greater 13anterior posterior dimension. The echogenicity of the endometrium becomes hyperechoic after coiling and lengthening of the endometrial glands and the production of mucus and increased tortuousity of the glands and blood vessels. Interestingly, acoustic enhancement is usually associated with cystic or fluid filled structure that are hypoechoic, yet is characteristically seen posterior to the luteinized endometrium. Acoustic enhancement occurring posterior to a hyperechoic structure is unusual and is thought to be related to the increased vascularity of the endometrium. Posterior enhancement is assessed in the anterior posterior pelvic (AP-Pelvic) image plane, since some posterior enhancement may be noted in a trans pelvic (T-Pelvic) plane even during mid to late follicular phases. Although it is not known why enhancement is noted in the T-Pelvic plane, one explanation is that small anechoic areas may be noted in the endometrium which probably represent areas of hemorrhage into the endometrium with endometrial degeneration and herald onset of vaginal bleeding.
Minimally stimulated or single line endometrium: Patients with low estrogen or excess androgen have generally have a single line endometrium similar to a late menstrual endometrium. Care must be taken when interpreting or reporting such measurements as to whether full thickness of both layers of endometrium or only one layer is being used. Since it is generally simpler just to measure the full endometrial thickness this is usually the measurement reported. The average thickness of the proliferative endometrium to be 8.4 mm + 2.2 mm while the secretory endometrium is 9.6 + 3.4 mm.
Endometrial motion: The endometrium can be seen to move during real time ultrasonographic imaging. This movement can be quite impressive when first seen.14
 
Endometrial Changes
  1. Endometrial growth in follicular phase.
  2. Increase in glands but quiescent till ovulation.
  3. At ovulation the glands become tortuous and formation of spiral arteries occur.
  4. During Implantation time (day 20, 21 and 22) the endometrium is thick, edematous and contains predecidual cells. Epithelial lining has a mucus film and microvilli and pinopodes. These are not present at day 16 and vanish by day 24 in both spontaneous or induced cycles. These changes and pinopodes are said to help in the process of anchoring and sustaining the embryo.
  5. Extensive biochemical changes also occur in the endometrium which are not fully understood and involves synthesis of various proteins sialic acid, 3 fucosyl-N acetyl lactosamine, electro negativity, etc. Retinoic acid (RAR) evolves all these changes and these are deficient in primary infertility cases.
  6. Electro charges, mitotic changes, molecular biological changes are also activated following ovulation.
The endometrial changes at all stages are regulated by steroids.
Q9: What is the importance of uterine biophysical profile in improving conception rate? (NM)
Ultrasound (TVS) offers a simple, reliable, reproducible, quick and non invasive method for assessing the female pelvis.
 
Ultrasound Technique for Uterine Biophysical Profile
To perform the UBP special care should be taken. The following guidelines are recommended: Apple baum 96.
  1. To determine the presence of a 5-line appearance, information from both the transabdominal and 15transvaginal studies may be useful. For example, although a 5-line appearance may be noted transabdominally, it may not always be possible to see it endovaginally due to uterine position (and vice versa). In this case, a 5-line appearance is considered to be present and endometrial vascular penetration may be estimated when performing the endovaginal study.
  2. Perform the Doppler study slowly. The flow of blood in the endometrium is of low velocity, it may take time for the ultrasound machine to register the presence of blood flow and create the image. If one sweeps through the endometrium too quickly, flow may not be seen. Additionally endometrial blood flow has a mercurial personality—it may appear as if it comes and goes. It may also appear in some areas and not others. Do not observe hastily.
  3. Endeavor to make the endometrium as specular a reflector as possible. Use the techniques of manual manipulation of the anatomy and probe pressure to achieve this.
  4. Scan endovaginally both coronal and sagittal. There may be a difference in how well the blood flow is imaged.
  5. When measuring the endometrium in the A-P dimension, try to obtain the value when no contraction affecting it is present. Contractions may affect this value. Also when possible, obtain the measurement in a standard plan such as when both the endometrial and cervical canals appear continuous.
 
The Uterine Biophysical Profile
In our experience, certain sonographic qualities of the uterus are noted during the normal mid-cycle. These include:
  1. Endometrial thickness in greatest AP dimension of 7 mm or greater (full-thickness measurement).
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  2. A layered (5 line) appearance of the endometrium.
  3. Blood flow within Zone 3 using color Doppler technique.
  4. Myometrial contractions causing a wave like motion of the endometrium.
  5. Uterine artery blood flow, as measured by PI, less than 3.0.
  6. Homogeneous myometrial echogenicity.
  7. Myometrial blood flow seen on gray-scale examination (internal to the arcuate vessels).
The uterine scoring system for reproduction (USSR) comprises evaluation of the following parameters:
  1. Endometrial thickness (full-thickness measured from the myometrial-endometrial junction to the endometrial-myometrial junction).
  2. Endometrial layering (i.e., a 5-line appearance).
  3. Myometrial contractions seen as endometrial motion).
  4. Myometrial echogenicity.
  5. Uterine artery Doppler flow evaluation.
  6. Endometrial blood flow.
  7. Gray-scale myometrial blood flow.
Each parameter is scored as follows:
  1. Endometrial thickness
    1. < 7 mm = 0
    2. 7–9 mm = 2
    3. 10–14 mm = 3
    4. > 14 mm = 1
  2. Endometrial layering
    1. No layering = 0
    2. Hazy 5-line appearance = 1
    3. Distinct 5-line appearance = 3
  3. Myometrial contractions (seen as wave-like endometrial motion high-speed playback from videotape)
    1. 0 contractions in 2 minutes (real-time) = 0
    2. 3 contractions in 2 minutes (real-time) = 3
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  4. Myometrial echogenicity
    1. Coarse/inhomogeneous echogenicity = 1
    2. Relatively homogeneous echogenicity = 2
  5. Uterine artery Doppler flow
    1. PI-3.0 = 0
    2. PI-2.99 = 0
    3. PI-2.49 = 1
    4. PI < 2 = 2
  6. Endometrial blood flow within Zone 3
    1. Absent = 0
    2. Present, but sparse = 2
    3. Present multifocally = 5
  7. Myometrial blood flow internal to the arcuate vessels seen on gray-scale examination
    1. Absent = 0
    2. Present = 2
The values assume a technically adequate ultrasound examination with no abnormalities of uterine shape or development, no other gross uterine abnormalities (e.g. significant masses) and a normal ovarian cycle (e.g. without evidence of ovarian-uterine dyscoordination). A male factor component to the infertility is not present.
In our limited experience Applebaum with this system thus far, a USSR “perfect score” of 20 has been associated with conception 100% of the time. (The number of patients in which we predicted successful conception cycles based upon the UBP and USSR, perfect score was 5. This group included 2 spontaneous cycles (non-IVF, non-IUI), 2 IUI and 1 IVF). Scores of 17–19 (10 patients) have been associated with conception 80% of the time. Scores of 14–16 (10 patients) have a 60% chance, while scores of 13 or less (25 patients) have resulted in no pregnancies.
Absent endometrial flow, despite highest values for the other parameters, has always been associated with no conception.
Our initial observations were based upon experiences with both “normal” non-infertility patients and 18patients treated for infertility. The observations were categorized and then applied as a system to patients with diagnosed infertility from all corners. I did not divide the patient population into sub-groups based upon treatment protocol, age, cause etc. (NM)
Q10: What is the importance of ultrasound in assessment of male infertility? (NM)
Transvaginal ultrasound today is the modality of choice in evaluating male and female infertility as a first step investigation and should be used by the clinician in the consulting chamber along with pelvic examination. It is like marrying palpation with imaging.
 
Ultrasound Assessment of the Male Partner
Male factor infertility today comprises almost 40% of the causes in an infertile male. The modern life style and additives in food have became a major environmental cause of oligoasthenospermia. The function of male genital system encompasses the central nervous system (hypothalamus and pituitary), the adrenal glands, the testes, the epididymis, the seminal vesicles and the prostate gland. Any malfunctions of any of these may affect the male reproductive capacity.
Scrotal and transrectal (TRUS) are used in evaluation of the reproductive tract disorders. Color flow imaging is used for assessment of varicocele. 3-D is used for testicular volume and seminal vesicle and prostate evaluation. Computed tomography and endorectal Magnetic Resonance Imaging can also be used.
Scrotal sonography is performed with patient in supine position using a small part probe 7.5–10 MHz linear probe. This can evaluate the testis for size, shape, hydrocele, benign tumours, atrophy, malignancy, orchitis, torsion, haemorrhage, focal lesions, etc. Ultrasound imaging is very sensitive in testicular evaluation.19
Transrectal Ultrasonography (TRUS) is an excellent approach for visualising the seminal vesicles, prostate and ejaculatory ducts. With TRUS we can assess obstructions, absence or hypoplasia of seminal vesicle and ejaculatory ducts. TRUS is an excellent screening test for ejaculatory duct pathologies and is indicated in all men with severe oligospermia and a low volume ejaculate.
Q11: What are the vaginal and cervical factors which can be evaluated by sonography? (NM)
Vagina and the cervix is the first obstacle that the spermatozoa have to negotiate on their way to reach the oocyte. Vaginal septae, stenosis, vaginismus and coital difficulties are best assessed by a per speculum examination, however TVS helps to locate vaginal cysts and vaginal infiltrations.
Cervix is composed of cervical glands which secrete mucus in response to estrogens stimulation and this secretion assists passage of sperms. About 5–10% of causes of infertility are due to cervical factors, which may be anatomical or functional abnormalities.
Transvaginal ultrasound can very accurately assess both anatomical and functional problems of the cervix.
Assessment of cervicitis, nabothian cysts at internal os, poor cervical mucus, cervical agenesis and cervical stenosis is possible and should be done. Cervical conisation and cervical infections should always be kept in mind and assessed for clinically before a TVS scan.
Q12: What are the female pathologies related to infertility which can be diagnosed by ultrasonography? (NM)
Uterus is the place for embryo implantation and pregnancy continuation. The normal adult uterus is a muscular organ 6–10 cm in length and 3–5 cm in width and has a unique capacity to grow and expand to hold a full term fetus during pregnancy.20
TVS can accurately asses the uterine factors and with addition of fluid (saline) by sonohysterography the cavity can be accurately studied, with addition of color flow imaging, color doppler studies of uterine artery, power angio; the spiral artery and endometrial vascularisation can be evaluated to score the uterus for favourability of implantation (uterine scoring system for reproduction)(Applebaum, Dalal, Malhotra).
Leiomyomas are one of the most common benign neoplasma in women and have been reported to occur in up to 40 percent of women over the age of 35.
Uterine leiomyomas do not have a true capsule and there may not be an acoustic interface and therefore no echo resulting from a structural boundary. A submucosal myoma within the uterine cavity may be imaged as an area of increased echogenicity and may be mistaken initially for blood, mucus or a polyp in the uterine cavity.
 
Endometriosis
These cysts are homogenous with a low level echo patterns with good through transmission. They have fine stippling pattern filling the whole of the cyst. Transvaginal ultrasound is the most useful tool for screening for fibroids. The uterus is enlarged with contour deformity (Fibroid causing contour problem) and focal masses with different echogenecities (Hypoechoic usually, hyperechoic when calcified and may be isoechoic also).
 
Congenital Anomalies
Congenital anomalies of the uterus occur in about 0.1–0.4% of general population of women and are due to the embryological problems in Müllerian system. Congenital anomalies are a significant cause of recurrent pregnancy loss. About 80% of women with congenitally abnormal uterus may have no problems 21in conceiving but anomalies are responsible for almost 20% of recurrent pregnancy loss and hence should be carefully looked for and treated whenever encountered during infertility evaluation.
Uterine congenital anomalies can be diagnosed by HSG, TVS, contrast sonohysterography, hysteroscopy and laparoscopy and by a MRI 3D HSG and TVS without saline contrast are the commonest methods. The anomalies which can be diagnosed are bicornuate uterus, unicornuate uterus, intrauterine septa (complete, incomplete or arcuate).
 
Sonohysterography
Instillation of sterile saline into the uterine cavity under ultrasound guidance (TVS) will let us study the uterine cavity without any radiation exposure and without exposure to contrast media. The saline distended cavity is anechoic surrounded by symetric endometrial lining. Sonohysterography will enable the diagnosis of Asherman's Syndrome or intrauterine adhesions, polyps, submucous fibroids and uterine septa. HYCOSY or contrast hysterosalipingosonography involves the use of a sonography contrast media. In the future in the better understanding this may replace the more invasive HSG as a first time investigation of the infertile female.
 
Endometriosis of the Uterus (Adenomyosis)
Endometriosis is a disease in which typically the endometriotic implants are scattered in various extra uterine locations. However sometimes the ectopic endometrium goes into the myometrium and causes adenomyosis. These endometrial tissue starts to proliferate inside the myometrium and tends to bleed on progesterone withdrawl during the menstrual cycle thus giving the uterus a typically speckled appearance resembling ‘Salt’ and ‘Pepper’ (Hyperecohic areas and hypoechoic areas). Depending on the extent of lesion 22and the severity of disease the uterus will appear enlarged and sometimes all of the adenomyosis areas may together look like a fibroid (Adenomyoma).
 
ROLE OF TRANSVAGINAL COLOR DOPPLER IN INFERTILITY
Q 13: What's the role of sonography and color doppler in Infertility ? (NM)
The advent of transvaginal Color Doppler Sonography has added a new dimension to the diagnosis and treatment of infertile female. Color Doppler innovation is a unique non-invasive technology to investigate the circulation with organs like uterus and ovaries. Dynamic changes occur almost every day of the menstrual cycle in a reproductively active female. These events are picked up very well by transvaginal Color Doppler and definite conclusions can be drawn regarding the diagnosis, prognosis and treatment of infertile patients. As the Vaginal Probe lies close to the organs of interest various vessels supplying these structures can be studied in detail like the uterine artery, ovarian artery and their branches.
 
Study of Menstrual Cycle by Color Doppler
It is very important to study the whole of the menstrual cycle by transvaginal color doppler during the evaluation of infertility. It provides vital information about follicular dynamics like blood flow to the growing follicle, the vascular supply of the endometrium and corpus luteum vascularization which are very important for a successful outcome in terms of pregnancy.
 
Changes in the Ovary
The ovary measure about 2.2 to 5.5 cms in length, 1.5 to 2.0 cms in width and 1.5 to 3.0 cms in depth and are recognized by the presence of follicle of different sizes. 23The blood is by ovarian artery via the infundibulo pelvic ligament and ovarian branch of the uterine artery. There is anastamosis between the two sources of blood supply. The primary and secondary branches of the ovarian artery grow along with the development of the follicle. Dominant follicle within the ovary can be recognized by transvaginal color doppler by day 8th or 10th of the cycle by a ring of angiogenesis around it, when compared to the subordinate follicles which do not demonstrate this. These vessels become more abundant and prominent as the follicle grows to about 20–24 mm in size.
 
The Phases are as follows
In general the index values are high in the early part of menstrual cycle and fall as ovulation approaches. According to Kurjak et al the RI in the early proliferative phase is 0.54 + 0.04 and declines the day before ovulation when it is about 0.44 + 0.04.
This is the best time for administration of surrogate HCG. A marked increase in peak systolic velocity with a relatively constant RI of 0.44 + 0.04 in the proliferative phase and starts decreasing as ovulation approaches. It starts to fall a day before ovulation and the lowest value of 0.84 + 0.04 is seen on the day 18 of the menstrual cycle that is around the time of the implantation window.
 
Luteal Phase Changes in Ovarian Vascularity
The functional capacity of the corpus luteum is assessed by the low impedance flow and the abundance of vessels arounds it mature corpus luteum is a highly vascularized structure with a low RI of 0.44 + 0.04. In patients with corpus luteum deficiency the vascularity is not optimal and the RI is raised to around 0.59, with decreased diastolic flow. If pregnancy occurs then low RI of 0.50 continues.24
 
Secretory Changes in the Endometrium
Michael Applebaum in his study with transvaginal color doppler divided the endometrium and periendometrial areas into 4 zones. In the study conducted by him no pregnancy was reported in IVF patients unless vascularity was demonstrated in Zone III or with in Zone III or IV prior to transfer.
 
Doppler Assessment of Uterine and Ovarian Flow in Infertility and IVF
Goswamy found absent diastolic flow in infertility patients and with severe problems and even reversal of diastolic flow.
 
ROLE OF TRANSVAGINAL COLOR DOPPLER IN OTHER CONDITIONS ASSOCIATED WITH INFERTILITY
 
Luteinized Unruptured Follicle
This condition is recognized by serial ultrasonography to monitor the growth of follicle, with failure to see expected changes at the time of ovulation.
The typical blood flow pattern seen in the corpus luteum is absent.
 
Luteal Phase Defect
This is due to decreased vascularization of corpus luteum. The three to seven fold increase in blood supply is necessary to deliver, the steroid precursors to ovary and removal of progestrone as shown in experimental animals.
An increasing corpus luteum resistance index indicates less chances of embryo survival specially within first 8 weeks of pregnancy.
 
Fibroid
To define the borders of fibroid color Doppler is of real help as the vascular supply at the periphery of 25the leiomyoma can be dilineated very well. Good vascularity denotes a favourable response to GnRH if used before laparoscopic surgery.
 
Endometriosis
On gray scale scan endometrioma is seen as a homogeneously echogenic intraovarian mass. Color doppler may demonstrate flow around and not in the cyst.
 
Tubal Causes
During active phase of PID low impedance blood flow signals are usually detected and after effective antibiotic therapy flow tends to return to normal. In the absence of this change surgery is indicated.
 
Polycystic Ovarian Disease (PCOD)
Contrary to the normal ovarian blood flow, which is seen around the growing follicle, PCOD subjects show abundantly vascularized stroma. Waveforms obtained from the ovarian tissue showed a mean resistance index of 0.54 without cyclical change between repeated examinations.
 
Uterine Factor
The possibility of decreased uterine blood flow may be associated with infertility as already discussed in proceeding paragraphs. Goswamy depicted in their study that uterine artery indices which were high in failed IVF cases improved after the patients were put on oral estrogen therapy and pregnancy rate improved when compared to those who did not get this treatment.
 
Color Doppler and its Contribution Towards in Vitro Fertilization
During stimulation protocols color doppler ultrasound has its greatest contribution in monitoring follicular 26development and guiding oocyte harvesting procedures. The use of color doppler ultrasound can occasionally be of help as it avoids accidental puncture of iliac vessels and also vessels on the surface of ovary.
 
Avoidance of Ovarian Hyperstimulation Syndrome (OHSS)
In a stimulated cycle resistance of the intraovarian vessels measured by transvaginal color doppler correlates well with number of follicles, that is those with more than 15 mm size. This correlation exists even during the early follicular phase, when follicular recruitment and development have just started. This suggest that vascularization of the follicles may play a role in their maturation from early follicular phase onwards. This study in the early follicular phase can prevent OHSS.
 
Optimal Conditions for Embryo Transfer
As shown in a recent work by Campbell it is possible to calculate the probability of pregnancy by using PI values of uterine artery on the day of embryo transfer. Highest probability of pregnancy was predicted for patients who had medium values for PI. Those with high PI had failure rate upto 35%. In other words the lower the PI value more the chance of pregnancy. Steer et. al. have shown that if P.I. is > 3 before E.T. no pregnancy results. (NM)27
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Dr Narendra Malhotra
  • President FOGSI (2008) Senior Vice President of FOGSI (2003)
  • Dean Elect of I.C.M.U(2007)Vice Dean Indian College of Medical Ultrasound (2006)
  • Director Ian Donald School of Ultrasound FOGSI Imaging Science Chairman (1996–2000)
  • National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course
  • Awarded best paper and poster at FOGSI:5 times, Ethicon fellowship, AOFOG young gyn.award, Corion award, Man of the year award, Best Citizens of India award
  • Editor 8 books, many chapters, on editorial board of many journals
  • Revising editor for Jeffcoate's Textbook of Gynaecology (2007)
  • Very active Sports man, Rotarian and Social worker
Malhotra Nursing and Maternity Home Pvt. Ltd.
84, M.G. Road, Agra-282 010
Phone: (O) 0562-2260275/2260276/2260277 (R) 0562-2260279, (M) 98370-33335;
Fax: 0562-2265194
Apollo Pankaj Hospitals, Agra
Co-ordinator Deptt. Obs and Gyn28
 
Editors Comment
Dr Narendra Malhotra, a totally commited person towards the profession, has exceptional knowledge of Sonography and Color Doppler. His organizational skill is unparallel, his longterm foresight on scientific advances is put into implementation. He is an excellent person to work along, leadership quality are marvelous. He is devoted to his family knows how to give due respect to elders and looks forward to take the Generation Next to greater heights.29
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Dr Chaitanya Nagori
  • Director of Dr. Nagori's Institute for Infertility and IVF, Ahmedbad and doing exclusively infertility practice since last 17 years.
  • Very popular teacher and a perfect academician
  • Training of infertility and ART from experts of Singapore and Bourn-Hallam Clinic, London
  • Trained in 4D USG at Vienna, Austria
  • Trained for fetal echocardiography from Berlin Germany.
Address: Dr CB Nagori
Dr Nagori's Institute for Infertility and IVF,
2nd Floor, ‘Kedar’, Opp. Krupa Petrol Pump,
Near Parimal Garden, Ahmedabad. 380006
Telephone No: 079-26401090, 26402090, 26403090
 
Editors Comment
Dr. Chaitanya Nagori, is an excellent teacher, with phenomenal knowledge of Sonography 2D, 3D, 4D and Color Doppler specially in context with ART. He lives life at his own terms with friends, encourages juniors and loves music. A typical scientific person enjoys work.30
Q 14: How much useful is 3D, 4D US in diagnosis of uterine anomalies?(CN SP)
3D 4D US is known as virtual hysteroscopy.
Ultrasound
Senstitivity
Specificity
• TVS
95.21
92.21%
• TVCD PD
99.29%
97. 23%
• Volume USG
98.38%
100%
• Sonohysterography
98.18%
100%
Richman TS et al, Radiology 1984
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1. Unicornuate, 2. Bicornuate, 3. Septate, 4. Subseptate, 5. Arcuate., 6. Hypoplastic
Q 15: How can septate uterus be differentiated from bicornuate uterus?
It was believed that septum does not show vascularity, but studies have proved that at least 71% of septae show vascularity, but the flow has a higher resistance (RI 0.68–1.00) than the normal myometrium (0.58–0.84). On Coronal view on 3D USG, fundal dimple is a sign of bicornuate uterus. Same view shows biconvex shape of the endometrial cavities in bicornuate uterus as compared to flattened medial surface in septate uterus.31
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Septate uterus
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Bicornuate uterus
On 3D US and even on 2D US with a high resolution equipment, a myometrial layer dipping in between the endometrial cavities can be seen in bicornuate uterus.(CN SP)
Q 16: How will colour Doppler help in differentiation of various endometrial lesions when 2D US shows focal endometrial thickening?(CN SP)
On colour Doppler polyp shows a single feeding vessel in the pedicle. Adhesions are not vascular. Hyperplastic endometrium shows multiple vessels entering into the thickened endometrium. Any lesion when benign shows moderate to high resistance vascularity. Atypia always shows decreasing resistance. 32
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Endo. Hyperplasia
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Vesicular mole
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Polyp
33
Q 17: How will 3D, 4D (Volume) US help in differential diagnosis of endometrial lesions? (CN SP)
3D, 4D US because of its coronal view is diagnostic for endometrial lesions.
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1. Polyp 2. Synechiae
Q 18: Will any additional procedure help with volume US for diagnosis of endometrial lesions?(CN SP)
Sonohysterography can be used with 3D US for diagnosis of endometrial lesions. It also helps for assessment of the endometrial cavity capacity in cases of synechiae.
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Polyp on sonohysterography
34
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Polyp on sonohysterography
Q 19: Is colour Doppler useful for tubal evaluation? (CN SP)
Sonohysterography can be extended to sonosalpingography. This procedure shows patency of tubes and can replace second look laparoscopy. Apart from tubal patency, salpingitis is a pure colour Doppler diagnosis. In cases of unexplained infertility especially if adnexa is thickened and colour Doppler shows low resistance vascularity it is a suggestion of salpingitis.
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Salpingitis
35
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Sonosalpingography
Q 20: Does Colour Doppler help in diagnosis of Polycystic ovaries ?(CN SP)
Features of polycystic ovaries: On 2D US:
  • Enlarged spherical ovaries > 10 cc
  • 12 / more immature follicles (2–9 mm)
  • Predominant hyperechoic stroma 3D
  • At least six atretic follicles
  • Peripheral and general cystic pattern
  • Ovarian area: 5.3 cm2 (93% sensitivity and 91% specificity) – strict longitudinal ovarian section
  • Stromal area: 4.6 cm2 (91 % sensitivity and 86% specificity)
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    Polycystic ovary
    36
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    Stromal flow
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    Uterine art flow
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    3D volume
    37
  • Ovarian volume 6.6 cc (91 % sensitivity and 91% specificity)
    On colour Doppler: Constant vascular resistance in ovaries no cyclical changes –anovulation: RI: 0.54 + 0.04(0.78 + 0.06)
  • PI: 0.89 + 0.04(1.87 + 0.38) PSV: 11.9 + 3.2 (9.6 + 2.1)
Q 21: What findings are seen in low reserve ovaries and poor responding ovaries?(CN SP)
Poor responding ovary: resistance to response and requires higher doses for stimulation Intra ov. RI > 0.68 Intra ov. PSV < 5 Uterine art. RI > 0.79
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Poor responding ovary: ovarian and uterine flow
38
Low reserve ovary: (an ovary which has lower reserve capacity, i.e. less number of antral follicles in reserve)
Small sized ovaries (< 2 cms, < 3 cc). < 3 antral follicles
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Low reserve ovary
Q 22: What are ultrasound markers of ovarian reserve? (CN SP)
  • Number of antral follicles
  • Ovarian stromal FI
  • Total ovarian stromal area
  • Total ovarian volume
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Antral follicle count
39
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Stromal and ovarian volume
Q 23: What are the findings of a mature fertilizable ovum? (CN SP)
Features of mature fertilizable ovum:
On 2D US: Follicle of at least 16 mm size.
On colour Doppler:
Vascularity covering at least 3/4th circumference of the follicle.
On pulse Doppler:
RI of 0.4 – 0.48, and PSV of > 10 cm/sec.
On 3D US follicular volume of 3–7 cc
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40
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2D, colour Doppler, volume and 3 D power Doppler of follicle
41
Presence of cumulus
On 3D power Doppler: VI: > 6, FI: > 35, VFI: 3–5 (these studies are based on the findings of our study of 500 cases, published at ISUOG 2006, London.) It has been seen that when 2D and colour Doppler parameters are normal, addition of these parameters can reduce the span of unexplained infertility and increase the success rate of IUI/IVF cycles.
Q 24: What are the findings of an endometrium which is good for implantation?(CN SP)
Features of mature endometrium:
On 2D US:
Endometrial thickness of 6 – 8 mm
Multilayered endometrial pattern – grade A / B endometrium
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42
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43
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2D, colour Doppler, volume and 3D power Doppler of endometrium
On colour Doppler:
Vascularity reaching zone 3–4 of endometrium
On pulse Doppler: RI 0.5–0.6, and PI: 1.1–2.3.
On 3D US:
Endometrial volume 3–7 cc,
On 3D power Doppler: endometrial VI:30–70, FI: > 20, VFI: > 5. (these studies are based on the findings of our study of 500 cases, published at ISUOG 2006, London.)
Q 25: When should embryo transfer or IUI be withheld?(CN SP)
Pre hCG uterine artery evaluation plays an important role in decision making of embryo transfer. Embryo transfer must not be done when pre hCG uterine artery PI is > 3.2, endometrial thickness is < 6 mm and when the endometrial vascularity does not reach zone 3–4.44
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Uterine artery flow
Q 26: Can luteal phase abnormalities be diagnosed by ultrasound ?(CN SP)
Normal luteal phase is diagnosed by colour Doppler of corpus luteum, endometrium and uterine artery.
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45
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Midluteal corpus luteal and endometrial flow
For midluteal phase corpus luteum
  • RI 0.35–0.50
  • PI 0.70–0.80
  • PSV 10–15 cm/sec
For midluteal phase uterus and endometrium
  • Spiral artery RI 0.48–0.52
  • Uterine Art. PI 2.0–2.5
  • Uterine Art. PSV 15–20 cms/sec
 
Luteinized Unruptured Follicle
When seen on 2D US in mid luteal phase corpus luteum and LUF have similar appearance. On colour Doppler in LUF, Perifollicular RI 0.51–0.59 is seen and through out the cycle remains almost constant with bilateral similar values. Endometrium may appear normal for the luteal phase or may be thin and show high resistance vascularity.46
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LUF
Luteal phase defect: Corpus luteal flow
Normal
LPD
Perifollicular
0.56 + 0.06
0.58 + 0.04
LH peak day
0.44 + 0.04
0.58 + 0.04
Midluteal phase
0.42 + 0.06
0.58 + 0.04
Late luteal phase
0.50 + 0.04
0.58 + 0.04
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LPD, corpus luteal and endometrial flow
Spiral artery flow:
Phase
Control RI
LPD RI
Periovulatory
0.53 +0.04
0.70 +0.06
Mid luteal
0.50 +0.02
0.72 +0.06
Late luteal
0.51 +0.04
0.72 +0.04
47
 
LAPAROSCOPY, HYSTEROSCOPY, MICROLAPAROSCOPY AND D AND C – TODAY IN INFERTILITY ASSESSMENT
Q 27: Hysteroscopy is it underutilized? (ST)
Hysteroscopy should not be considered as a routine investigation in the infertile couple.
(RCOG Guidelines: Grade C Recommendation 1999)
But as we all know hysteroscopy remains the gold standard for uterine cavity assessment. It is mandatory to perform hysteroscopy whenever laparoscopy is performed for evaluation of an infertile woman.
It is an important tool in investigation of subfertile woman in the following situations.
  • An intrauterine lesions suspected on TVS /HSG
  • Relatively high-risk of intrauterine adhesions as in instrumental interventions in the past (D and C), history of endometritis, recurrent miscarriage
  • Failure of implantation of good embryos following consecutive IVF cycles.
Q 28: Is hysteroscopy must pre-ART? (ST)
Though we know that transvaginal sonography is an excellent tool to diagnose uterine pathologies, we believe in performing pilot office hysteroscopy prior to ART as a routine in order to enhance the clinical pregnancy rates, as all intrauterine pathologies cannot be diagnosed accurately on transvaginal sonography.
Patients with recurrent IVF embryo transfer failures after normal hysterosalpingography findings should always be reevaluated using hysteroscopy prior to further commencing IVF-embryo transfer cycle.
As we say that transvaginal sonography is an extension of per vaginal examination, we believe that office hysteroscopy as an extension of transvaginal sonography. Being an OPD procedure, it is completed in just few minutes. Few pathologies like small polyps/intrauterine band of adhesions (which might have 48been missed on TVS) can easily be diagnosed and tackled by bipolar/monopolar energy in the same sitting. It also guides us about the curvature of the utero cervical canal, which helps in the embryo transfer procedure subsequently. It also helps us to tackle a tightly closed internal os or flimsy adhesions at the internal os before embryo transfer than at the time of embryo transfer.
 
GENITAL KOCH'S AND INFERTILITY
Q 29: What is the prevalence of genital tuberculosis and infertility? (AM)
The prevalence of genital tuberculosis differs in different population groups, geographical area (urban/rural areas) and the technique used to diagnose tuberculosis. The incidence of mycobacterium tuberculosis varies from 1 to 16% over the globe being lowest in developed countries. In India the prevalence is 5 to 15%. However it is pertinent to treat women with actively replicating mycobacteria rather than treating dormant disease also picked up by the new ultrasensitive tests. Early confirmation of the diagnosis of tuberculosis is a challenging problem specially in case of paucibacillary and extra-pulmonary forms.
Diagnosis of tuberculosis is mainly based on clinical features, tuberculin test, ESR estimation, quantiferon gold test, radiological examination and other methods such as histopathology and/or demonstration of acid fast bacilli (AFB) and isolation of mycobacterium tuberculosis from the clinical specimens. These techniques have limitations of speed, sensitivity and specificity. Accurate identification of mycobacterium tuberculosis through culture is presently the yardstick and gold standard for diagnosis, but the time required and frequent negative results in paucibacillary specimens are important limitations49
  • During the last two decades several rapid techniques for detection of early growth (5–14 days as compared to 2–8 weeks with conventional methods) have been described which can help in obtaining the culture and sensitivity reports relatively early. Prominent among such methods are BACTEC (5–10 days), mycobacterial growth indicator tuber (MGIT) (7–12 days), and Septi-chek, MB / BacT systems.
  • A variety of PCR methods have been developed for detection of specific sequences of M. tuberculosis and other mycobacteria. These PCR assays may target either DNA or rRNA/and these could be based on conventional DNA based PCR, nested PCR and RT-PCR. Out of the DNA probes and ribosomal RNA sequencing probes rRNA targeting probes are 10–100 fold more sensitive than DNA targeting and may be used to confirm the diagnosis directly in the clinical specimens in a good proportion of cases; the lowest detection limit is around 100 organisms. At present these are useful mainly for rapid identification of mycobacterial isolates.
  • Gene amplification methods for direct detection of M. tuberculosis sequences from clinical specimens have made a major impact on the diagnosis of mycobacterial diseases. Gene amplification techniques are highly sensitive and under optimum conditions may detect 1–10 organisms. These gene probes, gene amplification methods and in situ approaches offer unparalleled capability to enhance the diagnosis of tuberculosis in near future.
    50
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Dr Nalini Mahajan
Director: Mother and Child Hospital and IVF ~ICSI Centre, New Delhi
Address of correspondence:
Mother and Child Hospital
D-59, Defence Colony, New Delhi – 23
Telephone Nos.: 011-24631175 / 24656736
Fax Nos.: 011-26256803 / 24621727
  • Gold Medal for standing first in 10th Board examination, J&K University
  • President's Gold Medal for standing first in MBBS, Delhi University
  • Honors in Masters at UK
  • Best Paper presentation Embryology – ‘Culture of Zona Free Nlastocyst’ ISAR 99.
  • Best paper presentation for ‘Ultrasound Guided Hysteroscopy’ IFS 2005
 
Editor's Comment
Dr Nalini Mahajan, a dedicated consultant specialized in Infertility IVF~ ICSI and also factors which leads to difficulty in conceiving or continuing pregnancy. She has a brilliant career starting from North India reaching UK and back to Delhi. She never lets others realise her authority, excellence to any body. She will do work quietly with no expectations of appreciation. As a person she is a good friend concerned about juniors and enlighten there career with making them think.51
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Dr Sunita Tandulwadkar
md fics ficog dip in endo (usa and germany)
  • Chief, Ruby Hall IVF and Endoscopy Center, Ruby Hall Clinic, Pune
  • Head of the department of Ob and Gyn. Ruby Hall Clinic, Pune
  • Gynae Endoscopist: Poona Hospital and Research Center, Pune
  • National Coordinator: FOGSI Endoscopy- Infertility Committee
  • Started the trend of advanced endoscopic surgeries in the city of Pune
 
Editors Comment
Dr Sunita Tandulwadkar, is an excellent Laparoscopic surgeon with deep knowledge of ART. She has conducted many workshops and events. She has good qualities to get the work done for the Corporate Excecutive Senior Gynaecologists and effectively from Juniors. Her zeal to excl keeps her ahead of many. She deserves a higher platform in FOGSI to so her Endoscopic skills with leadership qualities.52
 
Tubercular Endometritis: (Nalini)
Q 30: Are we justified in starting ATT on the basis of a positive DNA PCR (EB) alone – with no other obvious clinical or laparoscopic finding?
Based on a study that we conducted at our centre we concluded that it is important to treat TB on the basis of a positive molecular test. The treatment should be for 6 months. With an intensive course of four drugs for the first 2 months and then two drugs for 4mths. EB can be repeated after 3–4 months of treatment
 
Study at MCH
Patients with TB DNA PCR positive (57) divided into two groups
Tubes normal on laparoscopy – clean pelvis:
38
Tubes abnormal on laparoscopy -
19
Tubes normal – DNA PCR positive divided into two groups
Group A: ATT given
19
  • Spontaneous Conceptions
  • IUI pregnancies
  • IVF pregnancies
  • Total
  • 6 (31%)
  • 0
  • 4 (4/13 – 30.7%)
  • 10(52.6%)
Group B: ATT not given
19
  • Spontaneous conceptions
  • IUI Pregnancies
  • IVF
  • 0
  • 0
  • 8 (42.1%)
Even though the overall pregnancy rate in the two groups is similar there were no spontaneous pregnancies in the untreated group. This would indicate a problem at the level of the tubal epithelium,
Q 31: If the EB for TB DNA-PCR is positive after a complete course of treatment should you carry on with second line drugs or go ahead with ART? (Nalini)
Again based on a study we conducted we felt that there was no justification in giving second line TB drugs without a positive culture sensitivity report.53
79 patients who had repeat endometrial biopsy-DNA PCR positive after treatment were followed up and went ahead with their infertility treatment.
  • 19 pts lost to follow up
    N=60
  • 13 spontaneous conceptions (21.6%)
    • 1 ectopic pregnancy, 1missed abortion.
    • 11 delivered.
  • 11 IUI
    • 7 negative
    • 4 pregnant (36.3%/)- delivered.
  • 36 IVF
    • 13 negative.
    • 23 positive (63.8%)
  • 4 abortion (17.3%)
  • 19 delivered (52.7%).
Q 32: Is there an association with endometriosis? (Nalini)
Of 62 patients of endometriosis diagnosed on laparoscopy at our centre 34 (>50%) DNA PCR TB positive. It is well known that in endometriosis also there is modulation of the immune system.
Q 33: Genital Koch's and ART—Results? (KR)
Recommended test to confirm the diagnosis of suspected case of genital Koch's
  1. Tuberculin skin test: sensitivity of only 55% and a specificity of 80% in patients with genital tuberculosis. False positive reactions may occur with non tuberculous mycobacterial infection. False negative reactions occur in a frequency of approximately 20% of patients with known active tuberculosis.
  2. Chest X ray: may help as corroboratory evidence to detect pulmonary TB, most often it's normal.
  3. Suspected lesions on the external genital area should be biopsied, histology typically demonstrates caseous granulomatous lesions with giant epithelioid cells
    54
  4. Culture on solid media gives a definitive testing for Mycobacterium Tuberculosis B, the main disadvantage being time taken for the test (approximately 4 weeks) and sensitivity is low.
  5. Liquid culture with radiometric growth detection such as BACTEC-460 or non-radiometric (CO2 growth detection such as BacTAlert 3D, provides more rapid results (avg- 10–14 days)
  6. DNA and RNA PCR: have revolutionized testing for tuberculosis. They are highly sensitive tests capable of detecting MTB with even less than 10 bacilli in the sample. DNA PCR is a rapid, highly sensitive test, but may give false positive result and cannot differentiate between MTB and MOTT, where as RNA PCR in addition to being highly sensitive can differentiate MTB and MOTT, it has been approved by the FDA for tubercular testing.
Patients with diagnosed mycobacterial infection should receive a course of antitubercular treatment. Followed by retesting to make sure the cure of infection. It is worthwhile to counsel the couple for an IVF and ET, failure to conceive even after IVF is a possibility when one may have resort to surrogacy.
 
MALE FACTOR
Q 34: What is the present scenario of infertile male? (RS)
Male sub-fertility is on the rise and contributes partly or wholly to more than half the cases of infertility. The reasons for this are many including increasing environmental toxins which act as endocrine disruptures, and high stress levels. Additionally, however, more cases are also being diagnosed because men are more willing now to get themselves tested.
Q 35: Varicocele surgery is it over-rated?(RS)
Varicocele surgery is controversial. The standard textbook of urology – Campbell's Urology – calls 55varicocele the “ most common correctable cause of male infeetility.” On the other hand, the Cochrane database review concludes that varicocele surgery does not improve pregnancy rates.
The truth probably lies in between – some patients definitely benefit from varicocele surgery showing a dramatic improvement in semen quality and producing a pregnancy, while others have no benefit at all. Hence, it is valid to suggest surgery for a clinical varicocele (there is no point in looking for sub-clinical varicoceles on ultrasound), before proceeding to ART, if an adequate trail of conservative therapy has not helped. Microsurgical ligation of the varicocele should be done. Laparoscopic ligation has a high recurrence rate.
Q 36: In an Infertile couple ~ What's the incidence of Azoospermia? (RS) Vas deferens/Seminal vesicles causes? Immunological causes? Sperm Dysfunction? Abnormal Semen Quality?
Approximately 10% of male infertility is due to azoospermia. About 90% of azoospermia is due to testicular failure and the rest is due to obstruction. The commonest cause of obstruction is a block in the epididymis or congenital absence of the vasa deferentia. Vasal blocks are usually iatrogenic (following vasectomy or hernia surgery). Obstruction at the level of the seminal vesicles or ejaculatory ducts is relatively uncommon and is characterized by low volume of ejaculate and absence of fructose in the semen.
Immunological cause are less common than thought earlier, and the diagnosis is difficult since most laboratories test for antibodies using a ELISA method which is highly unreliable.
Isolated sperm defects in the form of total asthenozoospermia, necrozoospermia, or extreme teratozoospermia are uncommon and usually can be treated only by ICSI.56
Q 37: Male Infertility – Antioxidants Vit.E, C, Zinc, CoQ, –true role and opinion on Empiric use of antibiotics in IUI, IVF, ICSI ? (RS)
There is no drug which had been proven to be consistently effective in well-controlled studies. A few men with inadequate bioactivity of the gonadotropins will respond to hormonal therapy. The rest of the therapies are empirical. Since there is strong experimental evidence to suggest and excessive ROS is bad for the sperm there appears to be some role for the various preparations that contain anti-oxidants. Injectable testosterone should not be used as it can cause suppression of spermatogenesis.
Most studies have shown no role for empirical antibiotics prior to IUI or IVF.
Q 38: Which medications, drugs, habits can reduce sperm count / motility ? Does scrotal cooling Improve sperm count/motility ? (RS)
Sulphasalazopyrine, nitrofurantoin, spironolactone, estrogens, and anti-androgens are medications that can affect sperm count. Recreational drugs like marijuana and other opioid derivatives affect sperm quality. Habits that expose the man to excessive heat can affect semen –e.g. frequent use of sauna or steam, very hot baths, or tight underwear. Excessive smoking can affect sperm chromatin integrity. High levels of stress can also affect sperm quality.
Scrotal cooling has been reported to be useful in men who work in a hot environment or who have a varicocele. Routine use of scrotal cooling for all men with oligozoospermia has not been proven to be useful.
Q 39: What's the success rate of IUI in oligospermia and normal sperm count? (RS)
IUI is not a very efficient treatment for pure male factor infertility. The pregnancy rate per cycle is about 8–10% and the cumulative pregnancy rate over 4 cycles is 16–25%, that too provided at least one million active sperm can be recovered in the sperm harvest.57
The best results with IUI are in cases of normal semen with cervical hostility or antibodies, where a cumulative pregnancy rate of 40% can be expected. IUI for ejaculatory dysfunction, where the semen quality is usually normal, also has a very high success rate.58
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Dr Rupin Shah
ms mch (urology)
Consultant Andrologist and Microsurgeon
Lilavati Hospital and Research Centre, Mumbai
 
Major contributions to infertility in India
  1. Reconstructive microsurgery: First urologist in India to be trained in male infertility microsurgery; largest experience in the country in microsurgical reconstruction for obstructive azoospermia.
  2. Sperm retrieval for ART: Pioneered new methods of sperm retrieval from the epididymis and testis; largest experience in the country
  3. Management of Ejaculatory Dysfunctions: Pioneered the use of vibrator and electro-ejaculator to treat anejaculation; developed new techniques for treating ejaculatory duct obstruction.
  4. Penile Prosthesis and Erectile Dysfunction. Developed India's first penile prosthesis; pioneered the use of intra-penile injections to treat unconsummated marriages leading to infertility.
  5. Training Workshops: Has conducted numerous training workshops in Andrology which have been attended by over a 1000 urologists and surgeons.
Hospital: 022-26421111
Clinic: (1–8 pm) 022-26616101
Fax on demand: 022-26614821 Mobile: 9321027276
Address for correspondence: Dr Rupin Shah Lilavati Hospital Bandra Mumbai 400050.59
 
Editors Comment
Dr Rupin Shah, is a true genius who has place male infertility treatment to a deserved
International standards in India. He is a phenomenal witty orator who can sparkle any podium or dais. He encourages his followers and likes to see them establish. Inspite of his scientific briallance he maintains a simple unassuming profile. A role model and an excellent friend to have in todays time.60
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Dr Jaideep Malhotra
  • Chairperson International Academic Exchange Committee FOGSI
  • Practicing IVF specialist at Agra (Special Interest in Infertility, Laparoscopy, Ultrasound and Genetics)
  • Member and Fellow of many Indian and International organization
  • Indumati Zhaveri Award, Jagdeshwari Misra Award three times, Ethicon Fellowship, Corion Award original research “Improving endometrial receptivity and blood flows.”
  • Editor of “Fetus Our Other Patient”
  • Credited with producing firsts of U.P.: IVF birth, ICSI birth, IVF Twins, ICSI Twins, IVF Triplets, TESA-ICSI Pregnancy etc. Credited for producing first Test Tube Baby of Nepal
  • Very active social worker and sports woman
Malhotra Nursing and Maternity Home Pvt. Ltd.
84, MG Road, Agra-282 010
Phone: (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98970-33335
Fax: 0562-2265194
Apollo Pankaj Hospitals, Agra CHIEF IVF UNIT 61
 
Editors Comment
Dr. Jaideep Malhotra, is a dynamic lady full of energy and enthusiasm. She has excellent knowledge of ART, Sonography and Color Doppler. Her organizational skills, time management keen interest in scientific advances is put into implementation. She is a lady with great potential with application and goal oriented. She is devoted to his family knows how to give due respect to elders and looks forward to take the Generation Next to greater heights.