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Ovarian cysts and infertility
1.
OVARIAN CYSTS AND INFERTILITY Prof Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR CONTENTS I. EFFECT OF OVARIAN CYSTS ON FERTILITY II. MANAGEMENT OF OVARIAN CYST IN PREMENOPAUSE III. EFFECT OF OVARIAN CYSTECTOMY ON FERTILITY IV. OVARIAN CYSTECTOMY RECOMMENDATIONS IV ABOUBAKR ELNASHAR
2.
INTRODUCTION ▪ Ovarian cystectomy ▪ a common procedure for the management of benign ovarian cysts in premenopausal women. ▪ usually performed ▪ To prevent cyst complications such as pain, rupture or torsion, or ▪ When there is concern of malignancy, while preserving fertility in those of reproductive age. ABOUBAKR ELNASHAR ▪ The effect of the cyst on fertility 1. Nature 2. Size 3. Number 4. Bilaterality and 5. Risk of recurrence ABOUBAKR ELNASHAR
3.
I. EFFECT OF OVARIAN CYSTS ON FERTILITY ABOUBAKR ELNASHAR 1. FUNCTIONAL OVARIAN CYSTS ▪ Effect on fertility ▪ They almost always regress spontaneously within 1-3 menstrual cycles ▪ Should not require any surgical or hormonal interventions. ▪ With the exception of luteal cysts & persistent functional cysts, functional ovarian cysts are simply by-products of ovulation, so – in theory – they should not have any effect on fertility. ABOUBAKR ELNASHAR
4.
▪ Unilocular ▪ Thin-walled ▪ Anechoic Follicular cyst ABOUBAKR ELNASHAR ▪ The effect on IVF: ▪ Some studies suggest very poor outcome (Biljan et al, 2000) ▪ High cancellation ▪ Decreased follicular recruitment ▪ Low pregnancy rates ▪ Others have failed to report a difference in any outcome (Sampaio et al, 1991) ABOUBAKR ELNASHAR
5.
▪ Treatment 1. Prolonged downregulation with either 1. Progesterone-only pill or 2. Combined contraceptive pill 2. Ultrasound guided aspiration. ABOUBAKR ELNASHAR ▪ Cochrane SR, 2014: ▪ Insufficient evidence to determine whether drainage of functional ovarian cysts prior to COS influences rates of LBR,CPR, number of follicles recruited, or number of oocytes collected ▪ The findings of this review do not provide supportive evidence for drainage, particularly in view of the requirement for anaesthesia, extra cost, psychological stress and risk of surgical complications ABOUBAKR ELNASHAR
6.
Haemorrhagic cysts ABOUBAKR ELNASHAR DERMOID CYSTS ▪ Background: ▪ benign type of germ cell tumour arising from totipotent ovarian cells. ▪ The most common pathological cysts in premenopausal women. ▪ bilateral in 10–20% of cases ▪ grow at a rate of 1.7–1.8 mm per year. ▪ The recurrence rate following cystectomy is 3–4% ABOUBAKR ELNASHAR
7.
3. Haemorrhagic cyst ▪ Result from bleeding into a follicular or corpus luteum cyst. ▪ Like functional cysts, most will resolve spontaneously, but occasionally they can become trapped by pelvic adhesions. ▪ On US and at laparoscopy, persistent haemorrhagic cysts can be mistaken for endometriomas, and diagnosis can only be confirmed by histology. ▪ Like functional cysts, haemorrhagic cysts are unlikely to have any effect on fertility, thus cystectomy for a haemorrhagic cyst is more likely to have an adverse effect. ABOUBAKR ELNASHAR ▪ Effects on ovarian function and fertility 1. Very little or no effect on fertility 2. No significant differences in mean AMH levels between women with dermoid cysts & a control group after adjustment for age and body mass index. The average size of dermoid cysts in that series was 6.3 cm (Kim et al15) 3. IVF outcomes in dermoid cysts with a mean size of 2.4 cm showed no difference in the number of eggs collected. ABOUBAKR ELNASHAR
8.
▪ Why? 1. The follicular density is higher in dermoid cysts than in endometriotic & serous cysts. 2. A clear limit between the dermoid cyst & the ovarian cortex: ovarian cortex is stretched but not damaged by the dermoid cyst (Schubert et al,2005 ) 3. The cortical tissue surrounding dermoid cysts showed normal morphological patterns & a regular vascular network similar to that of the normal ovarian cortex (Maneschi et al, 1993) ABOUBAKR ELNASHAR ▪ Management (Balachandren et al, 2021) ▪ Operating early, while the cyst is still small, may prevent the need for a large cystectomy and thus lower the effect on the ovarian reserve. Why? 1. Dermoid cysts frequently occur bilaterally& have a relatively high recurrence rate 2. Ability to grow to relatively large sizes: repeated surgery, bilateral procedures and relatively large cystectomies; all of which can have an adverse effect on fertility. 3. One study showed a statistically significant reduction in AMH following surgery for cysts over 5 cm in diameter. ABOUBAKR ELNASHAR
9.
Endometriomas Background: ▪ reported in 17–44% of women with endometriosis ▪ are a marker of more severe, deeper disease. ▪ 28% of endometriomas are bilateral. ▪ The risk of recurrence in the same ovary or contralateral ovary following surgery is high, with cumulative rates of 12– 30% after 2–5 years of follow-up. ▪ 81% had recurrence in the treated ovary, ▪ 11% on the contralateral untreated ovary ▪ 8% in both the treated and untreated ovaries (Exacoustos et al, 2006) ABOUBAKR ELNASHAR Endometrioma. Sagittal TVS an ovarian mass with multiple fine internal echoes (arrows) and several hyperechoic mural foci. ABOUBAKR ELNASHAR
10.
1. On Histology (Schubert et al.2005) ▪ Endometriotic cysts had ▪ lower follicular density than dermoid &serous cysts. ▪ Invasion of the surrounding cortex: ▪ Fibrosis ▪ Abnormal morphological patterns and irregular vascular networks. ABOUBAKR ELNASHAR 2 . On ovarian reserve ▪ Lower AMH levels & AFC in women with endometriomas compared with age-matched controls (Chen et al, 2014) ▪ Preoperative AFC for the ovary with the endometrioma was lower than that for the contralateral one, but statistical significance was not reached (Muzii et al, 2014) ABOUBAKR ELNASHAR
11.
3. On ovulation ▪ lower ovulation rates in ovaries containing endometriomas greater than 10 mm in diameter compared with the healthy contralateral ovary (Benaglia et al, 2009 ) ▪ 244 women, with a unilateral endometrioma greater than 20 mm in diameter: No difference in the ovulation rates between the affected ovary and healthy ovary (50.3% vs 49.7%) (Maggiore et al, 2017) ABOUBAKR ELNASHAR 4. On oocyte and embryo quality ▪ Inconclusive ▪ Oocytes retrieved from women affected by endometriosis are more likely to fail in vitro maturation and showed altered morphology and a lower cytoplasmic mitochondrial content than in women with other causes of infertility (Sanchez et al, 27 SR, 2017) ABOUBAKR ELNASHAR
12.
5. On fertility has a detrimental effect. Due to 1. Chronic inflammation affecting quality of oocytes 2. Impaired ovarian function: defective folliculogenesis and fertilisation 3. Poor embryo quality secondary to an altered follicular environment: embryos with reduced implantation capacity 4. Poor ovarian reserve with a significant reduction in the primordial follicle cohort secondary to fibrosis from increased tissue oxidative stress 5. Anatomical distortion and tubal damage or occlusion secondary to pelvic adhesions. ABOUBAKR ELNASHAR 6. On IVF outcome: 1. Lower mean number of eggs retrieved 2. Higher cancellation rates in women with endometriomas compared with no endometriomas (Hamdan et al, 2015) 3. CPR was significantly lower for endometriosis patients 4. LBR were not statistically different, although women with endometriosis had lower CPR (MA, Harb et al, 2013) ▪ Similar LBR and CPR (Hamdan et al, 2015) 5. Higher rates of miscarriage in patients with endometriosis/endometriomas than in healthy controls following spontaneous conception. ABOUBAKR ELNASHAR
13.
Ovarian cystadenomas ▪ Background: ▪ common benign epithelial neoplasms, of which serous and mucinous are two of the most common types seen.36,37 ▪ Serous cystadenomas are more prevalent in menopausal women, while the mucinous type mainly occurs during the third to sixth decade.38 ▪ Mucinous cystadenomas are usually unilateral, but they can grow large in size – on average between 15 and 30 cm ▪ Effect on fertility ▪ Nothing in literature ▪ {relatively large sizes of these cysts}, there is a greater chance of oophorectomy ▪ Surgical spill of mucinous material: pelvic adhesions and subsequent infertility. ABOUBAKR ELNASHAR Ovarian torsion & its effect on fertility ▪ Rare gynaecological emergency ▪ 3% of all emergency gynaecological surgeries ▪ usually involves the ovary & fallopian tube ▪ More commonly seen with benign cysts greater than 5 cm ▪ Effect of torsion: haemorrhage, congestion and apoptosis secondary to ischaemia, which can affect the ovarian reserve ▪ Laparoscopic de torsion: treatment of choice in prepubescent girls and women of reproductive age, regardless of the colour of the ovary at the time of surgery ABOUBAKR ELNASHAR
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TVS: Adnexal torsion. 1. An enlarged ovary (maximal diameter, >5 cm) 2. Congestion: ▪ prominent peripheral nonovulatory follicles ▪ small amount of free fluid (arrow) around the inferior margin. ABOUBAKR ELNASHAR ▪ Effects of Detorsion of the ischaemic ovary ▪ Preserved ovarian function in 91.3% of patients ▪ No difference in the AFC between the affected& contralateral ovary 3 months after detorsion ▪ No difference in the AMH level taken preoperatively on the day of detorsion and at 1 and 3 months postoperatively. ▪ Follicular development and successful fertilisation of oocytes retrieved from the ischaemic ovary following COS ▪ In cases where torsion has occurred in the presence of an ovarian cyst, an elective cystectomy 2–3 weeks later is advised to allow time for the congestion and oedema to resolve ABOUBAKR ELNASHAR
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II. MANAGEMENT OF OVARIAN CYST IN PREMENOPAUSE ABOUBAKR ELNASHAR ▪ RMI = U x M x CA-125 ▪ The ultrasound score is calculated by awarding 1 point for each of the following characteristics: Multilocular cyst Evidence of solid areas Evidence of metastases Presence of ascites Bilateral lesions U = 0, if none of the above listed features is found U = 1, for ultrasound score of 1 U = 3, for ultrasound score ≥ 2 ▪ Menopausal status (M = 1 if premenopausal and M = 3 if postmenopausal) ABOUBAKR ELNASHAR
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NHS Guidelines2020 ABOUBAKR ELNASHAR III. EFFECT OF OVARIAN CYSTECTOMY ON FERTILITY ABOUBAKR ELNASHAR
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1. Effect of ovarian cystectomy on ovarian reserve ▪ There are several ways to perform ovarian cystectomy, but, in principle ▪ Incising the ovarian cortex to identify the cyst capsule ▪ Removing the cyst wall ▪ ±with or without draining ▪ Haemostatic measures. ▪ Factors determine effect of cystectomy on the ovarian reserve. I. Cyst: size, nature, bilaterality and/or recurrent II. Surgery: Method of cystectomy, method of haemostasis III. Surgeon: Skill and experience ABOUBAKR ELNASHAR I. Surgery: 1. Stripping &removing the cyst wall and the thermal damage: coagulation: loss of healthy ovarian tissue: reduction in the follicle density. 2. Laparoscopic excision using the stripping technique: 1. 54% of ovarian tissue is inadvertently excised along with the cyst wall in those with endometriotic cysts 2. 6% in those with non-endometriotic cysts (Muzii et al. 2002) ABOUBAKR ELNASHAR
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II. Cyst: 1. Nature: ▪ 3 months after surgery: recovery of AMH levels to 65% of the preoperative level in both endometriotic and non-endometriotic cysts (Amooee et al, 2015) ▪ Cystectomy for endometriomas: ▪ 30% decrease in AMH ▪ AFC, did not change significantly (Muzii et al.2014 ) {AFC is likely to be less reliable in the presence of endometriomas and that the preoperative AFC underestimates the value: obscure the postoperative reduction in AFC.(Ata et al, 2014} ▪ Reduced ovarian reserve following cystectomy for non-endometriotic cysts, primarily dermoid cysts. ABOUBAKR ELNASHAR 2. The size of the cyst 1. Endometrioma cystectomy: An average loss of 200 µm of ovarian tissue per centimetre increase in endometrioma diameter (Roman et al.2010) ▪ More significant decline in ovarian reserve following removal of endometriomas greater than 5– 7 cm. 2. To surgery when the cyst is small: why? ▪ Especially in those with mucinous cystadenomas, which have a propensity to grow into large cysts ▪ Higher risk of oophorectomy when performing large cystectomies ▪ Significant risk of ovarian torsion with large cyst ABOUBAKR ELNASHAR
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2. Bilateral cystectomy ▪ greater decline in the ovarian reserve than with unilateral surgery ▪ Surgery for bilateral endometriomas: an increased risk of POI ABOUBAKR ELNASHAR 2. Effect of Ovarian cystectomy on IVF outcomes ▪ Cystectomy for endometriomas prior to IVF treatment ▪ Not routinely recommended {not improve IVF outcomes (Benschop et al, SR, 2010) ▪ Cochrane review: no evidence of benefit for CPR.68,69 ▪ Decreased ovarian response to GnT following cystectomy for endometriomas (Demirol et al, 2006) ▪ Surgery should be considered under some clinical circumstances. ABOUBAKR ELNASHAR
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▪ Garcia-Velasco and Somigliana, 2009 ABOUBAKR ELNASHAR 3. Effect of surgical technique on fertility outcomes ▪ Techniques: 1. Excision 2. Drainage & bipolar coagulation or ablation using plasma or laser energy. ▪ Cystectomy is superior to drainage & bipolar coagulation in terms of ▪ Spontaneous PR ▪ Lower risk of recurrence ▪ Pain symptoms among subfertile patients with endometriomas greater than 3 cm ABOUBAKR ELNASHAR
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▪ Laser ablation or plasma energy Vs cystectomy ▪ better preservation of ovarian reserve ▪ recurrence rates at 1 year higher (Carmona et al, 2011) ▪ Laparoscopic suturing was superior to bipolar coagulation when comparing AMH and AFC – even 12 months after surgery (Baracat et al, 2019) ▪ Bipolar vs. haemostatic sealants, the results favoured the use of haemostatic agents. ABOUBAKR ELNASHAR IV. RECOMMENDATIONS FOR OVARIAN CYSTECTOMY ABOUBAKR ELNASHAR
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1. Preoperative Recommendations 1. Ovarian reserve assessments ▪ For women who have not completed their family, in 1. Repeat surgery on the same or contralateral ovary 2. Severe endometriosis and bilateral endometriomas 3. coexistent aetiologies for subfertility, including low sperm parameters in the male partner 4. Advanced reproductive age 5. Coexistent risk factors for POI. ABOUBAKR ELNASHAR ▪ Ovarian cystectomy can reduce ovarian reserve, which can hinder the chance of success with IVF ▪ Significance of Ovarian reserve assessments ▪ An indirect measure of oocyte quantity but are poor predictors of oocyte quality ▪ Should not be used to predict spontaneous conception. ▪ AFC and AMH have been shown to be ▪ Lower in the presence of endometriomas ▪ Not affected by the presence of other types of cysts. ABOUBAKR ELNASHAR
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▪ AFC assessment in endometrioma: ▪ The reduced AFC associated with endometriomas could be associated with an inability to visualise the antral follicles on US in the presence of an endometrioma. ▪ Although the AFC was reduced in the ovaries with an endometrioma, the median number of oocytes retrieved was similar between ovaries with an endometrioma and the contralateral ovaries (Candiani et al, 2018) ABOUBAKR ELNASHAR 2. Discuss fertility preservation options ▪ Indication ▪ ovarian reserve is already compromised ▪ considerable risk of POI ▪ For postpubertal females: egg or embryo storage following ovarian stimulation ▪ The disadvantages of fertility preservation before cystectomy ▪ Delay in surgery ▪ Visceral injury during egg collection, ▪ Pelvic infection from accidental puncture of the cyst ▪ theoretical increase in the risk of torsion of the hyperstimulated ovary. ABOUBAKR ELNASHAR
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3. Pelvic US & a bimanual examination ▪ US: Assess the type, size, number and location (unilateral or bilateral) of the ovarian cysts before surgery ▪ Bimanual examination: identify deep endometriotic nodules in the Pouch of Douglas, which can be difficult to visualise on US. 4. Consent possible risks associated with the surgical procedure, including reduction in ovarian reserve and risk of oophorectomy. 5. Refer the woman to a centre of expertise If the surgery cannot be performed or completed safely, the patient should be referred to a centre of expertise. ABOUBAKR ELNASHAR 6. Blood supply of the ovary 1. Ovarian artery approaches the ovary through the infundibulopelvic ligament 2. An anastomosis between the ovarian artery & ascending branch of the uterine artery/tubal artery, found within the ovarian ligament. These intra-ovarian vessels are found in the anterolateral aspect of the ovary, at the insertion of the mesovarium. ABOUBAKR ELNASHAR
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ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR
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ABOUBAKR ELNASHAR 2. Operative recommendation ▪ Non-endometriotic cysts 1. An incision on the anti-mesenteric surface of ovarian cortex 2. Identify the plane between the cyst wall &the ovarian cortex; develop this plane further 3. Enucleate the cyst or cyst wall (if the contents are spilled or aspirated) by ▪ Combination of blunt & sharp dissection, ▪ Traction & countertraction. 4. Haemostasis by ▪ targeted coagulation of blood vessels or ▪ suturing ▪ Avoid indiscriminate use of diathermy ▪ consider using haemostatic sealants instead of excessive diathermy. 5. Reconstruct ovary ABOUBAKR ELNASHAR
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Ovarian cystectomy. (a) Reveal cleavage plane. (b) Dissect the cyst wall from the ovarian parenchyma. (c,d) Achieve haemostasis by targeted coagulation and/or suturing and then reconstruct the ovary. ABOUBAKR ELNASHAR ▪ Endometriotic cysts World Endometriosis Society (WES) recommends the following approaches: 1. Mobilise the ovary and drain the cyst 2. Incision to reveal the cleavage plane, either 1. On the edge of the cyst opening or 2. Central incision, which divides the cyst into two halves. ▪ Incision should be away from the blood vessels in the hilum/mesovarium. ▪ Use of cold cut at the edge of the cyst opening may assist in identifying the cleavage plane. ABOUBAKR ELNASHAR
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Ovarian cystectomy of an endometrioma. (a)Right ovarian endometrioma and adherent right ovary. (b) Drainage of endometrioma after mobilising the ovary. (c) Exposure of the plan between the cyst wall and ovarian cortex. (d) Vasopressin injection under the cyst capsule. (e)Dissect cyst capsule from the ovarian parenchyma. (f) Cyst capsule after complete removal. (g) Precise spot bipolar diathermy to achieve haemostasis.ABOUBAKR ELNASHAR 3. Saline or diluted synthetic vasopressin may be injected under the cyst capsule ▪ aid dissection& identification of the cyst wall, (0.1–1 unit/ml) ▪ reducing bleeding during cyst removal. 4. Traction and countertraction to dissect the cyst capsule from the ovarian parenchyma ▪ Avoid excessive force to separate a highly adherent cyst from the ovary. This is likely to tear the ovarian tissue: excessive bleeding and the need for coagulation or diathermy, which will further damage normal ovarian tissue. ABOUBAKR ELNASHAR
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5. Haemostasis ▪ Precise spot bipolar coagulation will prevent unnecessary damage to healthy tissue& avoids blind or excessive diathermy ▪ Suturing or intraovarian haemostatic sealant agents ▪ It is important to avoid damaging the major blood supply at the hilum coming in from the ovarian&infundibulopelvic lig 6. Reconstruct the ovary ▪ with monofilament sutures, placed inside the ovary, as the exposed suture may be prone to adhesion formation. ▪ For small cysts: suturing is often not required because the ovarian opening usually approximates spontaneously. ABOUBAKR ELNASHAR Two-step approach for large endometriomas ▪ Opening and draining the endometrioma as described previously, the cyst wall is inspected and a biopsy taken. ▪ GnRHa therapy is then given for 3 months to reduce the thickness of the cyst wall through atrophy and reduction in stromal vascularization ▪ Second laparoscopy in the form of cystectomy, CO2 vaporisation, bipolar diathermy or plasma ablation of the cyst wall lining. ▪ Disadvantages: women have to undergo two invasive procedures ▪ Benefit: ▪ Facilitate the management of larger ovarian endometriomas, ▪ Reduce recurrence rates ▪ Limit the damage to the ovarian reserve.20 ABOUBAKR ELNASHAR
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CONCLUSION ▪ The impact of benign ovarian cysts on fertility depend on nature, size, number, bilaterality & risk of recurrence ▪ Laparoscopic detorsion has the potential to preserve ovarian reserve and should remain the optimal treatment for ovarian torsion in girls and premenopausal women. ▪ Surgery for bilateral endometriomas has been shown to increase the risk of developing POI. ▪ Ovarian reserve assessments before any ovarian surgery in women who have not completed their family. ▪ Considerable pain related to the cyst and who are unsuitable for hormonal therapy will often require surgery. ABOUBAKR ELNASHAR ▪ Before an ovarian cystectomy ▪ age of the patient, the nature of the cyst, rate of growth, risk of recurrence, surgical history and future fertility plans ▪ Assess other causes of subfertility that would increase the likelihood of ART in the future, including male factor ▪ Regardless of whether or not a cystectomy is performed, it is imperative that the risk to fertility and ovarian function is discussed with all patients. ▪ Discussing fertility preservation options when there is a significant risk of injury to a woman’s reproductive potential ABOUBAKR ELNASHAR
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