Table 2. NICE recommendations modified and included in the SIRU guidelines with specific reason.

1.2.5.1.

2.5.1.

People who are concerned about their fertility should be informed that there is no consistent evidence of an association between consumption of caffeinated beverages (tea, coffee and colas) and fertility problems. However, assumption of more than 2-3 cups of coffee (200-300 mg of caffeine) daily is associated with an increased risk of early pregnancy loss.

Based on Lyngsø et al., 2017 [9]

3.10.1.

1.3.9.1.

People undergoing IVF treatment must undergo testing for HIV, hepatitis B, hepatitis C and syphilis.

Panel decision (unanimity). Based on the recommendations of the Italian Ministry of Health (DLGS 85/2012 e DPR 131/2019).

1.4.2.2.

4.2.2.

Offer surgery for varicocele to improve the chance of natural conception in men with semen abnormalities, clinically remarkable varicocele, and a partner younger than 35 and a good ovarian reserve.

Based on Kim et al., 2013 [10]

1.5.2.2.

5.2.2.

Offer women with WHO Group 2 anovulatory infertility 1 of the following treatments, taking into account potential adverse effects, ease and mode of use, the woman's BMI, and monitoring needed:

• clomifene citrate or

• metformin

Based on Sharpe et al., 2020 [11]

1.5.2.6.

5.2.6.

For women with WHO Group 2 ovulation disorders who are known to be resistant to clomifene citrate, consider one of the following second-line treatments, depending on clinical circumstances and the woman's preference:

• laparoscopic ovarian drilling or

• combined treatment with clomifene citrate and metformin

or

• gonadotrophins

Based on Bordewijk et al., 2020 [12]

1.8.1.3.

8.1.3.

Advise women with unexplained infertility who are having regular unprotected sexual intercourse to try to conceive for a total of 2 years (this can include up to one year before their fertility investigations) before IVF will be considered. Consider a shorter period for women older than 35.

Panel decision (no unanimity). Discrimination of women aged 40-42 was deemed unfair, complicated and in contrast with the national plea for facilitating motherhood to counteract the falling birth rate.

1.8.1.4.

8.1.4.

Offer IVF treatment to women with unexplained infertility who have not conceived after 2 years (this can include up to 1 year before their fertility investigations) of regular unprotected sexual intercourse. Consider a shorter period for women older than 35.

Panel decision (no unanimity). Discrimination of women aged 40-42 was deemed unfair, complicated and in contrast with the national plea for facilitating motherhood to counteract the falling birth rate.

1.9.1.3.

9.1.3.

For people with unexplained infertility, mild endometriosis or mild male factor infertility, who are having regular unprotected sexual intercourse:

• do not routinely offer intrauterine insemination, either with or without ovarian stimulation (exceptional circumstances include, for example, when people have social, cultural or religious objections to IVF)

• advise them to try to conceive for a total of 2 years (this can include up to 1 year before their fertility investigations) before IVF will be considered. Consider a shorter period for women older than 35.

Panel decision (no unanimity). Discrimination of women aged 40-42 was deemed unfair, complicated and in contrast with the national plea for facilitating motherhood to counteract the falling birth rate.

1.11.1.1.

11.1.1.

When considering IVF as a treatment option for people with fertility problems, discuss the risks and benefits of IVF

Panel decision (unanimity). HEFA code of practice is not used in Italy.

1.11.1.3 and 1.11.1.4.

11.1.3.

In women aged < 43 years offer 3 full cycles of IVF, with or without ICSI. If the woman reaches the age of 43 years during treatment, complete the current full cycle but do not offer further full cycles.

In women aged 40 to 42 years IVF, with or without ICSI, provided the following criteria are fulfilled:

• there is no evidence of low ovarian reserve

• there has been a discussion of the additional implications of IVF and pregnancy at this age.

Panel decision (no unanimity). Discrimination of women aged 40-42 was deemed unfair, complicated and in contrast with the national plea for facilitating motherhood to counteract the falling birth rate.

1.12.3.3.

12.5.5.

When using gonadotrophins for ovarian stimulation in IVF treatment: use an individualised starting dose of follicle-stimulating hormone, based on factors that predict success, such as:

- age

- BMI

- presence of polycystic ovaries

- ovarian reserve

Do not use a dosage of follicle-stimulating hormone of more than 300 IU/day

Based on Lensen et al., 2018 [13]

1.12.3.7.

12.3.7.

Do not use growth hormone as adjuvant treatment in IVF protocols.

Based on Liu et al., 2018 [14]

1.12.5.2.

12.5.2.

For the safe practice of administering sedative drugs refer to local Italian Guidelines

Panel decision (unanimity). No specific reference is reported because these guidelines are under development.

1.12.5.3.

12.5.3.

Women should not be offered follicle flushing because this procedure does not increase the numbers of oocytes retrieved or pregnancy rates, and it increases the duration of oocyte retrieval and associated pain.

Based on Georgiou et al., 2018 [15]

1.12.5.5.

12.5.5.

Assisted hatching in fresh embryos is not recommended because it has not been shown to improve pregnancy rates. Evidence for frozen embryos is yet inconclusive.

Based on Zeng et al., 2018 [16]

1.12.6.4.

12.6.4.

Evaluate embryo quality, at both cleavage and blastocyst stages,

according to ESHRE recommendation

Based on ESHRE Special Interest Group, 2017 [44]

1.12.7.3.

12.7.3.

Inform women undergoing IVF treatment that the evidence does not support continuing any form of treatment for luteal phase support beyond 5 weeks' gestation.

Based on Watters et al., 2020 [17]

1.13.1.1.

13.1.1.

The recognised indications for treatment by intracytoplasmic sperm injection (ICSI) include: severe deficits in semen quality, obstructive azoospermia, non-obstructive azoospermia and the use of frozen eggs.

In addition, treatment by ICSI should be considered for couples in whom a previous IVF treatment cycle has resulted in failed or very poor fertilisation.

Panel decision (unanimity). Based on Italian legislation and regulations.

1.15.2.1.

15.2.1.

Oocytes donation programs should adhere to the according to the Italian legislation and regulations (D. Lgs. 16/2010, D. Lgs. 85/2012 and DPR 131/2019).

Panel decision (unanimity). Based on Italian legislation and regulations.

1.16.1.1.

16.1.1.

When considering and using cryopreservation for people before starting chemotherapy or radiotherapy, that is likely to affect their fertility, follow recommendations of the SNLG.

Based on AIOM guidelines. Available at: https://www.iss.it/documents/20126/8403839/LG296_Fertilit%C3%A0_PZ_Oncologici_agg2021.pdf/29e2ba98-a209-8805-cc0b-706f6c7ee2a5?version=1.0&t=1678805156827 (National guideline on fertility preservation available on the website of the Ministry of Health).

1.16.1.7.

16.1.8.

When using cryopreservation to preserve fertility in people diagnosed with cancer, use sperm or oocytes or ovarian cortex.

Panel decision (unanimity). Embryos cannot be stored in a fertility preservation context based on the Italian Legislation (Law n. 40/2004).

1.16.1.12 and 1.16.1.13.

16.1.14

Include in the informed consent the duration of freezing and the modalities to renovate the cryopreservation.

Panel decision (unanimity). Unclear Italian legislation. Risks of litigations if a rigid threshold of duration is given.

1.17.2.3.

17.2.4.

Inform people who are considering IVF treatment that newborns have a modest increase in the risk of malformations. It has not yet been clarified whether the risk is related to the procedure or whether it is related to the condition of infertility.

Based on Liang et al., 2017, Hoorsan et al., 2017, Chen et al., 2018, and Giorgione et al., 2018 [18,19,20,21]