Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.

RESEARCH QUESTION: To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed. RESULTS: The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively). CONCLUSIONS: Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies.

Ultrasound findings in infertile women with endometriosis: evidence of concomitant uterine disorders.

Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers (n = 419), with the aim to evaluate the prevalence of concomitant uterine disorders. The US coexistence of endometriosis with uterine fibroids and/or adenomyosis was investigated according to three age intervals (<35years; 35 ≥ years <45; ≥45 years) and to endometriosis phenotypes: ovarian endometriosis (OMA), deep infiltrating endometriosis (DIE), or both. The US diagnosis of fibroids was made in 3.1% of cases, adenomyosis was found in 21.2%, and the co-existence of both uterine disorders with endometriosis was reported in 14.6% of patients. When analyzed according to age, patients aged >35 years were more likely to be affected by uterine fibroids (p = .003), adenomyosis (p = .030) and both adenomyosis and fibroids (p < .0001). No statistically significant association was found between endometriosis phenotypes and myometrial pathologies. Uterine disorders coexistence should be considered in the assessment of women with endometriosis, in order to better define a treatment strategy for infertility, especially in women older than 35 years.

Can cytomegalovirus infection affect male reproductive function? Results of a retrospective single-centre analysis.

Our objective was to investigate whether the chronic cytomegalovirus (CMV) infection can affect semen parameters in men with couple infertility and to assess the impact of male CMV infection on the reproductive outcomes of CMV-seronegative women suffering from tubal factor. Group 1 included CMV IgG-seropositive men, Group 2 CMV IgG-seronegative patients. Seminal parameters, two-pronuclear (2PN) fertilization rate (FR), 1-2-3PN FR, cleavage rate (CR), miscarriage rate (MR), pregnancy rate (PR) and live birth rate (LBR) were collected. Two hundred and twenty-two men were included: 115 (51.8%) in Group 1 and 107 (48.2%) in Group 2. There was reported a low trend towards higher sperm concentration/ml, total sperm count and viability in CMV IgG-seronegative males, compared to CMV IgG-seropositive (p > .05). Semen volume, pH, motility and normal sperm morphology were similar among groups. Considering the subgroup of men, partners of CMV IgG-seronegative females, 65 couples (29.2%) were selected. Median 2PN FR was 67%, total FR 83%, CR 100%, PR/cycle 26.2%, MR 10.8%, LBR/cycle 15.4%. No significant differences were found regarding the reproductive outcomes between CMV IgG-seropositive men and those seronegative. CMV did not seem to play a key role in male reproductive function, as well as in influencing sperm fertility potential in the assisted reproductive outcomes.

'Two countries-two labs': the transnational gamete donation (TGD) programme to support egg donation.

PURPOSE: To evaluate the effectiveness, efficiency, and safety of a transnational gamete donation (TGD) programme based on the shipping of vitrified donor oocytes. METHODS: A retro-prospective observational study was conducted in the Assisted Reproductive Technology Center of the University Hospital of Florence, Italy. The study population included 622 consecutive donor oocyte cycles. A mean number of 6 vitrified oocytes per couple were shipped from two Spanish biobanks. In the receiving centre, gametes were warmed and inseminated and the subsequent embryo transfer (ET) was performed. The main outcome measurement was LBR. Secondary outcomes included oocyte survival rate, ICSI damage rate, normal fertilization, cleavage, and implantation rate (IR) in both 'fresh' and cryotransfer cycles. RESULTS: A total number of 3536 mature oocytes were warmed with 81.4% surviving oocytes. 2PN oocytes were 1941 with an ICSI normal fertilization rate of 70.4% and a cleavage rate of 93.4%; 857 day-3 embryos were transferred in 498 women, 63 blastocysts in 44. Couples with at least one vitrified embryo were 181 (32.3%). IR was 25.1% and 33.1% for day-3 ET and blastocyst stage respectively. Crude pregnancy rate and LBR after the first ET were 35.5% and 27% correspondingly with a conservative cumulative LBR of 34% and an optimal LBR of 51.4%. CONCLUSION: Imported vitrified donor oocytes retain their competence and are capable of resulting in ongoing pregnancies and healthy babies in a proportion comparable to other existing systems as egg donation with vitrification/warming in the same laboratory and transnational fresh oocyte donation.

Severe recurrent endometriomas in a young woman with congenital von Willebrand disease.

The pathophysiology of severe endometriosis in young women remains unknown. Menorrhagia, or heavy and prolonged menstrual bleeding, is the most common symptom experienced by women with von Willebrand disease (vWD) and represents a possible risk factor for developing endometriosis. A 17-year-old woman affected by vWD presented with severe dysmenorrhea and heavy menstrual bleeding. After being diagnosed with multiple ovarian endometriomas, the patient underwent repeated surgeries due to suspicious appearance of recurrent pelvic masses. vWD may be a risk factor for developing severe endometriosis, and patients with endometriosis should be screened for vWD and other bleeding disorders. Ovarian endometriomas in such patients might present a more severe progression and unique ultrasound findings, mimicking malignancies.

The effect of low-dose ovarian stimulation with HMG plus progesterone on pregnancy outcome in women with history of recurrent pregnancy loss and secondary infertility: a retrospective cohort study.

We assessed the outcome of pregnancy in women with a history of recurrent pregnancy loss (RPL) following treatment with low-dose human menopausal gonadotropin (HMG)+progesterone or progesterone alone. This single-center retrospective cohort study included data from women diagnosed with RPL and treated between February 2005 and December 2012 with one cycle of HMG + progesterone or progesterone alone. Primary endpoint was the rate of ongoing pregnancies and losses by treatment, age (<38 vs. ≥38 years) and in the subgroup with unexplained RPL. Of 169 RPL patients, 35.5% (n = 60) received HMG + progesterone and 64.5% (n = 109) progesterone alone. Compared to progesterone alone, HMG + progesterone led to a lower, although not significant, frequency of losses (3.3% vs. 11.9%, p = .09) and a twofold higher rate of ongoing pregnancies (41.7% vs. 19.3%, p = .002). Similar results were obtained in the subgroup of patients with unexplained RPL (ongoing pregnancies: 48.1% upon HMG + progesterone vs. 21.3% upon progesterone, p = .03; losses: 0% vs. 8.5%, respectively, p = .29) and in those <38 years (ongoing pregnancies: 47.4% vs. 18.8%, respectively, p = .003; losses: 5.3% vs. 10.9% respectively, p = .47). These findings suggest that HMG in women with RPL may reduce the rate of miscarriages and increase that of live births regardless of RPL cause and in women aged <38 years.

A Biochemical Approach to Detect Oxidative Stress in Infertile Women Undergoing Assisted Reproductive Technology Procedures.

Oxidative stress plays a major role in critical biological processes in human reproduction. However, a reliable and biologically accurate indicator of this condition does not yet exist. On these bases, the aim of this study was to assess and compare the blood and follicular fluid (FF) redox status of 45 infertile subjects (and 45 age-matched controls) undergoing in vitro fertilization (IVF), and explore possible relationships between the assessed redox parameters and IVF outcomes. Reactive Oxygen Species (ROS) production, assessed by flow cytometry analysis in blood leukocytes and granulosa cells, significantly increased (p < 0.05) in infertile patients. Also, oxidative stress markers-ThioBarbituric Acid-Reactive Substances (TBARS) as an index of lipid peroxidation, and Oxygen Radical Absorbance Capacity (ORAC) to account for total antioxidant capacity, both assayed by fluorometric procedures-in blood and FF were significantly (p < 0.001) modified in infertile patients compared to the control group. Moreover, a significant correlation between blood redox markers and FF redox markers was evident. An ORAC/TBARS ratio, defined as the redox index (RI), was obtained in the plasma and FF of the patients and controls. In the patients, the plasma RI was about 3.4-fold (p < 0.0001) lower than the control, and the FF RI was about six-fold (p < 0.0001) lower than the control. Interestingly, both the plasma RI and FF RI results were significantly correlated (p < 0.05) to the considered outcome parameters (metaphase II, fertilization rate, and ongoing pregnancies). Given the reported findings, a strict monitoring of redox parameters in assisted reproductive techniques and infertility management is recommended.

Three-Dimensional Power Doppler Vascularization in Women With Ovarian Endometriomas and Relationship With Associated Painful Symptoms.

OBJECTIVES: The objective of the study was to evaluate the correlation between endometrioma-associated pain and lesion vascularization as measured with 3-dimensional power Doppler transvaginal sonography. METHODS: Endometriomas were examined, and 4 indices were obtained: mean grayness, flow index, vascularization index, and vascularization-flow index. Dysmenorrhea, chronic pelvic pain, and dyspareunia were analyzed in terms of severity, presence/absence, and duration. RESULTS: Twenty-nine women were selected. The univariable association of painful symptoms in terms of presence/absence and duration was low with the exception of mean grayness with the presence of chronic pelvic pain (ß = -0.106; P = .047; 95% confidence interval, 0.810 to 0.998). The R2 value increased to 0.226 for dysmenorrhea (ß = -0.475; P = .029) when analyzing the association between the vascularization index and the severity of painful symptoms. The visual analog scale scores for chronic pelvic pain and dyspareunia were higher (R2 = 0.300; ß = -0.547 and -0.548, respectively; P = .028 and .053). CONCLUSIONS: We observed an inverse association between the severity of pain and endometrioma vascularization. Further larger studies are required to confirm our findings.

Ultrasound-guided excision of rectus abdominis muscle endometriosis.

We report a rare case of rectus abdominis muscle endometriosis excised under ultrasound guidance. A 36-year-old woman came to our observation presenting an abdominal nodule located in the right side of the umbilical area. Ultrasound of the abdominal wall showed two hypoechogenic nodules in the context of the right rectus abdominis muscle and a fine-needle aspiration, performed under ultrasound guidance, confirmed the diagnosis of endometriosis. The patient underwent surgical excision of the lesions. Intraoperative localization was performed through ultrasonography. In our case, the diagnosis was essentially based on ultrasound scan. Computed tomography and magnetic resonance imaging were not performed. A high-resolution ultrasound is a simple, inexpensive and safe method and is sufficient for indicating surgery. Furthermore, the use of intraoperative ultrasound allowed adequate margins of excision.

Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?

This study investigated the relationships between ovarian endometrioma size, ovarian responsiveness and the number of retrieved oocytes following ovarian stimulation. A prospective study was conducted in a public clinical assisted reproduction centre. A total of 64 infertile women with monolateral endometriomas undergoing IVF or intracytoplasmic sperm injection were included in the study. The total number of follicles, number of follicles ≥ 16 mm and number of oocytes retrieved of ovaries containing endometrioma and normal ovaries were compared. Multivariate linear regression was used to assess whether number of follicles and collected oocytes varied by endometrioma size, age, basal FSH concentration. Significantly lower numbers of follicles ≥ 16 mm (P = 0.024) and oocytes retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In patients with endometriomas ≥ 30 mm, endometrioma size was the most influential contributor to the total number of follicles and oocytes retrieved. Ovarian endometriomas result in reduced response to ovarian stimulation, compared with the response of the contralateral normal ovary in the same individual. In case of endometriomas <30 mm, basal FSH concentration remains the most important prognostic factor for oocyte retrieval.

Adnexal masses: what is the role of ultrasonographic imaging?

PURPOSE: Adnexal masses represent a common finding among both premenopausal and postmenopausal women. This article will concentrate on the importance of an accurate preoperative diagnosis of adnexal masses that may be encountered in the course of an assessment of the female pelvis. The ultrasonographic modalities including two-dimensional, Doppler, three-dimensional and real-time four-dimensional approach, the accuracy of the technique, and the role of second-level exam will be discussed. METHODS: In this review, we searched for the most relevant articles on the topic with a special focus on the importance of an accurate preoperative diagnosis of adnexal masses, the different ultrasonographic modalities, and the role of second-level exam. RESULTS: The primary goal of diagnostic evaluation is to exclude malignancy. Furthermore, differentiation among pelvic masses with non-malignant features is relevant as well since suitable counseling and treatment depend on the suspected histology. Ultrasound represents the first-line modality for assessing adnexal masses and showed a very accurate examination. Ultrasound, performed by experienced operators, is effective in the morphologic evaluation of the adnexal masses and is useful in discriminating between benign and malignant lesions. Second-level exams may include assessment by an experienced ultrasound examiner, magnetic resonance imaging, and computed tomography. CONCLUSION: Ultrasound represents the first-line modality for assessing adnexal masses. Predicting the nature of an adnexal mass is essential regarding counseling, clinical management and surgical planning in such patients. Pattern recognition can accurately diagnose the majority of the benign masses and malignancies.

Enhanced production of bioactive isoprenoid compounds from cell suspension cultures of Artemisia annua L. using ß-cyclodextrins.

Plant cell cultures as valuable tools for the production of specific metabolites can be greatly improved by the application of elicitors including cyclodextrins (CDs) for enhancing the yields of the desired plant compounds. Here the effects of 2,6-dimethyl-ß-cyclodextrins (DIMEB) on the production of carotenoids and quinones from Artemisia annua L. cell suspension cultures were investigated. The addition of 50 mM DIMEB induced an early increase of intracellular carotenoid and quinone contents, which could be observed to a higher extent for lutein (10-fold), Q9 (3-fold) and Q10 (2.5-fold). Real Time PCR analysis revealed that the expression of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) gene in DIMEB treated cell cultures after three days was 2.5-fold higher than in untreated samples, thus suggesting that the DIMEB induced increase of carotenoids and quinones could be due to the induction of the plastidial isoprenoid biosynthetic route. In addition, the DIMEB treatment induced an enhanced release of carotenoids and quinones into the culture medium of A. annua cell suspension cultures possibly due to the ability of CDs to form inclusion complexes with hydrophobic molecules.

Endometriosis and Infertility: A Long-Life Approach to Preserve Reproductive Integrity.

Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was indicated as second-line treatment or in the case of male factor. The combined approach of surgery followed by ART proved to offer higher chances of pregnancy in infertile women with endometriosis. However, it was highlighted how pelvic surgery for endometriosis, especially in cases of ovarian endometriomas, could cause iatrogenic damage due to ovarian reserve loss, adhesion formation (scarring), and ischemic damage. Furthermore, in the last few years, the trend to delay the first childbirth, recent technological advances in ultrasound diagnosis, and technological progress in clinical and laboratory aspects of ART have certainly influenced the approach to infertility and endometriosis with, ART assuming a more relevant role. Management of endometriosis should take into account that the disease is chronic and involves the reproductive system. Consequently, treatment and counselling should aim to preserve the chances of pregnancy for the patient, even if it is not associated with infertility. This review will analyse the evolution of the management of infertility associated with endometriosis and propose an algorithm for treatment decision-making based on the most recent acquisitions.

Ovarian surgery for bilateral endometriomas influences age at menopause.

BACKGROUND: Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure. METHODS: In a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated. RESULTS: From over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002). CONCLUSIONS: Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.

Impact of endometriosis on in vitro fertilization and embryo transfer cycles in young women: a stage-dependent interference.

OBJECTIVE: Endometriosis is a frequent indication for in vitro fertilization and embryo transfer (IVF-ET). Its influence on IVF-ET cycles remains controversial. We evaluated the impact of the severity of endometriosis on IVF-ET cycles in young women. DESIGN: Retrospective cohort study. SETTING: Academic tertiary referral centre. SAMPLE AND METHODS: In a retrospective cohort analysis, 164 IVF-ET cycles in 148 women with endometriosis-associated infertility were analyzed. Eighty cycles performed during the same period on 72 consecutive women with tubal infertility were considered as controls. All patients were younger than 35 years old. MAIN OUTCOME MEASURES: Response to controlled ovarian hyperstimulation (COH), number of oocytes retrieved, fertilization, implantation and pregnancy rate (PR). RESULTS: Clinical PR was lower in the group with endometriosis (all stages) in comparison with the tubal factor group. Higher total gonadotropin requirements, lower response to COH and lower oocyte yield were also found in the endometriosis group. Stage-stratified analysis showed a lower fertilization rate in stage I-II (52.6% stage I-II, 70.5% stage III-IV and 71.9% tubal factor). In stage III-IV endometriosis there was a higher cycle cancellation rate, a reduced response to COH and a lower PR compared with both the stage I-II and the tubal infertility groups (PR 9.7, 25 and 26.1%, respectively). CONCLUSIONS: Stage III-IV was strongly associated with poor IVF outcome. A decreased fertilization rate in stage I-II might be a cause of subfertility in these women, owing to a hostile environment caused by the disease.

Impact of cardiovascular burden on coagulation pathway in apparently healthy women planning oocyte donation.

BACKGROUND: Hormonal fertility treatments are associated with increased coagulation factors inducing procoagulant milieu and possibly thrombotic risk. OBJECTIVE: To assess coagulation by ROTEM and coagulation tests in apparently healthy infertile women before oocyte donation procedure. METHODS: We enrolled 51 women (Assisted Reproductive Technology Centre, Florence). ROTEM and coagulation parameters were assessed before the start of infertility treatment. RESULTS: We divided women in 3 groups according to the number of cardiovascular risk factors: Group A (n = 10), Group B (n = 16), and Group C (n = 25). By considering ROTEM Extem test, a significantly increased of MCF, TPI, and G were observed in groups B (p = 0.005, p = 0.03, and p = 0.007) and C (p = 0.01, p = 0.05, and p = 0.005) in comparison to group A. As regards ROTEM Intem test, the TPI and G values were significantly higher in groups B and C in comparison to group A (p < 0.01). MCF by Fibtem test significantly increased in groups B and C than in group A (p = 0.004 and p = 0.002, respectively). FVIII, vWF:Ag and D-dimer values significantly increase according to the presence of≥2 risk factors. CONCLUSIONS: Data from coagulative assessment permit to sensitively identify women with potentially procoagulable state, which represents a risk factor of thromboembolic event during hormone treatment.

The effects of COVID-19 lockdown on lifestyle and emotional state in women undergoing assisted reproductive technology: Results of an Italian survey.

PURPOSE: On March 8, 2020, the Italian Government implemented extraordinary measures to limit viral transmission of COV-19/SARS-CoV-2. We evaluated the impact of COVID-19 lockdown on lifestyle and emotional state in women planning infertility treatments. BASIC PROCEDURES: We performed a quantitative research study using a web-based survey, in 140 women referred to Assisted Reproductive Technologies Center. MAIN FINDINGS: We observed changes in body weight during lockdown in 80 % of women, and a significant increase in BMI in comparison to that observed before (p=.001). We observed a high percentage of non-adherence to the Mediterranean pattern during lockdown due to higher frequency of consumption of sweet/pastries, cheese and meat, rather than fruit, vegetables and legumes. Before lockdown 36.4 % women were snack consumers while during lockdown 55 % (p=.002). By considering individuals' attitude to snack consumption, we observed an increase related to boredom (p=<.0001) and anxiety (p=.05) during lockdown. Increased levels of anxiety and sadness were observed in about 30 %, and of boredom in 25 %. The percentage of women worried about their planning infertility treatment was more than 50 %. PRINCIPAL CONCLUSIONS: Quarantine-related restrictions strongly influenced lifestyle psychological behavior leading to an increased burden of cardiovascular disease.

Cardiometabolic and Thrombotic Risk Profile in Women Undergoing Oocyte Donation for Assisted Reproduction.

Background: The last two decades have seen a growing number of pregnancies in women who needed the donation of oocytes. With oocyte donation pregnancies, studies on obstetric outcomes among these women revealed an increased incidence of pre-eclampsia and pregnancy-induced hypertension. Furthermore, several studies have found a higher incidence of low birth weight, preterm birth, and delivery by cesarean section in oocyte donation rather than in women subjected to assisted reproduction techniques (ART) with autologous oocytes. Numerous studies have also shown a deep connection between cardiovascular and thrombotic risk factors and adverse pregnancy outcomes. In this setting, to strictly assess the preconceptional risk for women who undergo egg donation to achieve pregnancy, the aim of our study is to draw a detailed assessment of the vascular risk profile of patients with gamete donation ART indications through the evaluation of comorbidities and cardiometabolic and thrombophilic markers Materials and Methods: Patients undergoing ART with oocyte or sperm donation or double donation of gametes underwent a careful clinical assessment through a detailed personal and family anamnesis and they were evaluated for cardiometabolic and thrombophilic profile. Clinical and demographic characteristics, comorbidities, and biohumoral parameters were collected. The study was approved by the Regional Ethical Committee(Em 2018-017 CINECA 10189). Results: We evaluated 525 women. Around 73.1% were >40 years and 35% of them were older than 45 years. There was a high prevalence of dyslipidemias (58.1%), smoking habit (24.6%), a body mass index >25 in 28.6% of patients, a high abdominal circumference in 58.1% of cases, a prevalence of acquired thrombophilia in about 7% and hereditary of 19.2%. Around 39.2% of patients had total cholesterol >200 mg/dL, 19.5% had high-density lipoprotein <48 mg/dL and 43.6% had low-density lipoprotein >115 mg/dL, and 6.9% had triglyceride values >150 mg/dL. Conclusions: A careful assessment of the preconceptional status of patients undergoing ART programs with oocyte donation can be highly recommended.