infertility centre delhi

Things to know before considering Infertility Management

With the advancement of science and technology and investigations, you may find clues and answers to most of your problems. In this day and age, due to a stressful lifestyle, a problem that some of the couples face is Infertility.

Before opting for the process it is imperative that you gather as much information and knowledge about it.

So here is a list of seven pointers that you must know before going for infertility treatment
To know more please visit www.parentsoffertility.com

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Comparison of clinical features and health manifestations in lean vs. obese Indian women with polycystic ovarian syndrome

ABSTRACT

AIMS: To study the prevalence of clinical manifestations in obese and lean polycystic ovarian syndrome (PCOS) women and their health hazards. SETTINGS AND DESIGN: This prospective study was carried out in a tertiary care infertility clinic from 1.7.2005 till 31.12.2007. MATERIALS AND METHODS: These women were diagnosed to have PCOS by the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine, Rotterdam 2003 criteria. They were further divided into two groups according to their body mass index (BMI): Group A (n = 300), overweight and obese with BMI >23 and Group B (n = 150), normal weight and lean with BMI ≤23. STASTICAL ANALYSIS AND RESULTS: The prevalence of menstrual irregularities [79.2% vs. 44%, P= 0.000, 95% confidence interval (CI) = 0.26ñ0.44)] and clinical hyperandrogenism (74.2% vs. 50.6%, P= 0.000, 95% CI=0.14ñ0.32) was signifi cantly higher in the obese group, whereas android central obesity (waist to hip ratio >0.85) was similar in both groups, irrespective of body weight (47.7% vs. 38%, P= 0.056, 95% CI=0.06 to +0.18). Comparative data of various health manifestations in lean vs. obese women with POCS [Table 4]. Of the health risk manifestations, hypertension occurred in both groups with a similar frequency (41% vs. 35.5%, P= 0.261, 95% CI=0.03 to +0.15). Group A showed an increased prevalence of IGT (25% vs. 10%, P= 0.000, 95% CI= 0.13ñ0.29) and type two diabetes mellitus (11.7% vs. 6%, P= 0.000, 95% CI= 0.13ñ0.29) as compared with group B. endometrial hyperplasia (EH) also showed an increase prevalence in Group A compared with Group B (5.6% vs. 2%, P= 0.055, 95% CI= 0.01ñ0.08), although not statistically significant. CONCLUSION: PCOS emerges as a clinically heterogeneous condition with increased prevalence of health risks such as hypertension, diabetes and EH. Of these, diabetes and EH appear to be more prevalent in the obese, putting them at a greater risk of morbid problems at a much younger age than the lean ones.

INTRODUCTION

Polycystic ovarian syndrome (PCOS) aff ects four to 12% women of reproductive age.[1] In 1935, Stein and Leventhal fi rst described the association of polycystic ovaries, amenorrhea, hirsutism, and obesity. The key features necessary for the diagnosis of PCOS were detailed at a conference convened by the National Institute of Health in 1990 and they were menstrual dysfunction and hyperandrogenism, with exclusion of other causes of hyperandrogenism (congenital adrenal hyperplasia, androgen-secreting tumors, and hyperprolactinemia). Probable criteria included perimenarchal onset, insulin resistance, elevated leutenizing hormone to follicle-stimulating hormone ratio and polycystic ovaries by ultrasonography (USG). PCOS was redefi ned at a joint consensus meeting of the European Society of Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM), held in Rott erdam in May 2003. This included the presence of two of the following three criteria: (a) oligo and/or anovulation, (b) polycystic ovaries on USG and (c) hyperandrogenism (clinical and/or biochemical), with the exclusion of other etiologies. The morphology of the polycystic ovary has been redefi ned as an ovary with 12 or more follicles measuring 2ñ9 mm in diameter and/or increased ovarian volume (more than 10 cm3 ).[2]

Recent insights into the pathophysiology of PCOS have shown that insulin resistance is a key feature and predisposes to type two diabetes mellitus in the long run. Higher levels of plasminogen activator inhibitor (PAI) type one, decreased vascular relaxation and endothelial dysfunction.

result in increased risk of hypertension and coronary artery disease. Chronic anovulation leads to a higher risk of developing endometrial hyperplasias (EHs), with or without cytological atypia as a sequel to unopposed estrogen exposure in the absence of progesterone.[1]

The aim of this study was to study the prevalence of clinical manifestations and health risks in obese and lean PCOS women; primarily, impaired glucose tolerance (IGT) and diabetes, menstrual irregularity, and clinical hyperandrogenism and, secondarily, EH, android obesity and hypertension.

Impact of gonadotropin‑releasing hormone antagonist addition on pregnancy rates in gonadotropin‑stimulated intrauterine insemination cycles

ABSTRACT
OBJECTIVES: The objective of the study is to evaluate the efficacy of gonadotropin releasing hormone (GnRH) antagonist in improving clinical pregnancy rate in gonadotropin stimulated intrauterine insemination (IUI) cycles in patients of unexplained infertility. STUDY DESIGN: This was a prospective, randomized case–controlled study. SETTINGS: The study was conducted in the infertility clinic of a tertiary care center. MATERIALS AND METHODS: Four hundred twenty seven women undergoing IUI following controlled ovarian stimulation with gonadotropins (recombinant follicle stimulating hormone [r FSH] 75 IU/day) were randomly divided into two groups. Women in Group I received GnRH antagonist (Cetrorelix 0.25 mg/day) in a multiple dose flexible protocol. Women in Group II received r FSH alone. Ovulatory trigger was given with human chorionic gonadotropin 5000 IU when dominant follicle was ≥18 mm. IUI was performed within 44–48 h. Both groups received similar luteal phase support. Primary outcome measure was clinical pregnancy rate. The trial was powered to detect an absolute increase in clinical pregnancy rate by 13% from an assumed 20% clinical pregnancy rate in the control group, with an alpha error level of 0.05 and a beta error level of 0.20. RESULTS: Clinical pregnancy rate in Groups I and II was 27.6% (n = 56) and 26.5% (n = 54), respectively (P=0.800). Ongoing pregnancy and multiple pregnancy rates were likewise similar between the groups. CONCLUSIONS: Addition of GnRH antagonist to gonadotropin stimulated IUI cycles results in no significant difference in clinical pregnancy rate.

INTRODUCTION

Unexplained infertility contributes to about 10–30% of subfertility, depending on diagnostic criteria. Intrauterine insemination (IUI) combined with controlled ovarian stimulation (COS) has been established as a first-line treatment for couples with unexplained infertility. The rationale of COS and IUI is to increase the number of available female and male gametes at the site of fertilization by achieving two to three dominant follicles, followed by a perfectly timed insemination. The use of IUI with COS in a well selected group of patients with unexplained infertility results in comparable cumulative pregnancy rate when compared to in vitro fertilization (IVF) and hence appears more cost effective.

To increase the chances of success in terms of pregnancy rate in COS IUI cycles, various therapeutic approaches have been tried by various researchers, such as different ovarian stimulation protocols, double insemination, and prevention of premature luteinizing hormone (LH) surge. According to the Cochrane review on ovarian stimulation protocols for IUI in the women with subfertility, use of gonadotropins for COS in IUI results in higher pregnancy rate than clomiphene citrate-stimulated cycles (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.2–2.7). A recent meta-analysis clearly indicated that double insemination does not result in higher clinical pregnancy rate compared with single IUI in couples with unexplained infertility. Double insemination has been suggested by researchers because of the hypothesis that capacitated sperms in the inseminate are active for only 2–3 h, so they may not be able to back up ovulation which takes place in between the next 20 and 24 h. However, it appears that precise timing of insemination in relation to ovulation so as to enable active sperms to reach and fertilize the oocyte should obviate the need for double insemination.

Premature LH surge is defined as the surge that precedes the triggering of ovulation iatrogenically. Prospective data have shown that premature LH surge occurs in almost 23% of COS cycles (95% CI 22–43%), which appears quite significant and can interfere with the optimal timing of the insemination. LH surge can be effectively prevented by administering a gonadotropin releasing hormone (GnRH) agonist or GnRH antagonist. Use of GnRH agonist is not recommended in IUI cycles because of prolonged administration of injections prior to and during stimulation to achieve complete downregulation of GnRH receptors, risk of excessive follicular stimulation, and higher cost and inconvenience to the patient.

On the other hand, GnRH antagonist competitively blocks the GnRH receptors and immediately causes pituitary suppression, thereby reduces LH and follicle-stimulating hormone (FSH) secretion within 2–4 h. The efficacy of GnRH antagonist in prevention of premature LH surge is well-established.[17,18] The inhibitory effect of GnRH antagonist is reversible, dose-dependent and is associated with the equilibrium between endogenous GnRH and GnRH antagonist concentration. Cetrorelix (Cetrotide, EMD Serono) and Ganirelix (Antagon, Organon) are the two GnRH antagonists available for clinical use.
The protocols of GnRH antagonist administration in COS IUI cycles are well defined; however; the flexible regimen is the one which is used commonly in mild stimulation cycles.

Hysteroscopic Guided Biopsy, Polypectomy and Myomectomy

Abha Majumdar, Tejshree Singh
INTRODUCTION

Hysteroscopy is a minimally invasive intervention that can be used to diagnose and treat many intrauterine and endocervical problems. Hysteroscopic polypectomy, myomectomy, and directed endometrial biopsy are just a few of the commonly performed procedures. Given their safety and efficacy, diagnostic and operative hysteroscopy have become standards in gynecologic practice.

SURGICAL ANATOMY
Endometrial Polyps
1. Endometrial polyps are localized overgrowths of the endometrium that project into the uterine cavity. They develop because of excessive multiplication of the endometrial cells, may be hormonally dependent and increase in size depending upon estrogen levels.
2. Polyps may be sessile or pedunculated and rarely include areas of neoplastic growth. Specifically, adenomatous hyperplasia and endometrial adenocarcinomas have been reported in only 0.6% of cases of endometrial polyps.
3. They can usually be detected on an ultrasound scan on second or third post-menstrual day or in mid-cycle, when estrogen levels are maximal, and the endometrium is echogenic.
4. The prevalence of polyps is estimated to be 10 to 24% in hysterectomy samples. Endometrial polyps are rare among women younger than 20 years of age.
5. The incidence of these polyps rises steadily with increasing age, peaks in the fifth decade and then declines after menopause.
Fibroids
1. These are well-circumscribed, non-cancerous tumors arising from the myometrium of the uterus. In addition to smooth muscle, leiomyomas are also composed of extra-cellular matrix, i.e. collagen, proteoglycan, fibronectin.
2. Fibroids are the most common solid pelvic tumors in women, causing symptoms in approximately 25% of reproductive age women. The overall prevalence increases to over 70%, inclusive of asymptomatic fibroids. These are usually detected in women in their 30s and 40s and may shrink after menopause in the absence of post-menopausal estrogen replacement therapy.
3. These are classified by their location in the uterus.
A. Subserosal ones are located just under the uterine serosa and may be pedunculated or sessile.
B. Intramural fibroids are found predominantly within the myometrium but may distort the uterine cavity or cause an irregular external uterine contour.
C. Submucous fibroids are located just under the uterine mucosa and, may be either pedunculated or sessile.
4. Tumors in subserosal and intramural locations comprise the majority (95%) of all leiomyomas; submucous leiomyomas make up the remaining 5%.
5. Although this classification scheme is widely used by clinicians, it suffers from the limitation that few leiomyomas are actually a single “pure” type. Most leiomyomas span more than one anatomic location and, therefore, are hybrids, e.g. a predominantly intramural leiomyomas with a submucous component.
6. Transformation of uterine leiomyomas to uterine leiomyosarcomas is extremely rare, and, in fact, many researchers and clinicians believe this type of transformation never occurs. Uterine leiomyosarcomas are found in approximately 0.1% of women with leiomyomas and are reported to be more frequently associated with large or rapidly growing fibroids.
Thickness of the Uterine Wall
Thickness of the Uterine Wall1 This knowledge allows the surgeon to manipulate the surgery on the basis of the area of the uterus where surgeon is operating. The uterus is longer and thicker in reproductive-aged women than in postmenopausal women.
PREOPERATIVE PREPARATION
Appropriate surgical management always begins with accurate history taking, physical examination, and careful workup of the suspected problem. In preparation for hysteroscopic procedures, the following considerations may be useful.
LAB STUDIES: Apart from general health tests, the following tests are required
• Blood typing and screening: With the risk of hemorrhage approaching 7-8% in some surgical hysteroscopic procedures, a sample in the blood bank increases the efficiency of access to replacement of blood products, if needed.
• Electrolyte determinations: In patients with medical disorders that predispose them to metabolic abnormalities, e.g. diuretic use, electrolytes should be tested preoperatively. Some surgeons routinely obtain baseline levels in case a significant deficit of distention medium occurs especially with a hyposmolar solution, whereas most obtain electrolyte levels intraoperatively or postoperatively only if a clinically significant fluid deficit occurs. The ultimate decision should be based on the type of case, the surgeon’s skill, the suspected fluid absorption, and the ability to accurately ascertain fluid deficits in the operating room.
• Determination of human chorionic gonadotropin (hCG) levels is mandatory in any woman of reproductive age to exclude pregnancy.
• Cervical cultures: May be taken depending on prevalence of Chlamydia and gonorrhea in the population and a wet smear for bacterial vaginosis and trichomoniasis are recommended.
• Papanicolaou test: A normal or abnormal Pap smear that has been appropriately evaluated is required because trauma to the cervix may alter the appearance of any existing abnormalities.
IMAGING STUDIES
• Ultrasound of the lower abdomen is done postmenstrually to evaluate the size and shape of the uterus, endometrial thickness, fibroids (location (Figs 1 and 2), whether distorting the uterine cavity Fig. 3) as well as endometrial polyps (Fig. 4).
• Hysterosalpingogram or sonohysterosalpingogram is used for evaluating the uterine cavity and patency of fallopian tubes. However, to selectively look at the uterine cavity, sonohysterography or saline-infused sonography and 3-D ultrasound appear to have a better predictive value than that of hysterography for determining the location and size of fibroids and endometrial polyps (Fig. 5).
• CT scan or MRI: These are not usually needed unless the findings on ultrasound are inconclusive.
ANTIBIOTIC PROPHYLAXIS
Prophylactic antibiotics are not indicated unless the patient has clinically significant cardiac disease or a history of tubal occlusion due to pelvic inflammatory disease.
DIFFICULTIES
Cervical Stenosis

In patients with known cervical stenosis or tortuous cervical canals, preoperative vaginal or oral misoprostol, or intraoperative vasopressin 1% administered paracervically may be used to assist in cervical dilation.
Large Uterus
A uterus longer than 10 cm makes the case difficult, because the length of the hysteroscope is typically 35 cm and it must traverse the length of the uterus, cervix, and vagina while maintaining a position outside the introitus with enough distance to attach the camera and manipulate the fluid inflow-outflow valves and the surgical instruments. Also, maintaining intrauterine pressures in large cavities is more difficult than with small cavities.

Journal of Fertilization: In Vitro – IVF-Worldwide, Reproductive Medicine, Genetics & Stem Cell Biology

Series of 18 Cases of Clomiphene Resistant Anovulatory Women with Polycystic Ovary Syndrome and Altered Response to FSH Stimulation.

Case Represewntation

We report a case series of 18 such PCOS women selected from 100 CC resistant women undergoing r-FSH stimulation with the purpose of ovulation induction.

All patients presented to the outpatient department where their clinical examination was done by a clinician which included measurement of body weight, height, waist and hip circumferences and blood pressure. Height and weight were measured with subjects in light clothes and without shoes, using a standard apparatus. Weight was measured on a calibrated beam scale. The height and WC were measured to the nearest 0.5 cm with a measuring tape. Waist was measured midway between the lower rib margin and the iliac crest at the end of a gentle expiration. BMI was calculated as the weight in kg divided by the height in meters squared (kg/m2 ).

For biochemical and hormonal measurements, overnight fasting blood samples were taken from each subject. Oral glucose tolerance test was done by drawing blood in EDTA-treated test tubes in fasting status and then after 2 h of ingesting 75 g of glucose, by an enzymatic colorimetric method with hexokinase. Lipid measurements including total cholesterol (TC), triglycerides (TGs) and HDL-C were obtained using commercial assay kits. TGs were assayed using enzymatic colorimetric tests using triglycerides GPO blank. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and serum estradiol were measured by chemiluminescence method by Diasorin, LIAISON, Italy. AMH was measured by chemiluminscene method using Beckmancoulter kit.

All study subject’s follicular growth were monitored by transvaginal ultrasound scans LOGIQ P5GE Healthcare with 6.5 MHz trans-vaginal transducer and all scans were performed and assessed by a single sonographer. Ultrasound was performed till adequate follicular growth was obtained.

In all these CC resistant cases, ovulation induction was started with injection of r-FSH 50/75 IU which was increased by 25 units every 5 to 7 days according to low dose step up protocol. Follicular response was monitored by serum estradiol (E2) levels and ultrasound (USG) follicle monitoring (FM). 18 PCOS were selected from this cohort of women as they showed no ovulatory response in terms of rise in serum E2 levels (at least rise of 30 pg/ml from baseline serum estradiol levels (20-80 pg/ ml) or presence of a follicle of 13 mm or larger, even after 18-25 days of stimulation with incremental doses of r-FSH of up to 150 IU.

These women were labeled as ‘FSH resistant PCOS’ and were further stimulated with high doses of injection hMG (Humog Bharat Serum, India). The starting dose of hMG was 150 units which were subsequently increased to 225 units if there was no response after 6 days in terms of rise in S. E2 and USG evidence for dominant follicle. Surprisingly all patient responded or hyper responded within 10 days of stimulation.

We looked for characteristics common to this subset of PCOS women so that we could possibly identify these FSH resistant PCOS’ in advance and treat them differently from the beginning. Phenotypic, laboratory and ultrasound features were noted. These included age, BMI, waist circumference (WC), oral glucose tolerance test (OGTT), triglyceride (TG) levels, AMH, basal FSH, basal LH, ovarian volume and AFC. All these women has clinical features of hyper-androgenism hence testosterone levels were not tested. Observations were made for this subset of women and all of them had almost equal characteristics in terms of high BMI and WC, very high AMH and high ovarian volume with AFC. Interestingly, no patient was a LH hypersecretor.

Therefore, it appears there exists a definite group of anovulatory PCOS, who appear to be resistant to ovulation induction when treated with small doses of FSH alone for the purpose of ovulation induction. There are 2 possible explanations to this resistance to injection rFSH when given in low doses for the purpose of ovulation induction. Firstly, very high levels of AMH have an inhibitory effect on follicular recruitment under the influence of exogenous FSH. Addition of LH possibly increases follicular sensitivity of granulosa cells by increasing FSH receptors on them so that they could respond to lower doses of FSH which are used for ovulation induction in non IVF cycles. Therefore, it appears addition of LH may help to overcome resistance of follicular recruitment by FSH alone, which is a known possibility in PCOS women with concomitant high levels of AMH. The second explanation for FSH resistance observed could be presence of FSH receptor polymorphism which makes the follicles resistant to lower doses of FSH. To overcome this receptor polymorphism one may require higher doses of FSH to be able to go above the serum threshold levels of FSH required to select dominant follicles. It is well researched that frequency of FSH-R Ser680 variant is high in hypo-responders and consumption of FSH is higher in carriers of this polymorphism. It is also interesting to note that ovarian stimulation for IVF where higher doses of FSH are used at the initiation for controlled ovarian stimulation, may overcome both of these inhibitory effects, whether it is the inhibitory effect of high AMH on follicular growth or the FSH receptor polymorphism.

S. No.
Characterstics
Min
Max
Mean
SD
Normal physiological index
1
BMI (kg/m2)
29
36
33
3.32
18-24.9
2
WC (cm)
98
124
108
5.0
<80
3
AMH (pmol/L)
60
145
106
37.7
7.7-22.5
4
FSH (mIU/ml)
4
8
5.6
1.09
3-10
5
LH (mIU/L)
3.3
12
6.4
6.12
3-10
6
Oral GTT (2 h value)
151
198
178
13.47
<140
7
Lipid profile (TG in mg/dl)
170
220
193
14.27
<150
8
Ovarian volume (cc)
12
21
18
3.7
3-10
9
Antral Follicle Count
30
56
42
10.17
5-10 (in each ovary)

By using monkey as an experimental model, it has been found that alternation of DNA methylation patterns might lead non-human primates predispose to polycystic ovary syndrome (PCOS). In addition, in granulosa cells that derived from patients, 12245 differential methylated CpG sites were detected in the PCOS groups, which suggested that loci specific and/or global DNA methylation alteration may play a direct role in the initiation and development process of PCOS. Since DNA methyl-transferase (DNMTs) are the major enzymes for the depositing and protection of DNA methylation and some other histone modifiers also play a role for the maintenance of DNA methylation at specific loci aberrant express of these enzymes may also trigger the occurrence of PCOS in humans. Therefore, study the expression levels and catalytic activity of these enzymes may create a new direction for the investigation of PCOS and shed light on the further treatment of this disorder.

Conclusion

A subset of obese PCOS with very high AMH levels who otherwise appear to be severe hyper-responders may require the addition of LH to higher doses of FSH for inducing ovulation, possibly because of presence of FSH receptor resistance or polymorphism.

References

1. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, et al. (2004) Anti-Mullerian hormone expression pattern in the human ovary: Potential implications for initial and cyclic follicle recruitment. Molecular Human Reproduction 10: 77-83.

2. Tajima K, Orisaka M, Mori T, Kotsuji F (2007) Ovarian theca cells in follicular function. Reprod Biomed Online 15: 591-609.

3. Alviggi C, Humaidan P (2013) A common polymorphic allele of the LH betasubunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology. Reprod Biol Endocrinol 11: 51.

4. Xu N, Kwon S, Abbott DH, Geller DH, Dumesic DA, et al. (2011) Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)- like phenotypes in prenatally androgenized rhesus monkeys. PLoS One 6:e27286.

5. Xu J, Bao X, Peng Z, Wang L, Du L, et al. (2016) Comprehensive analysis of genome-wide DNA methylation across human polycystic ovary syndrome ovary granulosa cell. Oncotarget 7: 27899-27909.

 6. Okano M, Bell DW, Haber DA, Li E (1999) DNAmethyl-transferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247-57.

7. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16: 6-21.

8. Zhang T, Termanis A, Özkan B, Bao XX, Culley J, et al. (2016) G9a/GLP complex maintains imprinted DNA methylation in embryonic stem cells. Cell Rep 15:77-85.

 

Comparison of efficacy and tolerability of freeze-dried and liquid formulations of urinary human chorionic gonadotropin for triggering ovulation

Tejshree Singh, MBBS, CPSDGO, MD, DNB*, Abha Majumdar, MBBS, MS, FICS**

*Consultant Infertility Unit, Department of Obstetrics and Gynaecology, Kolmet Hospital & Research Centre, New Delhi, India

**Senior Consultant and Head of the Unit of IVF and Human Reproduction, Department of Obstetrics and Gynaecology

Objective

Subjects and Methods Results To compare the efficacy and tolerability of freeze-dried and liquid formulations of urinary human chorionic gonadotropin (hCG) for inducing final oocyte maturation and triggering ovulation.

Subjects and Methods

In a randomized, single-centre study, infertile women (n=100) received single injections of urinary hCG (5000 IU) from reconstituted freeze-dried (1.0 mL of 5000 IU /mL) and liquid (0.5 mL of 5000 IU /0.5 mL) formulations in random order, when their ultrasounds showed one or more dominant follicles of size 18mm or above. Blood samples were taken after 36h for determination of hCG concentration by immunoassay using direct chemilluminometric technology. Follicular rupture was assessed by means of another ultrasound undertaken 48h following the injection of hCG and serum progesterone levels undertaken 8 days later

The mean serum hCG levels achieved 36 hours post hCG injection were 74.05 mIU/ml for the freeze-dried formulation and 69.65 mIU/ml for the liquid formulation. The mean difference between these levels was 4.400 (95%confidence interval -19.002 to 10.202) which is statistically not significant (p-value 0.545). These levels were equally effective for triggering ovulation. The mean serum progesterone levels achieved day 8 post hCG, were 8.452 ng/ml for the freeze-dried formulation and 8.228 ng/ml for the liquid formulation. Both formulations were tolerated well; the liquid formulation of hCG was associated with fewer adverse effects.

Discussion

The levels of hCG required to trigger follicular rupture are anywhere between 20 to 45 mIU/ml. As ovulation will happen about 36-48 hours after the injection of hCG, procedures can be scheduled to take advantage of this time sequence.

Review of literature

The liquid formulation of recombinant hCG was shown to be bioequivalent to the freeze-dried formulation, with the same efficacy and no clinically significant differences in tolerability.

Conclusion

Our study shows that the liquid formulation of urinary hCG provides the same efficacy as the freeze-dried formulation when used to trigger final follicular rupture, is convenient to use and has better tolerability.

Preimplantation Genetic Screening For All 24 Chromosomes By Microarray Comparative

Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

ABSTRACT

CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis

INTRODUCTION

The last decade has seen a focused and persistent effort toward developing means and technologies to identify embryos that are most likely to implant and grow till term resulting in the birth of a healthy live baby. At present, morphology evaluation is the mainstay of embryo selection since it is noninvasive and easy to perform. However, it has not proved to be a very efficient method for selecting embryos since implantation rates and clinical pregnancy rates (PR) per transferred embryo continue to be very low. Among many factors, one major reason for poor reproductive potential of embryos generated in vitro is the prevalence of aneuploidies in such embryos. The rate of aneuploidy rises with increasing maternal age] but it is only moderately associated with morphology. Therefore, a significant percentage of even the “most ideal” embryos selected for transfer will be aneuploid, resulting in poor reproductive outcome. Moreover, transferring aneuploid embryos can be potentially dangerous since aneuploidy is the most common cause of miscarriage and the most common genetic abnormality in embryos. Preimplantation genetic screening (PGS), even though highly invasive in nature, started out as a very promising concept allowing embryos to be screened for aneuploidies before being selected for transfer. However, this older version of PGS failed to live up to expectations, as numerous authors failed to show improvement in in vitro fertilization (IVF) outcomes with PGS using fluorescence in situ hybridization (FISH), in which chromosomal analysis of not all but only a few chromosomes was performed. With the advent of new validated platforms for comprehensive chromosomal screening (CCS) such as single nucleotide polymorphism array, microarray comparative genomic hybridization (array CGH), and quantitative polymerase chain reaction (PCR), capable of analyzing all 24 chromosomes, now an improved version of PGS involving 24 chromosome copy number analysis is being expected to be a likely remedy for the earlier shortcomings. This retrospective case–control study seeks to examine the efficacy of PGS applied to poor prognosis patients, given the relative paucity of information concerning the use of modern 24 chromosome copy number analysis for this patient group. The objectives of this study were to establish the incidence of aneuploidy in such patients undergoing IVF with poor prognosis and to undertake a retrospective comparative analysis of the clinical outcomes of these patients undergoing IVF PGS cycles with non PGS, IVF controls.

Prevalence of metabolic syndrome in relation to body mass index and polycystic ovarian syndrome in Indian women

ABSTRACT
OBJECTIVE: To study the prevalence of metabolic syndrome (MBS) in Indian women and to see how does it correlate to body mass index (BMI) and polycystic ovarian syndrome (PCOS) in this population. STUDY DESIGN: Prospective cross sectional observational study. SETTING: Infertility clinic of a tertiary center. MATERIALS AND METHODS: Two hundred women, 120 with PCOs and 80 age-matched controls were enrolled. The prevalence of MBS was studied in the women with and without and was co related to BMI by further subgrouping as team (BMI 23 kg/m2). The sample size was: team controls-40, obese controls-40, team PCOS80. Each subject underwent a physical examination and laboratory evaluation for the diagnosis of MBS, which was defined according to the guidelines of National Cholesterol Education Program Adult Treatment Pamel (NCEP ATP III) 2005. INTERVENTION: None. MAIN OUTCOME MEASURES: Main Outcome Measures: Subjects with and without PCOs were compared with each other for the prevalence of MBS, and similarly team subjects were compared with obese subjects. Receiver operator characteristic (ROC) curves were obtained for both the PCOS and non PCOS population separately, co-relating the prevalence of MBS with BMI. These ROC curves were used to establish the cut off values of BMI, which could best predict the risk of MBS. RESULTS: The prevalence of MBS was significantly higher in the women with PCOS, as compared to age matched controls. Similarly, when BMI was considered, MBS was more prevalent in overweight subjects than in lean subjects with or without PCOS. In subgroup analysis, the presence of PCOS had a lesser impact on the prevalence of MBS as compared to non PCOS controls with higher BMI. The relative risk of MBS increased as follows: lean controls 1, lean PCOS 2.66, obese controls 5.33, and obese PCOS 6.5. The most appropriate cut off level of BMI for predicting the risk of MBS in Indian women without PCOS seems to be 23 kg/m2 , whereas, with PCOS, it was 22.5 kg/m2 . CONCLUSION: MBS is more prevalent in women with PCOS. However, obesity is an independent and stronger risk factor for developing MBS. To reduce the risk of MBS and its related long term health consequences, lifestyle modification is advisable above BMI of 23 kg/m2 in the normal population and 22.5 kg/m2 in women with PCOS.

INTRODUCTION

Polycystic ovarian syndrome (PCOS) is common disorder, affecting approximately 5–10% of the women in reproductive age group.[1,2] It is characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. The other metabolic abnormalities associated with PCOS are obesity, dyslipidemia, insulin resistance, glucose intolerance, and hypertension, which confer an increased risk of long term health consequences such as type II diabetes mellitus and cardiovascular risk.[3] Most of these metabolic features are also shared by the syndrome X or metabolic syndrome (MBS), which is associated with atherosclerosis, hypertension, dyslipidemia, coronary artery disease, and diabetes. Some of the factors affecting the prevalence of MBS are age,[4,5] obesity,[4] insulin resistance,[6] and underlying PCOS.[7] Till date, there are few studies, mainly from the American population[8 10] and still fewer from the European continent,[11,12] which have addressed the prevalence of MBS in women with PCOS. There is a scarcity of data from Asian population.[13,14] Moreover, in most of these studies, the women with PCOS were found to have a higher body mass index (BMI) and waist circumference, as compared to the controls, which could have confounded in the higher prevalence of MBS. This study was undertaken with an aim of comparing the prevalence and different characteristics of MBS in Indian women with PCOS and age matched controls. To negate the confounding effect of the high BMI associated with PCOS, subgroups of lean and obese women were studied separately for the prevalence of MBS. In order to reduce the serious long term consequences related to MBS, we have attempted to find out the predictors of MBS, and the action points, at which screening for MBS and lifestyle modification would be beneficial, in respect to preventing, or modifying long term morbidity.

in vitro fertilization for all or few only?

Over the last three and a half decades after the first successful in vitro fertilization (IVF), the technology has been rolling forward in all directions; so that a technique which was once considered the last resort to successful fertility has almost become the first choice. Why is it so? Is IVF flawless, without complications, and has the highest probability of fulfilling ones wish to correct the underlying disorder causing sub-fertility and promote natural conception appear redundant today! One would argue that it is not so; IVF has a flip side-complications, side effects, failures, and financial and emotional exhaustion are all part of it. But then, on the other hand, this technique is truly the only way to parenthood for a lot of medical conditions that cannot be rectified by developments within the scope of drugs and surgery. It is for this sector of patients who crave for a child, who are willing to forfeit the increased risk of congenital abnormality as well as maternal complications imposed by the technology in order to fulfill their dream of parenthood.

Originally, IVF was the only way out for women with blocked or irreparably damaged fallopian tubes. With the advent of intracytoplasmic sperm injection (ICSI), the indications of IVF expanded; initially to severe male factor infertility and then to couples with unexplained infertility. With the development of oocyte and embryo donation as well as surrogacy, the use of IVF could be extended to a lot more couples who would otherwise not have a chance to parent their own child. All these techniques involving use of third party for lending their gametes, embryos, or uteruses have made it possible for women with ovarian failure or premature menopause, couples with no gametes, and for women with absence of a functional uterus respectively to be able to carry a child. Becoming a gestational or true genetic mother has turned into reality for so many desperate mothers. Lately, the technology of oocyte and ovarian tissue freezing for fertility preservation before going through chemotherapy has become another turning point in the life cycle of IVF which now enables women to be able to parent their own child at a later date. Recently, the development of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) by testing one cell from “in vitro embryos” has further increased the possibility for couples to have disease free healthy babies.

However, after having said all this about the use and applications of this rapidly advancing technology, we also must understand that human reproduction is a very inefficient process and IVF mirrors this “wastage” at every stage. One in five cycles undertaken to entangle many more desperate couples into IVF who have become old wanting a child and will refuse to see any health risks associated with pregnancies at this age.

The IVF industry is powered by photographs of beautiful babies held by proud parents. Being childless is so traumatic for manythat almost any cost seems worth paying. Indeed, the birth of a desperately wanted child is a priceless miracle for a couple who has otherwise given up all hope. The technology must continue to grow as it is one of the greatest advancement in the field of medicine where “life is created outside the human body”. All we need is good and strong legislation to safeguard mothers as well yields no eggs at all, all retrieved oocytes do not fertilize, and 90% of embryos replaced do not survive. Of those that do, a few result into life-threatening ectopic pregnancies requiring urgent abortion while others miscarry. The number of peri-natal deaths is also double the rate of spontaneous conceptions partly because multiple pregnancies are more common with IVF and often result in premature delivery.

More than a failure is the iatrogenic complications of this technology. Amongst the foremost complications of IVF is the dreaded ovarian hyper-stimulation syndrome (OHSS) which is the direct effect of drugs used for ovarian stimulation and may become a real life threatening hazard. One woman in 12/cycle has mild symptoms, but two in every 100 are so ill that they need hospital admission and intensive care on account of the complications of OHSS. However, the biggest price to be paid cannot just be measured in terms of money or health risks. It is the emotional roller-coaster which goes with drugs used for treatment, egg retrieval, semen collection, embryo replacement, freezing of surplus embryos, and above all, high hopes and crushing disappointment.

At this stage with so many advances happening globally came the role of the middle man who tried to bring a third party to the intending parents. Policy makers, who could foresee and perceive the antecedent exploitation of such developments, restricted the use of third party reproduction in their jurisdiction and countries. However, a lot of developing countries gave into these newly developed technological advancements, partly because of lack of a regulatory governing body and mostly because of monetary gains. ICSI started being used for all women undergoing IVF, oocyte donation to compensate for sub optimal standards of IVF clinics, embryo donation for anyone and everyone especially for women of over 50 years of age, surrogacy for social reasons as well as for single fathers and gay couples, oocyte freezing for women wanting to delay pregnancy for personal and professional reasons, and PGD and PGS for sex selection of the unborn baby.

Out of the so many enumerated “misuses” of the technology, there are instances where law has been trying to control the health of women by limiting the age of surrogates to 35 and the age of oocyte donor also to below 35 to maximize the genetic normalcy of the unborn child. Nevertheless, there is no law to limit the age

of a woman wanting to carry a child for her own self by donated oocyte or donated embryo. This presents yet another risk in that even if we were to set aside the exaggerated maternal mortality and morbidity with these older age pregnancies, we also seem to be unfairly deciding the fate of the unborn child by allowing them to be parented by couples who are aged like grandparents and are no longer capable of providing the same care a younger couple is able to provide, the way nature intended it. Who has given us the right to choose the destiny of these children? Or is this another “feather in our cap” which we very proudly advertise as the unborn child who might get entangled in this rut of human race unknowing and unaware of the complications.


Sir Ganga Ram Hospital

Rajendra Nagar

New Delhi, India-110060.

For appointments: +91-11-42254000, 42251800.

For tracking progress of IVF: +91-11-42251777 (9AM – 5 PM, +91-8375990881 (Emergency call only 5PM-9AM),

Email: [email protected]

Genesis Clinic

F-431

New Rajendra Nagar,

Landmark: Shankar Road Main Market, New Delhi -110060
Phone-: 011-28742454 , 28745692 , 28741270 , 45011438
Mob.: +91-8375990881(Emergency call only)

Email: [email protected]

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