Journal of Human Reproductive Science
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 3  |  Issue : 2  |  Page : 91-94
 

Demographic characteristics and clinical profile of poor responders in IVF / ICSI: A comparative study


Institute of Reproductive Medicine, Madras Medical Mission, Chennai - 600 037, India

Date of Submission04-May-2010
Date of Decision09-Jul-2010
Date of Acceptance28-Jul-2010
Date of Web Publication14-Sep-2010

Correspondence Address:
Nabaneeta Padhy
Institute of Reproductive Medicine, Madras Medical Mission, Chennai - 600 037
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-1208.69343

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   Abstract 

Background: Ovarian response varies considerably among individuals and depends on various factors. Poor response in IVF yields lesser oocytes and is associated with poorer pregnancy perspective. Cycle cancellation due to poor response is frustrating for both clinician and the patient. Studies have shown that women conceiving after poor ovarian response have more pregnancy complications like PIH and preeclampsia than women with normal ovarian response. In addition, poor ovarian response could be a predictor of early menopause. This paper studies various demographic and clinical profiles of poor responders and tries to look at the known and unknown factors which could contribute to poor ovarian response in IVF. Materials and Methods: Data were collected retrospectively from 104 poor responders who had less than four oocytes at retrieval and compared with 324 good responders for factors like age, BMI, type of sub fertility, duration of sub fertility, environmental factors like stress at work, smoking, pelvic surgery, chronic medical disorder, indication of IVF, basal FSH, mean age of menopause in their mothers etc. Results: Among the poor responders, 60.57% were above 35 years of age compared to 36.41% in control group, which is statistically significant. Mean age of menopause in mother was found to be four years earlier in poor responder group. Male factor and unexplained infertility were significantly (P<0.05) higher in good responders (P<0.05). Significant proportion (31.73%) of women in study group had undergone some pelvic surgery (P<0.05). Conclusion: Apart from age, prior pelvic surgery also could be used as predictors for poor ovarian response. Heredity also plays a major role in determining ovarian response.


Keywords: Gonadotrophin, ovarian response, pelvic surgery, poor responder


How to cite this article:
Padhy N, Gupta S, Mahla A, Latha M, Varma T. Demographic characteristics and clinical profile of poor responders in IVF / ICSI: A comparative study. J Hum Reprod Sci 2010;3:91-4

How to cite this URL:
Padhy N, Gupta S, Mahla A, Latha M, Varma T. Demographic characteristics and clinical profile of poor responders in IVF / ICSI: A comparative study. J Hum Reprod Sci [serial online] 2010 [cited 2019 Aug 17];3:91-4. Available from: http://www.jhrsonline.org/text.asp?2010/3/2/91/69343



   Introduction Top


Ovarian response can be defined as the reaction of the ovaries to exogenous stimulus. It varies considerably among individuals and in the same individual as well. [1] Ovulation induction and controlled ovarian stimulation aim at achieving a distinct ovarian response, which predicts the success of such treatment. [2] To select best embryos, it is important to obtain several embryos [3],[4] Poor response in IVF yields lesser oocytes and is associated with poorer pregnancy perspective. Older patients and patients with elevated basal FSH are known to respond poorly owing to the poor ovarian reserve. [5] Younger patients with no obvious cause are also found to respond poorly in IVF. In fact, poor responders can be those with low ovarian reserve and those with normal ovarian reserve but inherent low response to gonadotrophin. [1] Although no definite cause could be attributed, differences in metabolism of exogenous FSH could be responsible for the varying ovarian response. [6] Hence, age cannot be taken as a sole predictor of cumulative pregnancy to identify poor prognosis cases. [7] There is a need for predictors of poor response which could be used to reduce cycle cancellation rate. Antral follicle count may be considered as the best single predictor for poor ovarian response than age and endocrine markers. [8] Apart from basal FSH and AFC, several other factors like basal inhibin and AMH are currently being investigated as predictors of ovarian response. There are various female and male lifestyle habits, which could possibly affect success rates in ART. Smoking has been proved to affect IVF outcome negatively whereas role of stress, caffeine and alcohol is inconclusive [9]

Cycle cancellation due to poor response is frustrating for both clinician and the patient and demands meticulous follow up. Studies have shown that women conceiving after poor ovarian response have more pregnancy complications like PIH and preeclampsia than women with normal ovarian response. [10] In addition, poor ovarian response could be a predictor of early menopause. [11] This paper studies various demographic and clinical profiles of poor responders and tries to look at the known and unknown factors, which could contribute to poor ovarian response in IVF.


   Materials and Methods Top


Patients undergoing IVF/ICSI from Jan 2008 to Jan 2009 were included in the study. Patients having lesser than four oocytes at retrieval and those cycles which were cancelled due to poor follicular development, were defined as poor responders. [12] 104 poor responders according to the above criteria were included in the study and were compared with 324 good responders. These patients had been allocated to different protocols depending on the basal FSH, AFC and age (Antagonist / GnRHa long protocol). The protocol for pituitary down regulation, ovulation induction, and HCG administration was consistent throughout for both the study and the control group.

Data were collected retrospectively from the records of all 104 poor responders and compared with those of the good responders. We looked at various demographic characteristics like age, BMI, type of subfertility, duration of subfertility, environmental factors like stress at work and smoking in any of the partners. Both groups were also compared for clinical profile like pelvic surgery, chronic medical disorder, and indication of IVF, basal FSH, and mean age of menopause in their mother.

Study design

Retrospective comparative study.

Statistical analysis

GraphPad QuickCalc was used for the data computation. Chi-square test and Fisher exact test were used for comparing categorical data. P value of less than 0.05 was taken to be significant.

Unpaired t test was used to compare continuous data.


   Results Top


Among the poor responders, 60.57% were above 35 years of age compared to 36.41% in control group, which is statistically significant. Incidence of primary subfertility in the two groups was similar [Table 1]. More than half of women in poor responders group were in stressful jobs as compared to the control group. Most of the women came from the urban set up in both groups but significantly higher in study group (P=0.01). Smoking in either of partner could not be specifically correlated to any of the groups (P=0.10).
Table 1: Demographic characteristics

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Mean age of menopause in mother was found to be four years earlier in poor responder group, which is statistically significant [Table 1]. Poor responders were found to have prolonged subfertility compared to the control group (P<0.05).

Causes of infertility

Major indication of IVF in poor responder group was multifactor [Table 2] and hence the other causes as sole factor were less found among them. Male factor and unexplained infertility were significantly (P<0.05) higher in good responders (P<0.05). In contrast, unexplained and PCOS were rare among poor responders. Incidence of endometriosis was similar in both groups; 25.96% women in poor responder group had high basal FSH (>10iu) which is statistically extremely significant. Majority of women in both groups had regular periods and had good endometrial development [Table 3].
Table 2: Causes of infertility

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Table 3: Clinical profile


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Medical or surgical illness

Significant proportion (31.73%) of women in study group had undergone some pelvic surgery (P=0.01). Prevalence of diabetes and hypertension were similar between two groups. Among different types of surgeries, excision of endometriotic cyst was the major surgery in poor responder as opposed to ovarian drilling for PCOS in good responders [Table 4].
Table 4: Medical or surgical illness

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   Discussion Top


Stress and infertility are closely associated. Stress in life may predispose to infertility, whereas stress of infertility affects quality of life in both partners equally. [13] Working women are exposed to stress of travelling, environmental pollution and passive smoking in addition to stress at work. Various negative life events preceding IVF can affect adversely the outcome including number of oocytes harvested during retrieval. [14] Environmental pollution can affect the sperm parameters adversely thereby leading to infertility. [15] As evident from our study, poor responders group has majority of working women and most of them come from an urban set up. Effect of smoking is inconclusive from our study as most of the women who were included in this category had passive smoking only as smoking among middle class Indian women is rare. Prolonged sub fertility among poor responders specifies that in addition to age, there is some other unknown but significant factor, which plays a role. This decreased response could be attributed to a hereditary factor as the mean age of menopause in their mothers is significantly lower than those in the good responders. Studies have shown that expression of follicle stimulating hormone receptor (FSHR) in granulosa cells varies among poor, moderate and high responders. Low expression of FSHR at the mRNA level in poor responders plays a critical role and can be correlated to the role of heredity as seen in our study. [16],[17],[18]

Factors causing subfertility perhaps do not affect outcome of ovarian response except endometriosis. In fact, endometriosis is a major cause of poor response in IVF in younger patients. But in our study both the groups have comparable number of patients with endometriosis. This may be due to the fact that most of the poor responders have multiple factors causing infertility, which includes endometriosis as well. In contrast, patients with unexplained subfertility do not present with poor response usually [Table 3] as the defect in these patient may be ovulatory, peritoneal, fertilization or implantation related. Although significant number of patients in study group had higher basal FSH, their endometrial development is comparable with their counter parts, indicating that they represent a group of normally ovulating women. [19],[20]

Effect of chronic medical disorders like diabetes and hypertension is very little on the ovarian response as seen in our study. Prior pelvic surgery poses a major risk factor for poor ovarian response as there is a significant correlation of pelvic surgery and poor ovarian response (P=0.01) in our study. This may be due to insult to the ovarian vascularity during such surgeries. Vascularity could be compromised by direct injury during surgery or due to post-operative infection leading to micro thromboembolism.

The major drawback of this study is probably the different protocols used for different groups of patients. Till now, there is no clear consensus about an ideal stimulation regimen for poor responders, as retrospective analysis of various protocols used for them did not reveal any differences. [21] Some studies have indicated superiorly of antagonist protocol in terms of reduced duration of ovarian stimulation, less use of GTH, fewer cycle cancellation and more oocyte yield, [22] whereas others have shown the advantages of using short agonist protocol. In our practice, we have observed fewer cycle cancellation with antagonist protocol and hence used antagonist protocol for the patients who were having low AFC and high FSH and were expected to have poor response. Studies have proved that increasing the dose of gonadotrophin does not rectify poor response; hence, amount of gonadotrophin used has not been taken into account in our study. [5],[23]


   Conclusion Top


Poor responders are a challenge to the IVF specialists and need to be investigated for the cause. Age is an established indicator of poor response as with advancing age there is depletion of primary oocytes. Apart from age, endometriosis and prior pelvic surgery also could be used as predictors for poor ovarian response. Above all, heredity also plays a major role and needs to be investigated further.

 
   References Top

1.Lashen H, Ledger W. Management of poor responders in IVF. Hum Reprod 1999;14:964-9.  Back to cited text no. 1      
2.Fauser BC, Diedrich K, Devroey P, Evian Annual Reproduction (EVAR) Workshop Group 2007. Predictors of ovarian response: Progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update 2008;14:1-14.  Back to cited text no. 2      
3.Wood C, McMaster R, Rennie G, Trounson A, Leeton J. Factors influencing pregnancy rates following in vitro fertilization and embryo transfer. Fertil Steril 1985;43:245-50.  Back to cited text no. 3      
4.Templeton A, Morris JK, Parslow W. Factors that affect outcome of vitro fertilisation treatment. Science 1996;348:1402-6.  Back to cited text no. 4      
5.Klinkert ER, Broekmans FJ, Looman CW, Habbema JD, Te Velde ER. Expected poor responders on the basis of an antral follicle count do not benefit from a higher starting dose of gonadotrophins in IVF treatment: A randomized controlled trial. Hum Reprod 2005;20:611-5.  Back to cited text no. 5      
6.Ben Rafael Z, Strauss JF, Mastroianni L, Flickinger GL. Difference in ovarian stimulation in human menopausal gonadotrophin treated women may be related to follicle stimulation hormone accumulation Fertil Steril 1986;46:586-92.  Back to cited text no. 6      
7.Hendriks DJ, te Velde ER, Looman CW, Bancsi LF, Broekmans FJ. Expected poor ovarian response in predicting cumulative pregnancy rates: A powerful tool. Reprod Biomed Online 2008;17:727-36.  Back to cited text no. 7      
8.Lαszlσ FJ, Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD, et al. Predictors of poor ovarian response in vitro fertilization: A prospective study comparing basal markers of ovarian reserve. Fertil Steril 2002;77:328-36.  Back to cited text no. 8      
9.Klonoff-Cohen H. Female and male lifestyle habits and IVF: What is known and unknown. Human Reproduction Update Advance Access published on February 11, 2005. Hum Reprod Update 2005;11:179-203.  Back to cited text no. 9      
10.Van Disseldorp J, Eijkemans R, Fauser B, Broekmans F. Hypertensive pregnancy complications in poor and normal responders after in vitro fertilization. Fertil Steril 2010;93:652-7.  Back to cited text no. 10      
11.Farhi J, Homburg R, Orvieto R, Ben Rafael Z. Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: A clinical sign of impending onset of ovarian failure pre-empting the rise in basal follicle stimulating hormone levels. Hum Reprod 1998;13:241-3.  Back to cited text no. 11      
12.Lawson R, El-Toukhy T, Kassab A, Taylor A, Braude P, Parsons J, et al. Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: A life table analysis. Hum Reprod 2003;18:527-33.  Back to cited text no. 12      
13.Chachamovich J, Chachamovich E, Fleck MP, Cordova FP, Knauth D, Passos E. Congruence of quality of life among infertile men and women: Findings from a couple-based study. Hum Reprod 2009;24:2151-7.  Back to cited text no. 13      
14.Ebbesen SM, Zachariae R, Mehlsen MY, Thomsen D, Hψjgaard A, Ottosen L, et al. Stressful life events are associated with a poor in-vitro fertilization (IVF) outcome: A prospective study. Hum Reprod 2009;24:2173-82.  Back to cited text no. 14      
15.Hammoud AO, Sanderson M, Gibson M, Carrell DT, Jones K, Peterson CM. Air pollution is associated with reduced sperm motility in exposed men. Fertil Steril 2008;90:S187-8.  Back to cited text no. 15      
16.Cai J, Lou HY, Dong MY, Lu XE, Zhu YM, Gao HJ, et al. Poor ovarian response to gonadotrophin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells. Fertil Steril 2007;87:1350-6.  Back to cited text no. 16      
17.Chen SH, Escudero T, Cekleniak NA, Sable DB, Garrisi MG. Santiago Munne Maternal balanced translocation is a risk factor for poor response to ovarian stimulation. Fertil Steril 2002;78:S21.  Back to cited text no. 17      
18.Achrekar SK, Modi DN, Desai SK, Mangoli VS, Mangoli RV, Mahale SD.Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women. Fertil Steril 2009;91:432-9.  Back to cited text no. 18      
19.Ferraretti AP, Gianaroli L, Magli MC, Bafaro G, Colacurci N. Female poor responders. Mol Cell Endocrinol 2000;161:59-66.  Back to cited text no. 19      
20.Silverberg KM, Ormand RA, Hansard LJ, Vaughn TC. Poor response to ovarian hyperstimulation predicts spontaneous ovulation. Fertil Steril 2001;76:S96-7.  Back to cited text no. 20      
21.Vollenhoven B, Osianlis T, Catt J. Is there an ideal stimulation regimen for IVF for poor responders and does it change with age. J Assist Reprod Genet 2008;25:523-9.  Back to cited text no. 21      
22.Marci R, Caserta D, Dolo V, Tatone C, Pavan A, Moscarini M. GnRH antagonist in IVF poor-responder patients: Results of a randomized trial. Reproduc BioMed Online 2005;11:189-93.  Back to cited text no. 22      
23.Khalaf Y, El-Toukhy T, Taylor A, Braude P. Increasing the gonadotrophin dose in the course of an in vitro fertilization cycle does not rectify an initial poor response. Euro J Obstet Gynecol Reprod Biol 2002;103:146-9.  Back to cited text no. 23      



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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