Journal of Human Reproductive Science
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Year : 2018  |  Volume : 11  |  Issue : 1  |  Page : 75-78

Live birth after rescue in vitro maturation–intracytoplasmic sperm injection in type 1 diabetes, polycystic ovary syndrome patient using clomiphene–antagonist protocol

Department of IVF and Genetics, Srushti Fertility Centre and Women's Hospital, Chennai, Tamil Nadu, India

Date of Web Publication27-Mar-2018

Correspondence Address:
M Elanchezhian
#2, Dhandayuthapani Nagar, 2nd Street, Kotturpuram, Chennai - 600 085, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jhrs.JHRS_65_17

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Infertility in patients with polycystic ovary syndrome (PCOS) associated with diabetes leads to challenging situations seeking alternative treatments. In vitro maturation (IVM) followed by intracytoplasmic sperm injection (ICSI) could overcome the challenges with promising pregnancies in such patients. In the treatment of a 32-year-old diabetic woman who also had PCOS, single immature oocyte was retrieved. Rescue IVM followed by ICSI yielded a grade 1 day 3 embryo which on transferring resulted in pregnancy and a healthy infant was delivered. Rescue IVM–ICSI could help in achieving pregnancy and live birth. Stimulation involving clomiphene and gonadotropin-releasing hormone antagonist is an effective and patient-friendly protocol for women with PCOS and diabetes and also for poor responders.

Keywords: Clomiphene, diabetes, in vitro fertilization, in vitro maturation, polycystic ovary syndrome

How to cite this article:
Sankari S, Elanchezhian M, Selvamani D, Nagarajan M, Gopikrishnan D. Live birth after rescue in vitro maturation–intracytoplasmic sperm injection in type 1 diabetes, polycystic ovary syndrome patient using clomiphene–antagonist protocol. J Hum Reprod Sci 2018;11:75-8

How to cite this URL:
Sankari S, Elanchezhian M, Selvamani D, Nagarajan M, Gopikrishnan D. Live birth after rescue in vitro maturation–intracytoplasmic sperm injection in type 1 diabetes, polycystic ovary syndrome patient using clomiphene–antagonist protocol. J Hum Reprod Sci [serial online] 2018 [cited 2023 Mar 24];11:75-8. Available from:

   Introduction Top

Infertility is an increasing problem in both developed and developing countries, with up to one in six couples requiring treatments.[1] Polycystic ovary syndrome (PCOS) is present in almost one of every four women with type 1 diabetes.[2] The major risk factors for infertility related to diabetes mellitus are hyperandrogenism and PCOS in women.

Conventional stimulation protocol in spite of its higher pregnancy rates increases the risk of ovarian hyperstimulation syndrome (OHSS), multiple gestations, etc., The need for simpler protocols with low risks, low cost, and maximum singleton pregnancies could be achieved by modifying stimulation protocols.

The present case highlights the successful treatment for infertility of type 1 diabetic PCOS patient using clomiphene–antagonist protocol followed by rescue in vitro maturation (IVM)–intracytoplasmic sperm injection (ICSI) procedures.

   Case Report Top

A 32-year-old woman and her 35-year-old husband presented in 2016 with a 5-year history of primary infertility and two failed attempts of conventional in vitro fertilization (IVF)/ICSI. The female was a type 1 diabetic patient and the existence of bilateral polycystic ovaries was discovered by ultrasound examination. The findings of hysteroscopy were normal and the hormonal parameters were as expected (follicle-stimulating hormone [FSH]: 7.40 mIU/ml, luteinizing hormone: 9.89 mIU/ml, and prolactin: 15.84 ng/ml). The semen analysis showed normal semen parameters. The chromosomal analysis showed normal male and female karyotypes.

The female started an IVF program in which she was given clomiphene tablets orally for the first 5 days, and from day 7 to 13, 150 IU of recombinant FSH was administered subcutaneously. From day 8 to 14, 150 IU of menotropin and from day 10 to 14, 0.25 mg of cetrorelix were administered subcutaneously. The patient was evaluated continuously, and when leading follicle of 20 mm (only follicle) on day 15 was observed, 250 μg recombinant human chorionic gonadotropin-alpha was administered subcutaneously for triggering. After 36 h, one oocyte was collected which was found to be immature [Figure 1] (germinal vesicle stage) when denuded. The denuded oocyte was subjected to rescue IVM for 25 h (until the extrusion of the first polar body) in culture medium (Vitrolife ®, Goteborg, Sweden). The matured oocyte [Figure 2] (metaphase II) was injected with the husband sperm after processing the semen by swim-up method. Two pronuclei [Figure 3] were seen 18 h post-ICSI and a grade 1 embryo [Figure 4] was generated on day 3. A successful pregnancy was achieved. Fetal cardiac activity was noted from 6 weeks' gestational age. The patient developed gestational hypertension which along with the diabetes was managed optimally with antihypertensives and insulin, respectively. As the patient developed preeclampsia at 32 weeks, pregnancy was terminated by a safe cesarean section and a healthy male infant (birth weight 2200 mg) was delivered.
Figure 1: Obtained germinal vesicle oocyte after denudation

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Figure 2: MII oocyte after in vitro maturation

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Figure 3: Two pronuclei stage

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Figure 4: Transferred day 3 embryo

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   Discussion Top

Diabetes mellitus in female is associated with disturbed ovarian function, but strict metabolic control may encourage the resumption of ovulation and allow ovarian stimulation for assisted reproductive technology.[3] The protocol involving clomiphene citrate (CC), human menopausal gonadotropin (hMG), and cetrorelix helps women with PCOS as the incidences of moderate and severe OHSS are reduced.[4] It is evident that CC/hMG protocol has resulted in a significantly lower incidence of severe OHSS when compared to GnRA long protocol.[5] Moreover, it was also suggested that protocol involving gonadotropin-releasing hormone (GnRH) antagonist plus mild doses of exogenous gonadotropins and oral compounds such as CC or aromatase inhibitors was more patient friendly.[6] Similarly, a chronic low-dose regiment of gonadotropins in PCOS patients has completely eliminated the troublesome complications of OHSS and also reduced the multiple pregnancy rates to a reasonable minimum.[3],[7] Therefore, modifications in stimulation protocol for patients with PCOS can overcome the risks of OHSS, and the side effects are less as the medication is administered only for a few days.

A pregnancy using immature oocytes in nonstimulated cycles was achieved, in 1994, where the IVM period was 43–54 h.[8] In another study, oocytes retrieved using nonstimulated cycles were in vitro maturated for 24–48 h.[9] Hence, IVM requires the maturation of oocytes in the laboratory for ≥24 h before insemination, and there is a need for monitoring maturity of immature oocytes periodically during the maturation time.[10],[11]

Characteristic features of PCOS such as hyperandrogenism, obesity, insulin resistance, and metabolic abnormalities may contribute to the increased risks of obstetrical and neonatal complications, and those patients are prone to pregnancy-induced hypertension, preeclampsia, and preterm birth suggesting cesarean section.[12],[13]

There are many reports on successful live births using IVM–IVF procedures that have ~ 50% maturation rates and ~ 60% fertilization rates, but the number of live births was comparatively low.[14],[15],[16],[17],[18] A pregnancy rate of 27.1% was achieved after IVM–IVF by transferring 6.3 embryos per patient.[19]

   Conclusion Top

Rescue IVM–ICSI is an important tool at certain circumstances in the treatment of women with PCOS and diabetes which can result in pregnancy and live birth. It is also acceptable that the modified approach involving GnRH antagonist, CC, and hMG is an effective ovarian stimulation protocol which also holds good with poor responder women and serves as a patient-friendly protocol as duration of gonadotropin injection is shorter.[20]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, et al. Insulin dependant diabetes mellitus: Implications for male reproductive function. Hum Reprod 2007;22:1871-7.  Back to cited text no. 1
Escobar-Morreale HF, Roldán-Martín MB. Type 1 diabetes and polycystic ovary syndrome: Systematic review and meta-analysis. Diabetes Care 2016;39:639-48.  Back to cited text no. 2
Taylor CT. Review: Diabetes and assisted reproductive technology. Br J Diabetes Vasc Dis 2002;2:247-53.  Back to cited text no. 3
Lin YH, Seow KM, Hsieh BC, Huang LW, Chen HJ, Huang SC, et al. Application of GnRH antagonist in combination with clomiphene citrate and hMG for patients with exaggerated ovarian response in previous IVF/ICSI cycles. J Assist Reprod Genet 2007;24:331-6.  Back to cited text no. 4
MacDougall MJ, Tan SL, Jacobs HS.In vitro fertilization and the ovarian hyperstimulation syndrome. Hum Reprod 1992;7:597-600.  Back to cited text no. 5
Fauser BC, Nargund G, Andersen AN, Norman R, Tarlatzis B, Boivin J, et al. Mild ovarian stimulation for IVF: 10 years later. Hum Reprod 2010;25:2678-84.  Back to cited text no. 6
Homburg R, Howles CM. Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: Rationale, results, reflections and refinements. Hum Reprod Update 1999;5:493-9.  Back to cited text no. 7
Trounson A, Wood C, Kausche A.In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients. Fertil Steril 1994;62:353-62.  Back to cited text no. 8
Le Du A, Kadoch IJ, Bourcigaux N, Doumerc S, Bourrier MC, Chevalier N, et al.In vitro oocyte maturation for the treatment of infertility associated with polycystic ovarian syndrome: The french experience. Hum Reprod 2005;20:420-4.  Back to cited text no. 9
Gunasheela S, Gunasheela D, Gupta S, Peter J. Conventional stimulation protocol failed to produce mature oocytes: Rescue IVM resulted in six pregnancies after in vitro fertilization and embryo transfer. J Exp Sci 2011;2:14-6.  Back to cited text no. 10
Jurema MW, Nogueira D.In vitro maturation of human oocytes for assisted reproduction. Fertil Steril 2006;86:1277-91.  Back to cited text no. 11
Pelinck MJ, Vogel NE, Hoek A, Arts EG, Simons AH, Heineman MJ, et al. Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: A pilot study. Hum Reprod 2005;20:642-8.  Back to cited text no. 12
Palomba S, de Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC, et al. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update 2015;21:575-92.  Back to cited text no. 13
Barnes FL, Kausche A, Tiglias J, Wood C, Wilton L, Trounson A, et al. Production of embryos from in vitro-matured primary human oocytes. Fertil Steril 1996;65:1151-6.  Back to cited text no. 14
Chian RC, Buckett WM, Tulandi T, Tan SL. Prospective randomized study of human chorionic gonadotrophin priming before immature oocyte retrieval from unstimulated women with polycystic ovarian syndrome. Hum Reprod 2000;15:165-70.  Back to cited text no. 15
Lin YH, Hwang JL, Huang LW, Mu SC, Seow KM, Chung J, et al. Combination of FSH priming and hCG priming for in vitro maturation of human oocytes. Hum Reprod 2003;18:1632-6.  Back to cited text no. 16
Nagele F, Sator MO, Juza J, Huber JC. Successful pregnancy resulting from in vitro matured oocytes retrieved at laparoscopic surgery in a patient with polycystic ovary syndrome: Case report. Hum Reprod 2002;17:373-4.  Back to cited text no. 17
Son WY, Yoon SH, Park SJ, Yoon HJ, Lee WD, Lim JH, et al. Ongoing twin pregnancy after vitrification of blastocysts produced by in vitro matured oocytes retrieved from a woman with polycystic ovary syndrome: Case report. Hum Reprod 2002;17:2963-6.  Back to cited text no. 18
Cha KY, Han SY, Chung HM, Choi DH, Lim JM, Lee WS, et al. Pregnancies and deliveries after in vitro maturation culture followed by in vitro fertilization and embryo transfer without stimulation in women with polycystic ovary syndrome. Fertil Steril 2000;73:978-83.  Back to cited text no. 19
Mohsen IA, Youssef MA, Elashmwi H, Darwish A, Mohsen MN, Khattab SM. Clomiphene citrate plus modified GnRH antagonist protocol for women with poor ovarian response undergoing ICSI treatment cycles: Randomized controlled trial. Gynecol Obstet 2013;3:158.  Back to cited text no. 20


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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