Feasibility and efficiency of delayed ovarian stimulation and oocyte banking for fertility preservation after fertility-impairing treatment

doi:10.21203/rs.3.rs-2499435/v1

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Feasibility and efficiency of delayed ovarian stimulation and oocyte banking for fertility preservation after fertility-impairing treatment

https://doi.org/10.21203/rs.3.rs-2499435/v1

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published 20 Sep, 2023

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Purpose

The aim of our study was to evaluate the feasibility and efficiency of delayed ovarian stimulation and oocyte banking for fertility preservation after fertility-impairing treatment regardless of the initial disease.

Methods

We conducted a cohort study based on population of women < 40 years of age with diminished ovarian reserve (n = 129). Three groups of women were compared according to the type of initial disease: hematological malignancies, solid tumors, and benign diseases. The endpoints were the number of metaphase II oocytes collected per woman, whether vitrified or immediately used in in vitro fertilization and the cumulative live birth rate per stimulation cycle.

Results

We studied 245 delayed controlled ovarian stimulation cycles in 129 women: 201 for fertility preservation and 44 for in vitro fertilization and fresh embryo transfers. The number of metaphase II oocytes collected per woman after oocyte banking was similar in the three groups, with a mean of 10.7 ± 4.6, 12.3 ± 9.1 and 10.1 ± 7.6 oocytes (NS), respectively. The cumulative live birth rate was 38%, with 8 live births for the 21 women who wanted to conceive.

Conclusion

After fertility-impairing treatment, practitioners should discuss a fertility preservation procedure for banking oocytes, even if a fertility preservation has already been performed.

Health sciences/Urology/Gonads/Ovary

Health sciences/Health care/Quality of life

Health sciences/Oncology/Cancer

Health sciences/Diseases/Reproductive disorders/Infertility

fertility preservation

oncofertility

fertility-impairing treatment

diminished ovarian reserve

oocyte cryopreservation

Since ovarian reserve diminishes progressively throughout the reproductive life span until menopause, any iatrogenic damage to the ovarian reserve may lead to premature ovarian insufficiency (POI) and infertility [1]. Emergency fertility preservation (FP) of germinal tissue or oocytes should be proposed when benign or malignant disease or therapy is likely to impair ovarian reserve [2]. Since the development of vitrification, oocyte cryopreservation is the method advised for most women undergoing FP for medical indications [3].

Unfortunately, for various reasons (the time between diagnosis and the start of treatment, refusal of a woman to undergo additional therapy, emergency adnexectomy, lake to referral to FP center, etc.), emergency FP before definitive impairment of the ovarian reserve is not always possible, as for example, for borderline ovarian tumors [4]. Sometimes, the number of cryopreserved oocytes in emergency before fertility-impairing treatment is too small to give a likelihood of childbearing. When oocyte cryopreservation is performed before 35 years of age and before cancer treatment, the cumulative live birth rate (CLBR) is only 9.1% (CI -0.7-19) if 5 oocytes are cryopreserved and 35.8% (CI 4.3–57.2) if 8 oocytes are cryopreserved [5]. As illustrated by the case of lymphoma, the number of cryopreserved oocytes is generally lower than that in cases of other malignant diseases [6]. In this case, delayed FP performed after chemotherapy treatment and remission could allow oocyte banking to increase the probability of live birth after oocyte thawing [7]. Offering the possibility of delayed FP after fertility-impairing treatment when emergency FP cannot be achieved is sometimes the only option. Starting stimulation before the occurrence of POI becomes a necessity to offer these women a chance to build a family. This systematic delayed FP strategy for women with diminished ovarian reserve (DOR) was implemented in 2015 at the OncoPACA-Corse Cancer platform of the Conception University Hospital in Marseille [8].

To our knowledge, no study has assessed a systematic strategy of delayed FP by oocyte cryopreservation after fertility-impairing treatments. The objective of our study was to investigate the feasibility and efficacy of a center-based strategy for delayed FP after fertility-impairing treatment.

2.1 Study population

We conducted a retrospective cohort study in the fertility preservation unit of a university teaching hospital between January 2015 and December 2020. The study protocol was approved by the ethics committee of the Aix-Marseille University on September 8, 2021 under the number 2021-09-07-03. The research was performed in accordance with relevant regulations, and informed consent was obtained from all participants.

We included all reproductive-age women referred for counseling after fertility-impairing treatment for malign or benign pathologies. Women consulted either for a first delayed FP after fertility-impairing treatment or as an additional cycle when a first emergency FP could be performed before fertility-impairing treatment. The inclusion criteria were as follows: (1) women < 40 years of age with a history of fertility-impairing treatment (ovarian surgery, pelvic radiotherapy, total body irradiation, history of gonadotoxic treatment) and (2) women with DOR (an abnormal ovarian reserve test (i.e. AFC < 5–7 follicles or AMH < 0.5–1.1 ng/ml)) [9]. The noninclusion criteria were as follows: (1) women with permanent amenorrhea and POI (postmenopausal levels of FSH (> 40 IU/L), four or more months of secondary amenorrhea, and age < 40 years) and (2) women who refused to have their medical records used for the investigation [10].

The following three groups of women were compared according to the initial disease that led to fertility impairment:

- Hematological malignancies group: Women who had undergone controlled ovarian stimulation (COS) after chemotherapy or radiotherapy for hematological malignancies (e.g., leukemia, Hodgkin's disease, myeloma).

- Solid tumors group: women who had undergone COS after chemotherapy or radiotherapy for solid tumors (e.g., breast cancer, ovarian cancer, nephroblastoma)

- Benign diseases group: women who had undergone COS after benign gynecological ovarian surgery or gonadotoxic medical therapy for noncancerous pathologies (e.g., endometriosis, ovarian cyst, lupus).

2.2 COS protocol and oocyte vitrification/warming

The COS protocol was prescribed as usual for the three groups.

The dose and type of gonadotropins were determined on an individual basis according to age, body mass index (BMI) and ovarian reserve. All women were monitored with serial transvaginal ultrasounds and hormonal dosages were monitored during stimulation. Ovulation was triggered either by subcutaneous HCG (Ovitrelle, Merck Serono, Germany), by 0.3 mg of triptoreline (Decapeptyl, Ipsen, France) or by both at the same time (dual triggering). The oocytes were retrieved 36 hours later in the operating room and taken to the laboratory where vitrification was performed. One hour after egg collection, the oocytes were denuded, and their maturity was assessed (presence of a polar cell). Only mature oocytes were vitrified. When the number of vitrified oocytes at D0 was < 8 and when there were still immature (GP-) nonvitrifiable oocytes at D0, their culture was continued for another 24 hours. This allowed us to reassess their maturity in view of the possible vitrification of the matured oocytes at D1, even if the recommended timing was not respected in this case. Vitrification Freeze Kit (Vit Kit-Freeze NX, FUJIFILM Irvine Scientific, USA) and vitrification straw (CBS high-security vitrification straws, IMV Technologies, Cryo Bio System, France) were used for the procedure. When thawing, a vitrification thawing kit (Vit Kit-Thaw NX, FUJIFILM Irvine Scientific, USA) was used. The oocytes were thawed mid-morning for microinjection in the early afternoon.

In the subgroup of women who wanted to conceive, metaphase II oocytes were fertilized in vitro according to the standard protocol of our laboratory. For the use of fresh oocytes, ICSI was performed only when sperm abnormalities were present. ICSI was systematically performed for the fertilization of thawed oocytes. Embryo quality was assessed 48 and 72 hours after fertilization, and 1–2 embryos were transferred under ultrasound guidance using a flexible transfer catheter (Cook, Bloomington, U.S.A.). Supernumerary embryos were frozen for subsequent embryo transfer.

2.3 Outcome Measures

The primary endpoint was the number of metaphase II oocytes collected per woman who started COS cycle, whether vitrified or immediately used for IVF. We studied these results per stimulation cycle and per woman.

The secondary endpoints were as follows: (1) the total number of COS cycles performed per woman; (2) the COS cycle cancellation rate for no ovarian response; (3) the oocyte retrieval failure rate; and (4) the CLBR per stimulation cycle with fertilized oocyte, including fresh and frozen embryo transfers.

Standard definitions were used as follows: biochemical pregnancy was defined as positive HCG test 15 days after embryo transfer; clinical pregnancy was defined as the visualization of a positive fetal heartbeat on ultrasound at 7 weeks; and live birth was defined as a live birth after 22 weeks of gestation according to The International Glossary on Infertility and Fertility Care [11].

2.4 Statistical analyses

Quantitative variables were compared using one-way ANOVA with Dunnett’s post-hoc comparison test or the corresponding nonparametric test when appropriate. Categorical variables were analyzed with the chi-square test, Fisher’s exact test or the appropriate test. The statistical analysis was performed using GraphPad Prism software v.8.0.1 (GraphPad Software, La Jolla, CA, USA) with a statistical significance threshold set at 0.05.

During the study period, 8978 women of reproductive age presented to our center for FP or childbearing desire. Among these 8978 women, 445 were referred for delayed FP counseling after fertility-impairing treatment for malign or benign pathologies. Among these 445 women, 69 presented with POI, 17 were too old to benefit from oocyte cryopreservation (> 40 years), 69 had a normal ovarian reserve, 62 preferred to delay COS for oocyte cryopreservation, and 2 refused to have their medical records used for the investigation.

At the same time 76 women did not wish to undergo COS after counseling. Forty-five women did not reply to phone calls and were therefore lost to follow-up after counseling. Six women had already completed their family plans and six other women did not wish to become mothers. Five women had a scheduled COS but never showed up on the day of the first ultrasound examination. Five women did not want to perform COS but they did not give their reason to the practitioner. Four women had a spontaneous pregnancy. Three women had undergone emergency fertility preservation before fertility-impairing treatments and did not wish to undergo additional COS. One woman did not want to perform a COS for religious reasons and another one did not want hormonal treatment.

Finally, a total of 129 women were included in the study. Among these 129 women, 113 started COS for oocyte cryopreservation and/or 25 started COS for oocyte fertilization and fresh embryo transfer because of an immediate pregnancy plan. We studied a total of 244 started COS cycles: 200 COS cycles for FP and 44 COS cycles for IVF-ICSI with fresh embryo transfer. Among these 129 women, metaphase II oocytes were obtained for 111 women and in 19 women, no metaphase II oocytes were obtained (COS cancellation for no ovarian response or oocyte retrieval failure). Three groups of women were composed as previously described: 33 in the hematological malignancy group (including 7 hematopoietic stem cell transplantations), 29 in the solid tumor group, and 67 in the benign disease group. The distribution of diseases that led to gonadotoxic treatments according to the groups is presented in Fig. 1. The baseline characteristics of the 3 groups of women are presented in Table 1. Regarding the initial characteristics of the women, age at initial diagnosis was significantly lower in the hematological malignancy group (20.5 ± 8.0 years) than in the solid tumor group (24.1 ± 9.0 years) and benign disease group (25.4 ± 6.7 years) (p < 0.03). The AMH median levels were 1.4 ± 1.8, 2.5 ± 3.2 and 1.7 ± 1 ng/ml for the hematological malignancy group, solid tumor group and benign disease group, respectively (ng/ml ± interquartile range).

Table 1

Characteristics of women who started controlled ovarian stimulation after fertility-impairing treatment and women’s results of controlled ovarian stimulation after fertility-impairing treatment:
	Hematological malignancies group ( n = 33 )		Solid tumors group ( n = 29 )		Benign diseases group ( n = 67 )		p-value
Age at diagnosis (years)	20.5 ± 8.0		24.1 ± 9.0		25.4 ± 6.7		0.03
Age at first COS (years)	25.9 ± 6.1		28.6 ± 6.7		28.9 ± 5.8		NS
BMI (k/m²)	21.2 ± 3.0		22.2 ± 4.3		23.4 ± 4.4		0.03
Gestity	0.3 ± 0.8		0.2 ± 0.6		0.4 ± 0.8		NS
Parity	0.2 ± 0.5		0.1 ± 0.4		0.1 ± 0.3		NS
Smoking > 10 cigarettes/day	0 (0.0)		1 (3.6)		8 (11.9)		NS
AMH (ng/ml)	1.4 ± 1.8		2.5 ± 3.2		1.7 ± 1.8		NS
FSH (IU/L)	14.1 ± 24.8		9.2 ± 3.9		7.3 ± 2.5		NS
AFC	9.7 ± 8.0		12.5 ± 8.2		10.0 ± 6.7		NS
No history of FP before fertility-impairing treatment	27 (75.0)		26 (92.9)		60 (89.6)		NS
No. of cycle with metaphase II oocyte retrieval		22 (61.1)		25 (89.3)		64 (95.5)		< 0.01
No. of cycle with oocyte retrieval failure		1 (2.8)		1 (3.6)		1 (1.5)		NS
No. of cycle with cancellation for no ovarian response		11 (30.6)		3 (10.7)		2 (3.0)		< 0.01
No. of oocyte vitrification cycle		27 (75.0)		23 (82.1)		63 (94.0)		NS
No. of fresh IVF cycle		5 (13.9)		8 (28.6)		4 (6.0)		0.02
No. of fresh ICSI cycle		1 (2.8)		1 (3.6)		6 (9.0)		NS
No. of oocyte thawing cycle		1 (2.8)		2 (7.1)		3 (4.5)		NS
No. of frozen embryo transfer cycle		2 (5.6)		4 (14.3)		3 (4.5)		NS
No. of COS cycles per woman		1.8 ± 1.0		1.8 ± 1.4		1.8 ± 1.1		NS
Total No. of metaphase II oocyte retrieved per woman		10.7 ± 4.6		12.3 ± 9.1		10.1 ± 7.6		NS
Spontaneous pregnancy		2 (5.6)		0 (0.0)		2 (3.0)		NS
No. of oocytes fertilization cycle		4 (11.1)		5 (17.9)		8 (11.9)		NS
No. of oocytes vitrified return to use cycle		1 (2.8)		1 (3.6)		2 (3.0)		NS
No. of fresh oocytes use cycle		3 (8.3)		6 (21.4)		6 (9.0)		NS
Data are expressed as the mean ± SD or n (%) if not specified. Median are expressed with [1st quartile- 3rd quartile]. COS = controlled ovarian stimulation; BMI = body mass index; AMH = Anti-Müllerian Hormone; FSH = Follicle Stimulating Hormone; AFC = antral follicle count on Day 3; FP = fertility preservation; IVF = in vitro fertilization; ICSI = intracytoplasmic sperm injection; FP = fertility preservation.

Women's results of COS after fertility-impairing treatment are presented in Table 1. The total number of metaphase II oocytes collected per woman who started COS was similar in the hematological malignancy group (mean 10.7 ± 4.6), the solid tumor group (mean 12.3 ± 9.1) and benign disease group (mean 10.1 ± 7.6) (NS).

The total number of started COS cycles performed per woman was similar in the hematological malignancy group (1.8 ± 1.0), the solid tumor group (1.8 ± 1.4) and the benign disease group (1.8 ± 1.1) (NS).

The number of women for whom a COS cycle cancellation for no ovarian response had to be decided was significantly higher in the hematological malignancy group (n = 11; 30.6%) than in the solid tumor group (n = 3; 10.7%) and benign disease group (n = 2; 3%) (p < 0.01).

The number of women who presented an oocyte retrieval failure was similar in the hematological malignancy group (n = 1; 2.8%), the solid tumor group (n = 1; 3.6%) and the benign disease group (n = 1; 1.5%) (NS).

The results of ovarian stimulation per started cycle after fertility-impairing treatment are presented in Table 2. The antagonist protocol was used in 80.4% of the COS cycles (n = 197). The mean number of metaphase II oocytes collected per started COS cycle was similar in the hematological malignancy group (5.5 ± 3.3), the solid tumor group (5.5 ± 4.6) and the benign disease group (5.9 ± 4.4) (NS).

Table 2

Results per started cycle of controlled ovarian stimulation fertility-impairing treatment:
	Hematological malignancies group ( n = 62 )	Solid tumors group ( n = 87)	Benign diseases group ( n = 95 )	p-value
No. of cycles cancellation for no ovarian response	16 (25.8)	6 (6.9)	5 (5.3)	< 0.01
No. of oocyte retrieval failure	2 (3.2)	8 (9.2)	2 (2.1)	NS
Type of stimulation
Oocyte vitrification	54 (87.1)	61 (70.1)	85 (89.5)	< 0.01
IVF	7 (11.3)	20 (23)	4 (4.2)	< 0.01
ICSI	1(1.6)	6 (6.9)	6 (6.3)	NS
Type of stimulation protocol
Antagonist	61 (98.4)	61 (70.1)	75 (78.9)	< 0.01
Random start	1 (1.6)	3 (3.4)	1 (1.0)	NS
Short	0 (0.0)	10 (11.5)	0 (0.0)	0.04
Progesterone block protocol	0 (0.0)	3 (3.4)	7 (7.4)	NS
Long agonist	0 (0.0)	9 (10.3)	10 (10.5)	< 0.01
Daily long agonist	0 (0.0)	0 (0.0)	2 (2.1)	NS
Natural cycle	0 (0.0)	1 (1.1)	0 (0.0)	NS
Length of COS (days)	9.8 ± 1.8	9.9 ± 2.5	10.1 ± 2.5	NS
Total gonadotropin dose (IU)	3444.8 ± 963.4	3250.4 ± 1381.1	3439.1 ± 1207.1	< 0.01
Triggering type
HCG trigger	15 (24.2)	31 (35.6)	27 (28.4)	NS
GnRHa trigger	12 (19.4)	16 (18.4)	14 (14.7)	NS
HCG + GnRHa trigger	18 (29.0)	34 (39.1)	6.8 (3.6)	< 0.01
No. of mature follicles at trigger day	6.6 ± 3.1	6.7 ± 4.6	6.8 ± 3.6	NS
E2 at trigger day (pg/ml)	1182.7 ± 768.7	1868.1 ± 2078.1	1264.8 ± 1127.2	< 0.01
No. of metaphase II oocyte retrieved per COS	5.5 ± 3.3	5.5 ± 4.6	5.9 ± 4.4	NS
Total use of oocytes	5 (3.2)	32 (36.0)	11 (11.6)	NS
No. of oocytes vitrified return to use cycle	1 (1.6)	10 (11.5)	1 (1.1)	NS
No. of fresh oocytes use cycle	4 (6.5)	24 (27.6)	9 (9.5)	< 0.01
Data are expressed as the mean ± SD or n (%) if not specified. Median are expressed with [1st quartile- 3rd quartile]. COS = controlled ovarian stimulation; IVF = in vitro fertilization; ICSI = intracytoplasmic sperm injection; HCG = human chorionic gonadotropin; GnRHa = antagonist gonadotropin releasing hormone; E2 = estradiol

The fertility outcome results after delayed COS post-impaired fertility treatment followed by fertilization are presented in Table 3. The women had an average follow-up of 78.7 ± 75.73 months.

Table 3

Fertility outcome of controlled ovarian stimulation after fertility-impairing treatment in women who planned a pregnancy. Cumulative results per cycle of controlled ovarian stimulation followed by fertilization:
	Hematological malignancies group ( n = 5 )	Solid tumors group ( n = 26 )	Benign diseases group ( n = 10 )	p-value
Age at embryo transfer (years)	36.3 ± 4.6	33.1 ± 2.8	31.7 ± 3.4	NS
Average follow-up after PF (months)	94.3 ± 79.3	82.0 ± 86.4	63.9 ± 61.3	NS
Type of stimulation
Fresh IVF	4 (14.7)	16 (61.5)	4 (40.0)	< 0.01
Fresh ICSI	0 (0.0)	5 (19.2)	5 (50.0)	< 0.01
No. of Cycle of oocyte thawing	1 (20.0)	5 (19.2)	1 (10.0)	NS
Fertilization rate by oocyte	77.6 ± 21.9	66.7 ± 30.7	53.5 ± 41.9	NS
No. of diploid embryos	4.2 ± 1.6	3.0 ± 2.2	2.7 ± 3.2	0.01
No. of cryopreserved embryos	2.2 ± 1.9	0.8 ± 1.9	1.4 ± 2.7	NS
No. of fresh embryos transferred	1.6 ± 0.9	1.2 ± 1.0	0.9 ± 0.9	NS
No. of frozen embryos transferred	0.8 ± 1.3	0.7 ± 1.1	0.5 ± 1.3	NS
Cumulative pregnancy outcomes
Cumulative biochemical pregnancy rate	4 (80.0)	8 (30.8)	4 (80.0)	NS
Cumulative clinical pregnancy rate	1 (20.0)	8 (30.8)	2 (20.0)	NS
Cumulative live birth rate	1 (20.0)	5 (19.2)	2 (20.0)	NS
Data are expressed as the mean ± SD or n (%) if not specified. Median are expressed with [1st quartile- 3rd quartile]. FP = fertility preservation; IVF = in vitro fertilization; ICSI = intracytoplasmic sperm injection.

A total of 202/1222 (16.5%) oocytes were thawed and fertilized. The CLBR per stimulation cycle, including fresh and frozen embryo transfers from thawed or fresh oocytes, was similar in the hematological malignancy group (n = 1; 20%), the solid tumor group (n = 5; 19.2%) and benign disease group (n = 2; 20%) (NS), with a total of 8 live births.

To the best of our knowledge, our study is the first to evaluate a large systematic delayed FP strategy after fertility-impairing treatment for both cancer and benign diseases.

By taking the number of oocytes collected as the main objective, regardless of their subsequent use or the subsequent origin of the disease, we have chosen to place ourselves from the woman's perspective. Comparing all types of women and all types of disease allows us to refocus on the initial goal of fertility preservation and assisted reproductive technology (ART): to give women a real chance of pregnancy.

In our study, no difference was found between the groups concerning the number of metaphase II oocytes retrieved, either per women who started COS cycle or per started COS cycle, irrespective of the initial indication of FP. The number of oocytes retrieved per woman is in agreement with Chan et al., who recovered an overall average of 8 (CI 2–19) metaphase II oocytes per woman after chemotherapy exposure for cancer in 130 women [12]. Legrand et al. reported an average of 6.4 ± 3.4 retrieved oocytes in 70 women with benign ovarian tumors with a history of previous surgery and multiple or large cyst indications [13]. These results are also in agreement with Volodarsky-Perel et al., who found an average of 10 cryopreserved oocytes per woman before gonadotoxic treatments for cancer, regardless of the cancer grade [14]. The fertilization rate after fertility-impairing treatment found in our study is also encouraging and in agreement with that found by Kato et al. [15]. With an overall vitrified-warmed oocyte to live born child efficiency of 6.4%, the mean of 10 cryopreserved oocytes per woman gives these women real opportunities for live birth [16]. In a large study by Cobo et al., when FP was performed before the age of 35 and for malignant disease, the CLBR was 9.1% (-0.7-19) for 5 oocytes, 35.8% (14.3–57.2) for 8 oocytes and 42.9% (19.7–66.1) for 10 oocytes. They concluded that with ~ 25 oocytes, the cumulative probability rises to ~ 95%.

The total of 8 pregnancies achieved in our study led to a 20% live birth rate per stimulation cycle with oocyte fertilization, either vitrified-warmed or fresh.

As the CLBR per oocyte decreases with age, rapid referral after every fertility-impairing treatment should be supported as soon as possible and before the age of 35 years [16]. In a retrospective observational study including 485 women with endometriosis, Cobo et al. reported that the CLBR increased with the number of oocytes per woman, reaching 89.5% (95% CI = 80.0-99.1) for 22 thawed oocytes. In the group aged ≤ 35 years, the CLBR was 95.4% (95% CI = 87.2-103.6) using ~ 20 oocytes compared with that of 79.6% (95% CI = 58.1-101.1) for women aged > 35 years (P < 0.05) [17].

In the long-term after cancer, distress about interrupted childbearing persists, particularly in women without children [18]. Among cancer survivors, the negative impact on quality of life due to reproductive concerns and unmet information needs when making fertility decisions about creating a future family has been reported [19]. Deshpande et al. reported that pretreatment fertility counseling leads to lower levels of posttherapy regret and better quality of life, suggesting that posttreatment counseling may be similarly beneficial [20]. Routinely offering FP counseling to all women after fertility-impairing treatment could improve their overall quality of life, regardless of whether the consultation leads to delayed oocyte cryopreservation.

Offering a systematic delayed FP strategy after chemotherapy and before the occurrence of POI is easy to plan. The arrangement of oncofertility networks and platforms allows for systematic phone calls to women 12 months after their last treatment [21].

An increasing number of authors are focusing their research on FP for nonmalignant diseases [2]. Legrand et al. reported that oocyte banking in women treated for benign ovarian tumors is an efficient strategy, with a mean of 7.0 (± 5.23 SD) cryopreserved oocytes per woman, irrespective of the histological type of tumor [13]. Concerning endometriosis, Cobo et al. reported a mean number of cryopreserved oocytes of 8.5 (± 4.8 SD) per woman for those with a history of unilateral surgery and 8.0 (± 5.7 SD) per woman for those with a history of bilateral surgery. The CLBRs were 40.4% and 49.3%, respectively, with a total of 101 babies born [22]. When focused on age and history of surgery, they observed a CLBR of 52.8% for women under 35 years old and 29.3% for women over 35 years old.

No study has evaluated the benefit of FP on quality of life in women with benign diseases or on the cost-effectiveness balance. Further studies are required to explore these aspects, but given the data on oncofertility, we hypothesize that delayed FP could be beneficial for improving the quality of life of women with decreased ovarian reserve after fertility-impairing treatment.

Some limitations of our study must be discussed. First, the retrospective nature of our study and the low oocyte use rates (16.5%) make it difficult to interpret the results of the CLBR. The large number of women who did not wish to undergo oocyte cryopreservation despite an obvious indication must also be considered. The French insurance coverage for fertility preservation also raises the problem of extrapolation to countries where patients have to pay for their fertility preservation.

The main result of our study is the feasibility of oocyte banking in women with DOR after fertility-impairing treatment with a cumulative number of cryopreserved oocytes between 10.1 (± 7.6 SD) and 12.3 (± 9.1 SD) regardless of the initial disease. The CLBR of 20% per cycle is also important data to provide when counseling referred women.

Regardless of the initial disease that led to DOR after fertility-impairing treatment, oocyte banking should be offered to all reproductive-age women under 35 years of age after every fertility-impairing treatment. The overall improvement in access to FP prior to and after fertility-impairing treatment must be continued through the education of practitioners and throughout the setup of fertility networks [8].

Author contribution: LM wrote the original draft and analysed the data. JL and AH performed the data acquisition. PB, JP and CG conducted the investigations and provided study material resources. PC performed the formal analysis. BC review and edited the draft, did the conceptualization, and directed the project. All authors' revising the draft critically and agree to submission of the final manuscript.

Data aviability statement: Individual participant data are available onhttps://doi.org/10.5281/zenodo.6363664.

Competing Interests: All authors have no conflict of interest.

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No competing interests reported.

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published 20 Sep, 2023

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Feasibility and efficiency of delayed ovarian stimulation and oocyte banking for fertility preservation after fertility-impairing treatment

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Abstract

Purpose

Methods

Results

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1 Introduction

2 Materials And Methods

2.1 Study population

2.2 COS protocol and oocyte vitrification/warming

2.3 Outcome Measures

2.4 Statistical analyses

3 Results

4 Discussion

Declarations

References

Additional Declarations

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Journal Publication

Version 1