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ET Cycles and Sickle Cell Trait
Brief Report
SUCCESSFUL OUTCOME AFTER INTRACYTOPLASMIC SPERM INJECTION AND EMBRYO TRANSFER (ICSI AND ET) WITH INTRAVENOUS IMMUNOGLOBULIN (IVIG) TREATMENT IN A COUPLE WITH PREVIOUS REPEATED FAILED ICSI / ET CYCLES AND SICKLE CELL TRAIT Sohani Verma, Alok Teotia and Astha Mishra From the Department of IVF, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110044, India. Correspondence to: Dr. Sohani Verma, Sr. Consultant, Department of Obstetrics and Gynaecology and Incharge IVF Lab, Department of IVF, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110044, India. Infertile couples with repeated in vitro fertilization (IVF) failures pose a difficult problem. Unsuccessful implantation following transfer of good quality embroyes is usually contributed to the poor receptivityof the endometrium involving both hormonal and immunological factors. Although exact role is still disputed, elements of the immune system are probably involved in at least some of the cases. Intravenous immunoglobulin (IVIG) is well known to have strong immunomodulating effects in several well -established disorders, and has been tried in unexplained reproductive failures. It is also imperative to screen the infertile couples thoroughly to minimize the risk of transmitting any abnormality to the offspring. In the case presented, IVIG was administered following ICSI and ET. Sickle cell trait in both partners was detected only after the ET. Successful implantation was achieved and chorionic villus sampling to exclude sickle cell disease was performed during the first trimester of pregnancy. A healthy female child with a birth weight of 3000 grams was born by caesarian section at full term. However, large well-structured studies examining the benefits of immunological evaluation and treatment are necessary before definite recommendation for the routine use of IVIG in repeated unexplained IVF failure can be made. Key words: Repeated failed ICSI/ET cycles, Intravenous immunoglobulin (IVIG), sickle cell trait.
RECENT advances in assisted reproduction techniques (ART) have revolutionized the treatment of infertile couples. However, despite continued research, “take home baby rates” still remain low, with unexplained repeated implantation failure of good quality in vitro generated embryos. Several therapeutic approaches have been suggested to improve the success rates. A thorough pre-treatment screening and counselling is essential to optimize the couple’s chances of having a healthy child. One such case, emphasizing the importance of above issues is presented here.
stimulation and intrauterine insemination (IUI), followed by three attempts of invitro fertilization using micromanipulation technique - ICSI. At each IVF attempt, good quality embryos (once blastocyst and twice 8 cell embryos) were transferred with negative outcome. She had a documented history of severe ovarian hyper stimulation syndrome (OHSS) - grade IV (Golon’s classification) [1] during her first IVF treatment cycle in USA immediately after the oocyte retrieval, requiring intensive inpatient monitoring and management.
CASE REPORT
The couple requested to try one further attempt of ICSI and ET. They were counselled in depth especially in view of the previous history of severe OHSS and three earlier unexplained implantation failures despite good quality embryos.
A 27-year-old female with a 5-year history of primary infertility and her 36-year-old husband - an NRI couple settled in USA (originally from Orissa) presented at the out patient department of Indraprastha Apollo Hospitals, New Delhi in September 2003. The couple had already undergone extensive infertility investigations and treatment in USA where the cause of infertility was attributed to polycystic ovarian syndrome (PCOS) in female and severe oligo-astheno-teratozoospermia (severely reduced sperm count and motility, and increased number of abnormal forms) in the male partner. All other tests including immune profile of the female and karyotyping of both partners were normal. However, the couple were never screened for haemoglobinopathies.
During the interview, possible theoretical reasons for the implantation failure were discussed and potential beneficial role of intra venous immunoglobulin (IVIG) was appraised. This was emphasized to the couple that neither the cause of implantation failure nor the efficacy of IVIG in its prevention is clearly established at present. They were counselled about the possible side effects of IVIG and given time to make an informed decision as to the trial of IVIG therapy in their ICSI / ET treatment cycle.
The couple had already undergone four cycles of ovarian
They were advised haemoglobin electrophoresis to rule 57
Apollo Medicine, Vol.1 September 2004
Brief Report
out thalassemia / sickle cell abnormality. As the couple had come to India on a short vacation, they requested to start the treatment immediately.
Chorionic villous sampling was performed at 11 weeks gestation, which reported the fetus to have sickle cell trait only. Antenatal period of the patient was uneventful. She delivered a healthy, female baby of 3 kg weight at term by elective LSCS due to high head and patient’s reluctance to try for the vaginal delivery.
Pituitary down regulation was achieved by subcutaneous Buserelin acetate 0.5 mg once daily (Suprefact; Aventis Pharma, Germany) commencing on Day 21 of the cycle using long protocol regime. Following this controlled ovarian hyper stimulation was initiated with recombinant FSH (Gonal-F; Sereno, Italy) 150 IU daily and follicular growth and endometrial development were monitored using transvaginal ultrasonography. On day 11 of the FSH therapy more than three leading follicles of 18-20 mm diameter with an endometrial thickness of 9 mm were observed on ultrasonography. Transvaginal colour Doppler studies demonstrated good perifollicular vessels, low resistance flow in bilateral uterine arteries (RI - Resistive Index 0.6) and the presence of endometrial vessels up to the inner layer (zone 3 as defined by Apple Baum) [2]. Injection HCG (Profasi; Serono, Italy) 10,000 IU was administered and 34 hours later 18 oocytes were retrieved by transvaginal ultrasound guided follicular aspiration. Prophylactic human albumin 20% (Zenalb 20 – Bio Products Laboratory, UK) 200 mL intravenously was given to the patient during the oocyte retrieval procedure in view of the number of follicles and her previous history of severe OHSS.
DISCUSSION Assisted reproductive techniques such as IVF, ICSI and ET are now widely available for the infertile couples. Despite significant improvement in the success rates, unexplained repeated (three or more attempts) implantation failure of good quality embryos remains a frustrating, unsolved mystery. Various research studies have indicated that endometrial receptivity involves both hormonal and immunological factors [3]. However, the roles that allo immunity and auto immunity may play in reproductive failure, have not been clearly established. Several immune tests (anti phospholipid antibodies, anti nuclear antibody, Lupus anticoagulant, natural killer cells, leucocyte antibodies) are available but controversy still exists on their precise role in such cases. Even when all conventional immune tests are negative as in this case, patients may face repeated reproductive failure. Intravenous immunoglobulins, first given to the recurrent aborters with anti-phospholipid syndrome, have been administered to the unexplained repeated aborters and IVF / ET failures with variable results and controversial opinions [3-5-8]. IVIG is purified, concentrated immunoglobulin G antibodies pooled from human blood donors. Due to its strong “immunomodulating” effect in several well established disorders, high - dose intravenous immunoglobulin (IVIG) has been proposed and used as an alternative for immunotherapy with allogenic leucocytes, in patients with unexplained recurrent spontaneous abortion [4]. IVIG reduces the activation of natural killer cells (NK cells) and NK killing activity both in vitro and in vivo. These NK cells are present within the decidua and play a crucial role in successful implantation [3]. Studies have been reported showing improved success rate in IVF cycles with the use of high dose IVIG [5,3,6] as found in this case, while other reports have shown no benefit [7,8]. Although IVIG is usually well tolerated by the patients, the occurrence of major and minor side effects is uncommon and infectious morbidity is low [9], however, in the absence of data from the large controlled trials, its use is still regarded as experimental and proper informed consent of the patient is essential.
All oocytes were subjected to micromanipulation technique - ICSI. Fertilization was achieved in 9 of these and 48 hours later four embryos (grade I × 2, grade II × 2) were transferred into the uterine cavity. Having obtained the couple’s written consent, intravenous immunoglobulin (Sandoglobulin; Novartis, UK) was given to the patient at a dosage of 400 mg / kg prior to the ET. Luteal support was initiated in the form of micronized vaginal progesterone (Susten; Sun Pharma, India) 400 mg twice daily. The couple were although advised and repeatedly reminded to have Hb Electrophoresis since their first visit but they produced the test report only on the day of ET. Both partners tested to be positive for the sickle cell trait. They were counselled in detail and made aware that a chorionic villous sampling (CVS) would be recommended if pregnancy is achieved. On day 10 - post embryo transfer, patient developed moderate OHSS requiring hospitalization. Her condition was monitored closely and managed conservatively using intravenous normal saline, albumin, low molecular weight (LMW) Heparin and ascitic fluid paracentesis twice. Her serum hCG measurements on day 14 and 16 confirmed successful implantation and an ultrasound 4 weeks post ET demonstrated a singleton live intrauterine pregnancy. Her OHSS settled completely by this time and she was discharged home. IVIG was repeated once more 4 weeks after the first administration at the same dosage. Apollo Medicine, Vol. 1, September 2004
Severe OHSS is a potentially life threatening complication not uncommonly seen in PCOS patients undergoing ovarian stimulation using Gonadotrophins, the reported incidence in literature varies between 6-60 % [10] . The exact mechanism responsible is unknown, the most widely accepted hypothesis 58
Brief Report
is that it originates from increased capillary permeability leading to extravasation of fluid - firstly into the ovary and than into the abdominal cavity [11]. OHSS is four times more likely to occur in conception cycles [12]. Albumin infusion at the time of oocyte retrieval has been suggested to be a successful prophylactic measure against the development of OHSS [13] but the efficacy has not been confirmed by more recent studies.
Obstet Gynecol Surv 1989; 44: 430-440. 2. Applebaum M. The uterine biophysical profile. Ultrasound Obstet Gynecol 1995 ; 5: 67-6 8. 3. Coulam CB, Goodman C. Increased pregnancy rates after IVF /ET with intravenous immunoglobulin treatment in women with elevated circulating C56 + cells. Early Pregnancy 2000 Apr; 4(2): 90-98. 4. Mueller-EcKhardt G. Immunotherapy with intravenous immunoglobulin for prevention of recurrent pregnancy loss : American Journal of Reproductive Immunology. 1994 Dec.; 32(4): 281-285.
In the case reported, there was a definite history of severe OHSS during the patient’s first IVF cycle immediately after oocyte retrieval. Prophylactic albumin infusion at the time of oocyte retrieval therefore was given which may have prevented the occurrence of OHSS initially however as soon as successful implantation started (day 10 post ET) patient did develop severe OHSS for which the patient was hospitalised and managed conservatively successfully.
5. Coulam CB, Krysa LW, Bustillo M. Intravenous immunoglobulin for in-vitro fertilization failure. Human Reproduction 1994 Dec; 9(12): 2265-2269. 6. Scher J, Salazar C. Clinical experience with IVIG Rx in patients with prior failed IVF pregnancies: report of 30 consecutive patients. Am J Reprod. Immunol. 2000 Aug; 44(2): 121-124.
Haemoglobinopathies are not uncommon in Indian origin population with a reported incidence of sickle cell disorder as 4.3% [14]. The clinical disease requires a double dose of the abnormal gene for expression of the clinical disease (homozygosity for the βs gene). Therefore, if both partners have sickle cell trait, the offspring will have 25% chance of having clinical sickle cell disease. The cardinal features of the disease include chronic haemolytic anaemia and recurrent painful episodes.
7. Balash J, Creus M, Fabregues F, Font J, Martorell J, Vanrell JA. Intravenous immunoglobulin preceding in vitro fertilization - embryo transfer for patients with repeated failure of embryo transfer. Fertil Steril 1996 March; 65(3): 655-658. 8. Stephenson MD, Fluker MR. Treatment of repeated unexplained in-vitro-fertilization failure with intravenous immunoglobulin: A randomised, placebo controlled Canadian trial. Fertil Steril 2000 Dec; 74(6): 1108-1113. 9. AL Clark. Clinical uses of intravenous immunoglobulin in pregnancy. Clinical Obstetrics & Gynecology 1999 June; 42(2): 368-380.
Although this patient had undergone several years of infertility treatment at various parts of the world, haemoglobinopathy screening was never done. When the couple were eventually advised the screening, they did not comply with the instructions until quite late. Were the couple diagnosed to have sickle cell trait earlier, they would have had the option of considering pre-implantation genetic diagnosis (PGD) in embryos using polymerase chain reaction (PCR) assay and that would have avoided the stress and anxiety they went through while waiting for the results of chorionic villous sampling. Fortunately, the report was favourable, hence they could continue the pregnancy and had the ultimate joy of having a healthy child.
10. Rizk B. Ovarian hyperstimulation syndrome. Progress in Obstetrics & Gynaecology 1994; 11; 311-349. 11. McManus Joanne, McClure Neil. Complications of assisted reproduction. The Obstetrician & Gynaecologist July 2002; 4(3); 124-128. 12. Haning RV, Strawn EY, Nolten WE. Pathophysiology of the ovarian hyper stimulation syndrome. Obstet Gynecol 1985 ; 66 : 22-24. 13. Asch RH, Ivery G, Goldsman M, Frederick JL, Stone SC, Balmaceda JP. The use of intravenous albumin in patients at high risk for severe ovarian hyper stimulation syndrome. Hum Reprod 1993; 8 :1015-1020.
REFERENCES
14. Balgir RS. Genetic epidemiology of the three predominant abnormal hemoglobins in India. J Assoc Physicians India 1996 Jan; 44(1) : 25-28.
1. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyper stimulation syndrome: an update review.
59
Apollo Medicine, Vol. 1, September 2004
SUCCESSFUL OUTCOME AFTER INTRACYTOPLASMIC SPERM INJECTION AND EMBRYO TRANSFER (ICSI AND ET) WITH INTRAVENOUS IMMUNOGLOBULIN (IVIG) TREATMENT IN A COUPLE WITH PREVIOUS REPEATED FAILED ICSI / ET CYCLES AND SICKLE CELL TRAIT Sohani Verma, Alok Teotia and Astha Mishra From the Department of IVF, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110044, India. Correspondence to: Dr. Sohani Verma, Sr. Consultant, Department of Obstetrics and Gynaecology and Incharge IVF Lab, Department of IVF, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110044, India. Infertile couples with repeated in vitro fertilization (IVF) failures pose a difficult problem. Unsuccessful implantation following transfer of good quality embroyes is usually contributed to the poor receptivityof the endometrium involving both hormonal and immunological factors. Although exact role is still disputed, elements of the immune system are probably involved in at least some of the cases. Intravenous immunoglobulin (IVIG) is well known to have strong immunomodulating effects in several well -established disorders, and has been tried in unexplained reproductive failures. It is also imperative to screen the infertile couples thoroughly to minimize the risk of transmitting any abnormality to the offspring. In the case presented, IVIG was administered following ICSI and ET. Sickle cell trait in both partners was detected only after the ET. Successful implantation was achieved and chorionic villus sampling to exclude sickle cell disease was performed during the first trimester of pregnancy. A healthy female child with a birth weight of 3000 grams was born by caesarian section at full term. However, large well-structured studies examining the benefits of immunological evaluation and treatment are necessary before definite recommendation for the routine use of IVIG in repeated unexplained IVF failure can be made. Key words: Repeated failed ICSI/ET cycles, Intravenous immunoglobulin (IVIG), sickle cell trait.
RECENT advances in assisted reproduction techniques (ART) have revolutionized the treatment of infertile couples. However, despite continued research, “take home baby rates” still remain low, with unexplained repeated implantation failure of good quality in vitro generated embryos. Several therapeutic approaches have been suggested to improve the success rates. A thorough pre-treatment screening and counselling is essential to optimize the couple’s chances of having a healthy child. One such case, emphasizing the importance of above issues is presented here.
stimulation and intrauterine insemination (IUI), followed by three attempts of invitro fertilization using micromanipulation technique - ICSI. At each IVF attempt, good quality embryos (once blastocyst and twice 8 cell embryos) were transferred with negative outcome. She had a documented history of severe ovarian hyper stimulation syndrome (OHSS) - grade IV (Golon’s classification) [1] during her first IVF treatment cycle in USA immediately after the oocyte retrieval, requiring intensive inpatient monitoring and management.
CASE REPORT
The couple requested to try one further attempt of ICSI and ET. They were counselled in depth especially in view of the previous history of severe OHSS and three earlier unexplained implantation failures despite good quality embryos.
A 27-year-old female with a 5-year history of primary infertility and her 36-year-old husband - an NRI couple settled in USA (originally from Orissa) presented at the out patient department of Indraprastha Apollo Hospitals, New Delhi in September 2003. The couple had already undergone extensive infertility investigations and treatment in USA where the cause of infertility was attributed to polycystic ovarian syndrome (PCOS) in female and severe oligo-astheno-teratozoospermia (severely reduced sperm count and motility, and increased number of abnormal forms) in the male partner. All other tests including immune profile of the female and karyotyping of both partners were normal. However, the couple were never screened for haemoglobinopathies.
During the interview, possible theoretical reasons for the implantation failure were discussed and potential beneficial role of intra venous immunoglobulin (IVIG) was appraised. This was emphasized to the couple that neither the cause of implantation failure nor the efficacy of IVIG in its prevention is clearly established at present. They were counselled about the possible side effects of IVIG and given time to make an informed decision as to the trial of IVIG therapy in their ICSI / ET treatment cycle.
The couple had already undergone four cycles of ovarian
They were advised haemoglobin electrophoresis to rule 57
Apollo Medicine, Vol.1 September 2004
Brief Report
out thalassemia / sickle cell abnormality. As the couple had come to India on a short vacation, they requested to start the treatment immediately.
Chorionic villous sampling was performed at 11 weeks gestation, which reported the fetus to have sickle cell trait only. Antenatal period of the patient was uneventful. She delivered a healthy, female baby of 3 kg weight at term by elective LSCS due to high head and patient’s reluctance to try for the vaginal delivery.
Pituitary down regulation was achieved by subcutaneous Buserelin acetate 0.5 mg once daily (Suprefact; Aventis Pharma, Germany) commencing on Day 21 of the cycle using long protocol regime. Following this controlled ovarian hyper stimulation was initiated with recombinant FSH (Gonal-F; Sereno, Italy) 150 IU daily and follicular growth and endometrial development were monitored using transvaginal ultrasonography. On day 11 of the FSH therapy more than three leading follicles of 18-20 mm diameter with an endometrial thickness of 9 mm were observed on ultrasonography. Transvaginal colour Doppler studies demonstrated good perifollicular vessels, low resistance flow in bilateral uterine arteries (RI - Resistive Index 0.6) and the presence of endometrial vessels up to the inner layer (zone 3 as defined by Apple Baum) [2]. Injection HCG (Profasi; Serono, Italy) 10,000 IU was administered and 34 hours later 18 oocytes were retrieved by transvaginal ultrasound guided follicular aspiration. Prophylactic human albumin 20% (Zenalb 20 – Bio Products Laboratory, UK) 200 mL intravenously was given to the patient during the oocyte retrieval procedure in view of the number of follicles and her previous history of severe OHSS.
DISCUSSION Assisted reproductive techniques such as IVF, ICSI and ET are now widely available for the infertile couples. Despite significant improvement in the success rates, unexplained repeated (three or more attempts) implantation failure of good quality embryos remains a frustrating, unsolved mystery. Various research studies have indicated that endometrial receptivity involves both hormonal and immunological factors [3]. However, the roles that allo immunity and auto immunity may play in reproductive failure, have not been clearly established. Several immune tests (anti phospholipid antibodies, anti nuclear antibody, Lupus anticoagulant, natural killer cells, leucocyte antibodies) are available but controversy still exists on their precise role in such cases. Even when all conventional immune tests are negative as in this case, patients may face repeated reproductive failure. Intravenous immunoglobulins, first given to the recurrent aborters with anti-phospholipid syndrome, have been administered to the unexplained repeated aborters and IVF / ET failures with variable results and controversial opinions [3-5-8]. IVIG is purified, concentrated immunoglobulin G antibodies pooled from human blood donors. Due to its strong “immunomodulating” effect in several well established disorders, high - dose intravenous immunoglobulin (IVIG) has been proposed and used as an alternative for immunotherapy with allogenic leucocytes, in patients with unexplained recurrent spontaneous abortion [4]. IVIG reduces the activation of natural killer cells (NK cells) and NK killing activity both in vitro and in vivo. These NK cells are present within the decidua and play a crucial role in successful implantation [3]. Studies have been reported showing improved success rate in IVF cycles with the use of high dose IVIG [5,3,6] as found in this case, while other reports have shown no benefit [7,8]. Although IVIG is usually well tolerated by the patients, the occurrence of major and minor side effects is uncommon and infectious morbidity is low [9], however, in the absence of data from the large controlled trials, its use is still regarded as experimental and proper informed consent of the patient is essential.
All oocytes were subjected to micromanipulation technique - ICSI. Fertilization was achieved in 9 of these and 48 hours later four embryos (grade I × 2, grade II × 2) were transferred into the uterine cavity. Having obtained the couple’s written consent, intravenous immunoglobulin (Sandoglobulin; Novartis, UK) was given to the patient at a dosage of 400 mg / kg prior to the ET. Luteal support was initiated in the form of micronized vaginal progesterone (Susten; Sun Pharma, India) 400 mg twice daily. The couple were although advised and repeatedly reminded to have Hb Electrophoresis since their first visit but they produced the test report only on the day of ET. Both partners tested to be positive for the sickle cell trait. They were counselled in detail and made aware that a chorionic villous sampling (CVS) would be recommended if pregnancy is achieved. On day 10 - post embryo transfer, patient developed moderate OHSS requiring hospitalization. Her condition was monitored closely and managed conservatively using intravenous normal saline, albumin, low molecular weight (LMW) Heparin and ascitic fluid paracentesis twice. Her serum hCG measurements on day 14 and 16 confirmed successful implantation and an ultrasound 4 weeks post ET demonstrated a singleton live intrauterine pregnancy. Her OHSS settled completely by this time and she was discharged home. IVIG was repeated once more 4 weeks after the first administration at the same dosage. Apollo Medicine, Vol. 1, September 2004
Severe OHSS is a potentially life threatening complication not uncommonly seen in PCOS patients undergoing ovarian stimulation using Gonadotrophins, the reported incidence in literature varies between 6-60 % [10] . The exact mechanism responsible is unknown, the most widely accepted hypothesis 58
Brief Report
is that it originates from increased capillary permeability leading to extravasation of fluid - firstly into the ovary and than into the abdominal cavity [11]. OHSS is four times more likely to occur in conception cycles [12]. Albumin infusion at the time of oocyte retrieval has been suggested to be a successful prophylactic measure against the development of OHSS [13] but the efficacy has not been confirmed by more recent studies.
Obstet Gynecol Surv 1989; 44: 430-440. 2. Applebaum M. The uterine biophysical profile. Ultrasound Obstet Gynecol 1995 ; 5: 67-6 8. 3. Coulam CB, Goodman C. Increased pregnancy rates after IVF /ET with intravenous immunoglobulin treatment in women with elevated circulating C56 + cells. Early Pregnancy 2000 Apr; 4(2): 90-98. 4. Mueller-EcKhardt G. Immunotherapy with intravenous immunoglobulin for prevention of recurrent pregnancy loss : American Journal of Reproductive Immunology. 1994 Dec.; 32(4): 281-285.
In the case reported, there was a definite history of severe OHSS during the patient’s first IVF cycle immediately after oocyte retrieval. Prophylactic albumin infusion at the time of oocyte retrieval therefore was given which may have prevented the occurrence of OHSS initially however as soon as successful implantation started (day 10 post ET) patient did develop severe OHSS for which the patient was hospitalised and managed conservatively successfully.
5. Coulam CB, Krysa LW, Bustillo M. Intravenous immunoglobulin for in-vitro fertilization failure. Human Reproduction 1994 Dec; 9(12): 2265-2269. 6. Scher J, Salazar C. Clinical experience with IVIG Rx in patients with prior failed IVF pregnancies: report of 30 consecutive patients. Am J Reprod. Immunol. 2000 Aug; 44(2): 121-124.
Haemoglobinopathies are not uncommon in Indian origin population with a reported incidence of sickle cell disorder as 4.3% [14]. The clinical disease requires a double dose of the abnormal gene for expression of the clinical disease (homozygosity for the βs gene). Therefore, if both partners have sickle cell trait, the offspring will have 25% chance of having clinical sickle cell disease. The cardinal features of the disease include chronic haemolytic anaemia and recurrent painful episodes.
7. Balash J, Creus M, Fabregues F, Font J, Martorell J, Vanrell JA. Intravenous immunoglobulin preceding in vitro fertilization - embryo transfer for patients with repeated failure of embryo transfer. Fertil Steril 1996 March; 65(3): 655-658. 8. Stephenson MD, Fluker MR. Treatment of repeated unexplained in-vitro-fertilization failure with intravenous immunoglobulin: A randomised, placebo controlled Canadian trial. Fertil Steril 2000 Dec; 74(6): 1108-1113. 9. AL Clark. Clinical uses of intravenous immunoglobulin in pregnancy. Clinical Obstetrics & Gynecology 1999 June; 42(2): 368-380.
Although this patient had undergone several years of infertility treatment at various parts of the world, haemoglobinopathy screening was never done. When the couple were eventually advised the screening, they did not comply with the instructions until quite late. Were the couple diagnosed to have sickle cell trait earlier, they would have had the option of considering pre-implantation genetic diagnosis (PGD) in embryos using polymerase chain reaction (PCR) assay and that would have avoided the stress and anxiety they went through while waiting for the results of chorionic villous sampling. Fortunately, the report was favourable, hence they could continue the pregnancy and had the ultimate joy of having a healthy child.
10. Rizk B. Ovarian hyperstimulation syndrome. Progress in Obstetrics & Gynaecology 1994; 11; 311-349. 11. McManus Joanne, McClure Neil. Complications of assisted reproduction. The Obstetrician & Gynaecologist July 2002; 4(3); 124-128. 12. Haning RV, Strawn EY, Nolten WE. Pathophysiology of the ovarian hyper stimulation syndrome. Obstet Gynecol 1985 ; 66 : 22-24. 13. Asch RH, Ivery G, Goldsman M, Frederick JL, Stone SC, Balmaceda JP. The use of intravenous albumin in patients at high risk for severe ovarian hyper stimulation syndrome. Hum Reprod 1993; 8 :1015-1020.
REFERENCES
14. Balgir RS. Genetic epidemiology of the three predominant abnormal hemoglobins in India. J Assoc Physicians India 1996 Jan; 44(1) : 25-28.
1. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyper stimulation syndrome: an update review.
59
Apollo Medicine, Vol. 1, September 2004