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Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 96-98

Fertility preservation in a premenarcheal female with sickle cell anemia

Reproductive Medicine Unit, Artemis Health Institute, Gurgaon, Haryana, India

Date of Web Publication22-Feb-2019

Correspondence Address:
Sonu Balhara Ahlawat
Artemis Health Institute, Sector 51, Gurgaon - 122 001, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tofj.tofj_7_18

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The objective of the study was fertility preservation in a premenarcheal female with sickle cell anemia (SCA) using controlled ovarian hyperstimulation and oocyte preservation. The study design was a case report. The study was conducted at the reproductive medicine unit of a tertiary care private hospital. A 15-year-old premenarcheal female with Tanner stage 3 breast development and Tanner stage 1 pubic hair diagnosed with SCA, referred by a medical oncologist for fertility preservation before undergoing chemotherapy and bone marrow transplant. The interventions were evaluation of ovarian reserve, ovarian stimulation (OS), transvaginal oocyte aspiration, and oocyte cryopreservation (OC). The main outcome measure was cryopreservation of mature oocytes before the antineoplastic therapy. Controlled ovarian hyperstimulation allowed for cryopreservation of ten mature oocytes before the start of the patient's gonadotoxic treatment. OS and OC can be successfully performed in premenarcheal/peripubertal SCA patients before undergoing chemotherapy, thus providing a viable option for fertility preservation.

Keywords: Fertility preservation, oocyte cryopreservation, premenarcheal, sickle cell anemia

How to cite this article:
Ahlawat SB, Singh S. Fertility preservation in a premenarcheal female with sickle cell anemia. Onco Fertil J 2018;1:96-8

How to cite this URL:
Ahlawat SB, Singh S. Fertility preservation in a premenarcheal female with sickle cell anemia. Onco Fertil J [serial online] 2018 [cited 2020 Feb 26];1:96-8. Available from: http://www.tofjonline.org/text.asp?2018/1/2/96/252692

  Introduction Top

Sickle cell disease is an inherited disorder. It is a major cause of morbidity and mortality with reduced life expectancy. Allogenic hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for this disease. When employed, HSCT is typically undertaken early in the course of the disease and hence at a younger age, before the onset of irreversible organ damage. HSCT involves conditioning and immunosuppressive chemotherapy to suppress the patient's bone marrow. The conventional myeloablative regimes for HSCT typically include gonadotoxic alkylating agents such as busulfan and cyclophosphamide. Therefore, this potentially lifesaving treatment carries a high risk of inducing infertility and 80% risk of premature ovarian insufficiency in young affected females. Thus, these patients are frequently referred for fertility preservation before undergoing HSCT.

The different options for fertility preservation in females currently available are embryo preservation, oocyte preservation, and ovarian tissue preservation. Ovarian tissue freezing is the currently favored treatment modality for fertility preservation in young premenarchal and prepubertal girls. Then again, the available techniques for cryopreservation of ovarian tissue are still experimental.[1] Techniques for oocyte cryopreservation (OC) have seen dramatic improvement in the last decade with improved pregnancy outcomes. Considering accumulated evidence in recent years, OC coupled with pregnancy rates, the procedure is no longer viewed as experimental in adult patients. Hence, OC has long been included as part of standard assisted reproductive treatment practices in adults.[2] However, to implement the same in adolescent and or teenage girls, further evidence is needed.

Ovarian tissue cryopreservation (OTC) has been implemented with increasing frequency for this young population, but the efficacy of this practice is far from proven. Few pregnancies after OTC have been reported in,[3],[4],[5],[6] and in several cases, the provenance of such pregnancies has remained unclear, as in some cases endogenous ovarian function within remaining ovarian tissue may have returned.[7] Due to the sexual immaturity of the pediatric population, it has been suggested that controlled ovarian stimulation (COS) may be ineffective.[8]

The current paper presents a case of successful COS and OC of ten mature oocytes in a premenarchal, prepubertal female with sickle cell anemia (SCA).

  Materials and Methods Top

A 15-year-old patient presented to the pediatric hematology-oncology unit for HSCT as she was a known case of SCA since the age of 6 months.

Physical evaluation of the patient revealed a thin built tall premenarchal girl with Tanner stage 3 breast development and Tanner stage 1 pattern of pubic hair. She weighed 42 kg and attained height of 147 cm. Pelvic examination revealed partially intact hymen and grossly normal anatomy.

Transabdominal ultrasonography revealed a small uterus with an endometrial thickness of 3.0 mm. Both ovaries were normal in size and echo pattern with an antral follicle count of five on the left side and four on the right side of size <10 mm. There was no significant free fluid detected. Hormonal assessment detected an anti-Mullerian hormone level (AMH) of 3.43 ng/ml.

OTC was discussed with the patient and her parents. The current experimental nature and pregnancy rates reported in literature were discussed. The patient was not willing to undergo any surgical procedure and wanted to know if there was any other viable option. OC was discussed keeping in mind her disease and the effect COS might have on the patient due to SCA. A multidisciplinary approach was taken, and her hematologist was actively involved in the decision making and fertility preservation process.

Keeping in mind that the hypothalamic–pituitary–ovarian (HPO) axis may not be optimized at this stage, it was decided to stimulate with a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Ovarian stimulation (OS) was started with a dose of 225 IU of Menopur (human menopausal gonadotropin by Ferring Pharmaceutical). GnRH antagonist was started when the lead follicle was 13 mm, which was on the 8th day of stimulation. Follicular monitoring was carried out by serial transabdominal ultrasonography. Ovulation trigger was given with human chorionic gonadotropin after 13 days of stimulation and a dose of 10000 IU was given, when three lead follicles were ≥18 mm in size, with an estradiol concentration of 2301 pg/ml. The patient was admitted 1 day before her oocyte retrieval for preoperative optimization. Transvaginal ultrasound-guided oocyte collection under general anesthesia was performed using a 17 gauze (cook) single lumen needle, 36 h after the trigger. An aspiration pressure of 100 mmHg was used.

  Results Top

During the procedure, a total of 11 oocytes were retrieved. The oocytes were incubated for 3 h post retrieval. The oocytes were denuded, and 10 M-II oocytes were obtained. Kitazato media and protocol were used for oocyte vitrification. The oocytes were exposed to increasing concentration of equilibration solution (for about 15 min) and then exposed to vitrification solution for 90 s. Then, they were loaded on cryolocks (two cryolocks loaded with three oocytes each and two cryolocks loaded with two oocytes). These were directly plunged in liquid nitrogen at −196°C and stored in cryocontainer. The patient tolerated the procedure well. She was discharged the next day and called for follow-up on day 4. Transabdominal sonography revealed minimal free fluid, and she was reported as symptom-free.

One week after oocyte aspiration, the patient initiated multidrug chemotherapy with fludarabine, cyclophosphamide, and azathioprine (immunosuppressive chemotherapy). At the time of this report, it has been 58 days after the patient's oocyte pick-up (OPU), and she is undergoing immunosuppressive chemotherapy. Hormone assessment 1 month after OPU revealed AMH 1.4 ng/ml, FSH 1.83 mIU/ml, and LH 0.84 mIU/ml.

  Discussion Top

This case report describes one of the few successful OCs after COS in a pediatric SCA patient who has not achieved puberty. It is believed that prepubertal and/or premenarcheal patients may not be responsive to OS due to their immature HPO axis. Thus, there are very few cases of premenarcheal OS reported in the literature.

At present, the method of choice for preserving fertility in this age group is OTC, but it is still considered experimental and involves surgery. As the patient is a premenarcheal, embryo cryopreservation is not a feasible treatment option. In contrast, OC has good results in terms of cryosurvival and live birth rates and could be the method of choice if feasible in this group of patients also.[8] Compared to OTC, approximately 1000 births have been reported from OC without any congenital abnormalities.[9] Reports of successful pregnancies from cryopreserved ovarian tissue and oocytes in a premenarchal girl and a teenager, respectively,[6],[10] infer the competence of these procedures in preserving the fertility in premenarcheal cases with SCA.


SBH acknowledges Dr. Gaurav Khare, Senior Consultant and Head, Pediatric Hematology and Oncology, Immunology and Bone Marrow Transplant, for referring the case for possible fertility preservation consultation, and Dr. Nalini Mahajan, Director Mother and Child Hospital, New Delhi, and Artemis Health Institute, Gurgaon, for the encouragement.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Fertility preservation and reproduction in patients facing gonadotoxic therapies: An ethics committee opinion, Ethics Committee of the American Society for Reproductive Medicine American Society for Reproductive Medicine, Birmingham, Alabama. Fertil Steril 2018;110.  Back to cited text no. 1
Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:2500-10.  Back to cited text no. 2
Callejo J, Salvador C, González-Nuñez S, Almeida L, Rodriguez L, Marqués L, et al. Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors. J Ovarian Res 2013;6:33.  Back to cited text no. 3
Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Sanchez Serrano M, Schmidt KT, et al. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: A review of 60 cases of reimplantation. Fertil Steril 2013;99:1503-13.  Back to cited text no. 4
Meirow D, Ra'anani H, Biderman H. Ovarian tissue cryopreservation and transplantation: A realistic, effective technology for fertility preservation. Methods Mol Biol 2014;1154:455-73.  Back to cited text no. 5
Demeestere I, Simon P, Dedeken L, Moffa F, Tsépélidis S, Brachet C, et al. Live birth after autograft of ovarian tissue cryopreserved during childhood. Hum Reprod 2015;30:2107-9.  Back to cited text no. 6
Donnez J, Silber S, Andersen CY, Demeestere I, Piver P, Meirow D, et al. Children born after autotransplantation of cryopreserved ovarian tissue. A review of 13 live births. Ann Med 2011;43:437-50.  Back to cited text no. 7
Lawrenz B, Rothmund R, Neunhoeffer E, Huebner S, Henes M. Fertility preservation in prepubertal girls prior to chemotherapy and radiotherapy – Review of the literature. J Pediatr Adolesc Gynecol 2012;25:284-8.  Back to cited text no. 8
Noyes N, Porcu E, Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online 2009;18:769-76.  Back to cited text no. 9
Kim TJ, Hong SW. Successful live birth from vitrified oocytes after 5 years of cryopreservation. J Assist Reprod Genet 2011;28:73-6.  Back to cited text no. 10


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