The landscape of fertility preservation is rapidly evolving. What initially emerged as an urgent intervention prior to gonadotoxic therapies in cancer patients is now expanding to include indications such as endometriosis, ovarian surgery and genetic conditions.
In benign diseases, fertility preservation is rarely an emergency; it is a longitudinal process of counselling and care. It requires a coordinated, multidisciplinary approach so that reproductive considerations are embedded at every stage of diagnosis and treatment. This need for collaboration was the key message from a recent campus in Athens, Greece, organised by SIGs Fertility Preservation and Reproductive Surgery. Early dialogue between surgeons and fertility specialists enables prompt referral for fertility assessment and informs operative planning that minimises reproductive harm.
The opening session set the stage by outlining the fundamental concepts of fertility preservation in benign diseases: how to deliver evidence-based counselling on the probabilities of success, and how the strategy differs from oncological settings.
Claudia Massarotti, from the University of Genova, highlighted that not all oocytes are equal. Human fertility follows an โinverted U-shapedโ curve, influenced not only by the progressive reduction of ovarian reserve but also by the age-related increase in aneuploidy rates.
With advancing age, Professor Massarotti said, more oocytes are needed to achieve a reasonable chance of live birth, and the likelihood of retrieving the necessary number of eggs falls (1). In this context, timeliness becomes everything, she added. Hence, effective fertility preservation requires collaboration across disciplines, early referral for counselling, and long-term care pathways to identify the โsweet spotโ between intervening too soon and waiting until it is too late.
This type of pathway is typical of fertility preservation in benign diseases, when the consultation is not (or shouldnโt be) urgent and more than one cycle is possible in theory.
However, cryopreservation techniques are not the only option to preserve fertility in young women with benign diseases. The campus gave ample discussion space to the minimally invasive surgeonโs role in preserving fertility in patients requiring surgery on the reproductive tract. Professor รzeyir Kalkan, from Koc University in Istanbul, focused on fertility-sparing surgery in adolescents. He emphasised that gynaecological conditions such as dermoid cysts or ovarian torsion require not only conservative surgery over oophorectomy, but also proper surgical technique to minimise the effect on ovarian reserve. Techniques such as careful cyst enucleation and detorsion (in cases of ovarian torsion) should be used to preserve functional ovarian tissue, suturing, rather than surgical energy, should be used for haemostasis to avoid damage in the remaining tissue.
Professor Angelos Daniilidis, from the Aristotle University in Thessaloniki, explored the use of IVF versus reconstructive tubal surgery to manage tubal infertility. This is a controversial topic because IVF is usually the favoured approach. However, he presented surgical techniques such as salpingo-ovariolysis, fimbrioplasty, and neosalpingostomy, which can restore natural conception with pregnancy rates up to 62%, although there is a risk of ectopic pregnancy.ย While IVF offers high success per cycle and is less invasive, reconstructive surgery can be a fertility-preserving option in mild to moderate disease with good ovarian function, providing a chance for natural pregnancies, reduced risks of ovarian hyperstimulation syndrome and multiple gestations. Reconstructive surgery can also result in better patient satisfaction as some might not want to use assisted reproductive technologies (ART).ย
One should not think that the discussion was framed as surgery versus ART. Timely and appropriate surgery may also be good support for ART: for example, special emphasis was given to hydrosalpinx, which negatively affects IVF outcomes due to embryotoxic fluid. Professor Daniilidis presented evidence to show that salpingectomy prior to IVF was shown to improve pregnancy and live birth rates significantly (2).
The second day of the campus started with two sessions dedicated to one of the most common and complex benign diseases that may impact fertility: endometriosis. The first lecture by Professor Michaล Ciebiera, from the Warsaw Institute of Womenโs Health, focused on the importance of early diagnosis as a critical opportunity to protect reproductive potential in women with the condition. Diagnosis can take up to seven years and this delay results, other than in pain and reduced quality of life for women, in disease progression, diminished ovarian reserve, and missed chances for fertility preservation.
Carefully planned endometriosis surgery plays a role too: Professor George Pados, from Aristotle University in Thessaloniki, presented on when and how to operate in endometriosis patients. He emphasised that laparoscopic excision of endometriotic cysts generally offers superior outcomes compared to ablation, with better pain control, and lower recurrence rate. However, cystectomy may reduce ovarian reserve by removing follicles or causing thermal injury. To minimise this risk, Professor Pados said surgical expertise and careful technique are essential.
Newer combined techniques still excise most of the cyst wall but treat areas near the ovarian hilum with ablation with the aim of preserving ovarian volume and function while keeping recurrence low. Ultimately, Professor Isabelle Demesteere, from the Universitรจ Libre de Bruxelles, also explored the role of the progestin medication dienogest, both before and after surgery, to avoid progression and recurrence. Both the surgeon and the reproductive medicine physician agreed that ultimately the decision to operate should depend on symptoms, ovarian reserve, cyst size, and fertility plans, with expectant management or direct IVF being alternatives in selected patients. For deep-infiltrating endometriosis, surgery can relieve pain but its impact on fertility remains uncertain, and shared decision-making is vital.
Professor Michael Grynberg, from the Antoine Beclere University Hospital in France, presented data on cryopreservation procedures for endometriosis patients. As for oocyte vitrification, age and number of oocytes were the principal determinants of success (3). He said the decision of when to freeze is complex: freezing too early is not cost-effective and too late yields poor results. Ovarian tissue cryopreservation may have a role in selected cases, but it is not currently the first option for fertility preservation in these patients.
Other ongoing controversies surrounding ovarian tissue cryopreservation and transplantation were also explored in this campus. Jacques Donnez, from Catholic University of Louvain, a pioneer in this field, investigated the hypothesis of using ovarian tissue both to induce puberty and to delay menopause. Professor Donnez said that the former indication appears less advantageous compared to escalating doses of transdermal oestrogens, given the limited functional lifespan of the graft of maximum 5-6 years. The latter may instead hold potential. Yet this hypothesis is currently made less compelling by the brief duration of graft activity, the surgical requirements, and the easy availability of established hormonal replacement therapies.
Another indication for benign diseases fertility preservation may be genetic pathologies. Marie-Madeline Dolmans, from the Catholic University of Louvain, discussed fertility preservation in patients with Turner syndrome. Oocyte vitrification may be a feasible option in adult women with sufficient ovarian reserve, usually with mosaic Turner syndrome, said Professor Dolmans. Ovarian tissue cryopreservation should be instead performed before the age of 12, ideally before puberty, to maximise success rates as follicles undergo increased apoptosis very early in these patients.
Lastly, Dr Stine Gry Kristensen, from Copenhagen University Hospital, addressed the timing of assisted reproductive technologies (ART) versus expectant management following ovarian tissue transplantation. The senior scientist emphasised that natural conception should remain the first approach beyond clear-cut indications, such as severe male factor infertility, tubal blockage, or heterotopic transplantation. However, the option of ART should be introduced into the discussion if pregnancy has not occurred within six to twelve months. As for the treatment or protocol, Dr Kristensen presented data that shows there is no evidence of one protocol or drug being superior to another. Clinicians must also be prepared for the likelihood of retrieving only a limited number of oocytes from these patients.
The campus ultimately highlighted how fertility preservation in benign conditions requires not only technical expertise but also sustained dialogue between surgeons and reproductive specialists. By combining perspectives, data, and a lively discussion of multiple clinical cases, the meeting promoted an integrated approach that places collaboration at the heart of patient care.
References:
- Doyle JO, Richter KS, Lim J, Stillman RJ, Graham JR, Tucker MJ. Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval. Fertil Steril. 2016 Feb;105(2):459-66.e2. doi: 10.1016/j.fertnstert.2015.10.026. Epub 2015 Nov 18. PMID: 26604065.
- Melo P, Georgiou EX, Johnson N, van Voorst SF, Strandell A, Mol BWJ, Becker C, Granne IE. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD002125. doi: 10.1002/14651858.CD002125.pub4. PMID: 33091963; PMCID: PMC8094448.
- Cobo A, Coello A, de Los Santos MJ, Giles J, Pellicer A, Remohรญ J, Garcรญa-Velasco JA. Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis. Reprod Biomed Online. 2021 Apr;42(4):725-732. doi: 10.1016/j.rbmo.2020.12.013. Epub 2021 Jan 8. PMID: 33573907.
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