Fertility Preservation in Turner Syndrome

Karyotype Does Not Predict Ovarian Response to Stimulation

Julia Vergier; Pauline Bottin; Jacqueline Saias; Rachel Reynaud; Catherine Guillemain; Blandine Courbiere

Clin Endocrinol. 2019;91(5):646-651.

Conclusion

For TS young women with spontaneous menarche, early fertility counselling is advised as soon as possible and prior to time-related DOR. Ovarian reserve testing and feasibility of oocyte cryopreservation must be discussed during the transition from paediatric to adulthood. Blood karyotype does not seem to be the best marker to predict ovarian response to stimulation. Antral follicular count, AMH level and baseline FSH level seem to have a better prognostic significance, but larger cohort studies are needed in order to confirm these facts. Finally, no pregnancy in women with TS has been described using frozen-thawed oocytes; therefore, FP benefits and ideal age for deciding the best moment for a FP in still menstruated TS women with normal AMH are yet to be determined. Given the paucity of data, the creation of an international register of FP attempts assisted medical reproduction techniques and following outcome in TS women would be opportune.

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Abbreviations
AFC, antral follicular count; AMH, anti-müllerian hormone; COS, controlled ovarian stimulation; DOR, diminished ovarian reserve; FISH, fluorescent in situ hybridization; FP, fertility preservation; IVF, in vitro fertilization; MII, metaphase II oocytes; OTC, ovarian tissue cryopreservation; PCOS, polycystic ovarian syndrome; POF, premature ovarian failure; TS, Turner syndrome.

Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.

Table 1. Description of the women undergoing controlled ovarian stimulation
	Patient 1	Patient 2	Patient 3
Karyotype	46,XX,del(Xp11.4)	45,X Monosomy (100/100)	Mosaicism 46,XX 83%; 45,X 9%; 46 XderX 8%
Age at TS diagnosis (years)	20	12	9
Diagnosis circumstances	Secondary amenorrhoea	Growth retardation	Growth retardation
Puberty	Spontaneous at 13	Spontaneous at 11	Spontaneous
Menarche	Spontaneous at 14 Secondary amenorrhoea at the age of 20	Spontaneous at 12 Regular menstruations	Spontaneous at 13 Secondary amenorrhoea at the age of 17
Age at fertility evaluation (years)	27	26	17
Body mass index (kg/m²)	20.57	20.82	18.49
Baseline serum FSH (IU/L)	10	6.5	5.9
Serum AMH (pmol/L)	3.6	62.9	95.0
Antral follicle count	6	18	PCOS
Other Turner conditions	0	Growth retardation treated with rGH Hypothyroid supplemented	Growth retardation treated with rGH Bicuspid aortic valve Mild and stable aortic root dilation

Abbreviation: PCOS, Polycystic ovarian syndrome.

Table 2. Description of ovarian stimulation cycles
	Patient 1			Patient 2	Patient 3
	Cycle 1	Cycle 2	Cycle 3	Patient 2	Patient 3
Age at stimulation	28	28	30	25	18
Protocol	Antagonist	Antagonist	Antagonist	Antagonist	Antagonist
Duration of stimulation (days)	9	7	11	8	9
Total gonadotropin stimulation dose (IU)	2700	2100	4950	2700	1575
Trigger day E2 levels (pg/mL)	57	79	111	952	3549
Total number of oocytes retrieved	3	3	7	20	25
Number of mature oocytes vitrified (MII)	2	2	5	17	20

Table 3. Review of oocyte vitrification in TS women
Study	Peripheral blood karyotype	Age at ovarian stimulation	Baseline FSH (IU/L)	AMH (pmol/L)	AFC Count	Number cryopreserved oocytes
Kavoussi et al²⁶	NA	28	4.3	NA	40	13
Lau et al²⁷	45,X(98)/47,XXX(2)	16	6.3	NA	6	2
Balen et al²³	45,X(28/30)/46,XX(2/30)	28	3.3 but 3 y before COS	43.8 pmol/L	NA	3 cycles: 9, 7, 20
El-Shawarby et al²⁸	45,X(86)/47,XXX(11)/46,XX(3)	22	4.6	8.52 pmol/L	7	8
Oktay et al¹⁸	45,X(27/30)/47,XXX(3/30)	13	5.7	11.36 pmol/L	6	9 + 1 (IVM)
	46,XX(11/20)/45,X(9/20)	14	5.3	6.4/12.1 pmol/L (2 cycles, year-on-year)	12	8 for the first cycle, and 4 for the second
	46,XX(16/20)/45,X(4/20)	13	5.6	5.43 pmol/L	6	7 + 5 (IVM)
Talaulikar et al¹⁹	45,X(100)	22	6.9	3.5 pmol/L	7	9
	45,X(83)/46,XX(17)	18	3.2	3.05 pmol/L	9	13
	45,X(61)/46,XX(39)	18	7.4	7 pmol/L	11	9
	45,X/46,XX/47,XXX	25	2.9	9.5 pmol/L	12	10
	45,X(63)/46,XX(37)	21	6.2	3.5 pmol/L	5	4
	45,X(50)/46,XX(50)	22	8.4	21.3 pmol/L	14	6
	45,X(88)/46,XX(12)	26	7.5	12.1 pmol/L	11	12