[Infertility over forty: Pros and cons of IVF]. / Prendre en charge les femmes de 40ans et plus en FIV : pour ou contre ou pour et contre ?

The population attempting pregnancy and having babies is ageing. The declining fertility potential and the late age of motherhood are increasing significantly the number of patients over forty consulting infertility specialists. Assisted reproductive technologies (ART) cannot compensate the natural decline in fertility with age. In France, in public hospital, ART is free of charge for women until 43 years, over 43, social insurance does not reimburse ART. Hence, 43 years is the usual limit, but between 40 and 42 is ART useful? The answer varies according to physicians, couples or society. On medical level, the etiology of the infertility must be taken into account. If there is an explanation to infertility (male or tubal infertility) ART is better than abstention. If the infertility is only due to age the question is raised. In France, the reimbursement by the society of a technique with very low results is discussed. However efficacy is not absolutely compulsory in Medicine. On the opposite to give false hopes may be discussed too. To obtain a reasonable consensus is rather difficult.

[Social egg freezing: which problems?]. / Conservation ovocytaire, quelle problématique ?

In today's society, many women push pregnancy further away from the "right" childbearing age. Assisted reproduction, except egg donation, is unable to fully overcome the effect of age on fertility loss. The effectiveness of oocyte vitrification is demonstrated, and oocyte vitrification is allowed in the French Bioethics law of 2011. In the French law, oocyte' s cryopreservation is proposed to oocyte donors without child. Social egg freezing for non-medical reason is already legal in some countries, but leads to new debates and discussions.

[Is it possible to avoid working on weekends in an Assisted Reproductive Technology program?]. / Peut-on éviter le travail du week-end en Assistance Médicale à la Procréation ?

Is it possible to safely avoid weekend oocyte retrievals and embryo transfers? It is possible to safely avoid Sunday oocyte retrieval and embryo transfers during GnRH agonist or antagonist cycles, to avoid oocyte retrievals 2 days seem also possible by delaying or advancing hCG administration in both analogs cycles but it is more difficult to avoid embryo transfers during two days. In intra uterine insemination programs, it is possible to avoid ovulation monitoring and inseminations by the use of GnRH antagonists. In IVF programs, ovulation monitoring could be avoid on weekends but the risk of ovarian hyperstimulation would exists in case of polycystic ovary or polycystic like ovary.

[Endometrial preparation in oocyte recipients]. / Préparation endométriale chez les receveuses dans un programme de don d'ovocytes.

Oocyte donation is offered to patients with premature ovarian failure to achieve pregnancy when no other assisted reproductive technology is possible. Some clinical and biological factors have been identified for influencing the outcome of oocyte donation cycles. Embryo implantation depends on embryo quality, method for the embryo transfer, and endometrial differentiation. In our center, the oocyte recipients receive for the endometrial preparatory cycle the same treatment that for the patients undergoing frozen embryos transfers, with good clinical pregnancy rates, about 35% per transfer. Estrogen and progesterone supplementation with GnRH agonist down regulation are used in synchronized protocols or for frozen embryos transfers. The synchronization between recipient's endometrium and donor's ovarian stimulation is very restrictive. Nowadays, the oocytes vitrification lithens the oocyte donation process: the endometrial preparation has a limited duration and is well controlled, and embryos that are transferred are all fresh embryos.

[Low circulating anti-Müllerian hormone and normal follicle stimulating hormone levels: which prognosis in an IVF program?]. / Pronostic en fécondation in vitro des patientes ayant une AMH basse et une FSH normale.

OBJECTIVE: To evaluate the results of controlled ovarian hyperstimulation (COH) for IVF in patients with low anti-Müllerian hormone (AMH) and normal basal follicle stimulating hormone (FSH) and Estradiol levels (≤50 pg/mL). PATIENTS AND METHODS: A retrospective cohort study including 704 patients for whom AMH and FSH levels (measured between days 3 and 5 of the menstrual cycle) were available, is performed in the IVF center at the Sèvres Hospital (France). Three groups are designed and analyzed: group 1 with AMH less or equal to 2 ng/mL and FSH less or equal to 10 mUI/mL (study group), Group 2 with AMH greater than 2 ng/mL and FSH less or equal to 10 mUI/mL (control group) and Group 3 with AMH less or equal to 2 ng/mL and FSH greater than 10 mUI/mL (group with decreased ovarian reserve). RESULTS: IVF outcome for patients from the study group is significantly worse than that of the second but not than that of the third group. In the first group, the number of retrieved oocytes, the number of total obtained embryos, the clinical pregnancy rate and the live birth rate are significantly lower than in the second group; moreover, there are more cancelled cycles because of poor response in the first group. There is no difference with the third group. DISCUSSION AND CONCLUSIONS: This study shows that women with a low baseline AMH have a similar response to COH to the poor responders patients with a decreased ovarian reserve revealed by an elevated FSH level. Thus, when a woman undergoing IVF cycle presents a low AMH, she might be considered as a poor responder patient regardless of the FSH level and, although the clinical pregnancy rate is not so disappointing (18%), the couple should be informed of a higher risk of cycle cancellation.

[The place of ovarian drilling in the management of polycystic ovarian syndrome (PCOS)]. / Place actuelle du drilling ovarien dans la prise en charge du syndrome des ovaires polykystiques (SOPK).

The surgical approach has been a long-lasting option for ovulation restoration in patients presenting with polycystic ovarian syndrome. It consists of ovarian drilling with monopolar, bipolar energy or laser through laparoscopic or vaginal hydrolaparoscopic route. It is intended to be used as a second line therapy as an alternative to gonadotropins in patients with resistance or failure after clomiphene citrate. The results in terms of ovulation restoration and live births make it an attractive alternative with less complications such as multiple pregnancies and ovarian hyperstimulation syndrome.

[In Vitro Fertilization: beware of oocyte retrieval without oocyte!]. / Fécondation in vitro : ponction blanche : méfions-nous !

A 30-year-old woman undergoing an In Vitro Fertilization (IVF) treatment for tubal infertility and for whom no oocyte was retrieved at the puncture ("white puncture") presented an ectopic pregnancy. The patient was asymptomatic except some bleeding events reported for several days prior to the puncture. The ovulation monitoring was normal throughout the stimulation by gonadotrophin and hCG was administered for the final oocyte maturation on the twelfth day of stimulation at a rate of 2771 pg/ml of estradiol with a perfect ultrasound follicular growth. This case demonstrates that we have to beware of a "white puncture" and that the hCG measurement the day of the oocyte retrieval is necessary because of the possibility of an ectopic pregnancy.

[Single embryo transfer: is Scandinavian model valuable in France?]. / Faut-il systématiser le transfert de l'embryon unique ? Le modèle scandinave est-il applicable en France ?

The aim of infertility treatment is clearly to obtain one healthy baby. If the transfer of a top quality single embryo could provide a baby to all the patients, there would be no more discussion. The problem is that, nowadays, French pregnancy rates after fresh embryo or frozen embryo transfer are not the same as in Nordic countries. All studies show that in unselected patients, single embryo transfer decreases twin pregnancy rate but decreases pregnancy rate too. Pregnancy rate is dependent on embryo quality, women's age, rank of IVF attempt (clear data) but also on body mass index, ovarian reserve, smoking habits. All these data cannot be taken into account in a law. That is the reason why a flexible policy of transfer adapted to each couple is preferable. Each couple and each IVF team are unique and must keep the freedom to choose how many embryos must be transferred to obtain healthy babies, and to avoid twin pregnancies but without demonizing them.

[Premature ovarian failure: which approaches?]. / L'insuffisance ovarienne prématurée: quelles alternatives?

Premature ovarian failure (POF) occurs in one case of 10,000 in women below the age of 20, one case of 1000 below 30 and 1% in women before the age of 40. In 80% of POF cases, the etiology is unknown, except for Turner syndrome. Spontaneous fertility is very weak, only 3 to 10% of the patients will have natural conception. If the diagnosis is confirmed, ovarian stimulation usually fails. When fertility is desired, the alternative treatments are oocyte and/or embryo donation or adoption and "learn to be happy just in couple". Psychological management is always necessary.

[A study comparing previous induced abortion rates in populations of newly delivered women and infertile women]. / Etude comparative sur les antécédents d'interruption volontaire de grossesse dans une population de femmes infertiles et dans une population de femmes accouchées.

OBJECTIVE: For years, induced abortions (IA) have been deemed responsible for altered fertility. The implication of various mechanisms including tubal infertility, intra-uterine adhesions, spontaneous abortion, ectopic pregnancy, cervical incompetence, shortened gestations, and any psychological trouble leading to anovulation has been raised. Though many authors find no evidence of an increased risk on fertility for women, whose IA is not complicated by infection, it might sometimes be insinuated that infertility is the consequence of previous abortion. Thus, we compared the rate of patients with any prior IA in a population of newly delivered women and in women ongoing IVF. PATIENTS AND METHODS: A retrospective study was conducted at Sèvres hospital, comparing two populations of women, newly delivered women (n=1738) between January 1st and December 31st 2005, and women ongoing IVF at the same period (n=430). We reported the number of previous medical or surgical induced abortions and compared it in both groups. Another analysis compared these rates, among two subgroups of women with one or more prior pregnancy (secondary infertility (n=148), and secondary gestation (n=1088). RESULTS: The rate of prior IA was not different in the two populations. In the IVF group, 13% (n=56) had undergone one or more IA, versus 16.7% (n=291) in the newly delivered group (P=0.06). Among women with previous pregnancy, 37.8% (56) women of the IVF group had undergone one or more previous IA, versus 26.7% (291) of the newly delivered women (P=0.007). DISCUSSION AND CONCLUSION: As expected by literature data on IA and fertility, rates of prior induced abortions were not different in the population of fertile women versus infertile. However, women with one or more previous pregnancy are more likely to have undergone previous IA in the IVF group than in the newly delivered group, possibly due to a bias of age. More data are requested to eliminate linkage between IA and infertility.

[Intra-uterine insemination: ovarian stimulation or not?]. / Insémination intra-utérine: pourquoi continuer à stimuler l'ovulation?

Conflicting results have been published about intra-uterine insemination efficacy. In many studies, success rates is due to ovarian stimulation and number of follicles. In the present fight against multiple pregnancies, ovarian stimulation is discussed and present pregnancy rates are weak. Our aim is to demonstrate that there is a place for the association controlled ovarian hyperstimulation and intra-uterine insemination in the field of infertility treatments. It is possible to try and recognise women at high risk of multiple pregnancies, keeping the benefit of ovarian stimulation.

[Is tubal and uterine surgery deleterious to ovarian reserve?]. / La chirurgie tubaire et utérine a-t-elle un effet délétère sur la fonction ovarienne?

Changes in menstrual pattern after tubal sterilisation have been reported for more than 50 years. Hence all tubal surgeries have been suspected of altering the ovarian reserve, by damage to the ovarian blood vessels. Recent studies showed that tubal surgery has no significant adverse effect on doppler flow indice and hormonal markers. Hysterectomy and uterine artery embolization seem to decrease ovarian reserve in perimenopausal women. Uterine artery embolization does not seem to have adverse effects on normally functioning ovaries.

[Obstetrical prognosis improvement in patients exposed in utero to diethylstilbestrol with specific care management]. / Amélioration du pronostic obstétrical des femmes porteuses d'un utérus distilbène par une prise en charge adaptée.

OBJECTIVE: To define the interest of a specific care management of pregnancies in patients exposed in utero to diethylstilbestrol, with the intention of reducing the number of spontaneous miscarriage and prematurity. PATIENTS AND METHODS: One hundred and three pregnancies in 49 patients exposed in utero to diethylstilbestrol were followed during a 4-year study, while establishing a specific care management of pregnancies in those women. RESULTS: Spontaneous miscarriage rate was 18.5%, among which 16.5% before 15 weeks of pregnancy and 2% after 15 weeks of pregnancy. Premature birth rate was 41.9%, among which 10.8% of great premature birth (before 32 weeks of pregnancy), 13.5% of moderate premature birth (between 32 and 36 weeks of pregnancy), and 17.6% of minor prematurity (after 36 weeks of pregnancy). The patients' average delivery term was 36 +/-3.6 weeks. DISCUSSION AND CONCLUSION: As compared with the literature data, our miscarriage and prematurity rates are found to be lower. Our specific care management seems thus to be effective.

One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial.

BACKGROUND: It has been proposed that hormonal supplementation during prolonged GnRH agonist therapy prevents hypoestrogenic side effects, including bone loss. The optimal combination for long-term treatments with safe metabolic profile remains questionable. A norprogesterone derivative, promegestone, was assessed for the first time in a double-blind trial. METHODS: Seventy-eight patients with endometriosis with rAFS (Revised American Society for Reproductive Medicine) scores of III-IV were randomly assigned to monthly leuprorelin 3.75 mg (1 year) which, after the third injection was used in combination with promegestone 0.5 mg (P) plus either estradiol placebo (PL) or estradiol 2 mg (E) per day. Bone mineral density (BMD) was determined at baseline, 6 and 12 months, and biological and clinical quarterly assessments were performed. Analysis was by the intention to treat method. RESULTS: At month 12, BMD changes from baseline were -6.1 +/- 3.7 and -4.9 +/- 4.0% in the PL-P group, at the spine and hip, respectively. This bone loss was prevented in the E-P group: -1.9 +/- 3.1 and -1.4 +/- 2.3%, respectively (P < 0.0001 inter-group comparisons). The BMD decrease in the E-P group was explained by the changes occurring during the first 6 months of treatment. There was no deleterious change in lipid parameters. Clinical improvement was observed without an inter-group difference. CONCLUSIONS: Estradiol 2 mg and promegestone 0.5 mg per day is an effective and safe add-back therapy, which can be proposed for prolonged leuprorelin treatment over 6 months in severe endometriosis.

[Oocyte and embryo quality in polycystic ovary syndrome]. / Qualité des ovocytes et embryons dans le syndrome des ovaires polykystiques.

OBJECTIVE: To compare oocyte and embryo quality in women with Polycystic Ovary Syndrome (PCOS) and in women with normal ovulation. PATIENTS AND METHODS: Forty women with PCOS underwent a total of 67 In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles. The control group consisted of women, of the same age, who underwent IVF (for tubal infertility) or ICSI (for male factor infertility) in the same period. RESULTS: The average number of oocytes recovered was higher in the PCOS group (12,1) than in the control group (9.6) as was the rate of immature oocytes (13.8% vs 5.8%; respectively). The fertilization rate was lower in PCOS patients (52% vs 61% in the controls). The cleavage rates, embryo morphology and pregnancy rates were similar in both groups. DISCUSSION AND CONCLUSIONS: Although more oocytes were recovered from PCOS patients, the number of good quality embryos, suitable for transfer or freezing was similar in the two groups as less of the oocytes were mature and the fertilization rate was lower in the PCOS group. IVF or ICSI (according to the indication) are therefore efficient in PCOS patients.

[Systematic hysteroscopy prior to in vitro fertilization]. / Hystéroscopie systématique avant fécondation in vitro.

OBJECTIVE: To evaluate the benefits of a diagnostic hysteroscopy prior to in vitro fertilization. PATIENTS AND METHODS: We retrospectively studied 145 patients who underwent ICSI during a period of 6 months. Office hysteroscopy was systematically performed before the first stimulation cycle. If pathological findings were revealed, appropriate medical or surgical treatment was given. RESULTS: Pathological patterns were observed in 45% of hysteroscopies. Endometritis, polyps and myomas and mucosal diseases were the most frequently observed. The patients aged over 38 years didn't show higher rate of pathology (29% vs 27% for the younger patients). The treatment of pathologies gave the same pregnancy rate than the normal cavities. Patients with endometritis were treated with antibiotics and 40% of them became pregnant in the following cycle. DISCUSSION AND CONCLUSION: Systematic hysteroscopy prior to IVF-ICSI showed to be an effective investigation that could improve the pregnancy rate.

[Medical treatment for recurrent miscarriages]. / Les traitements médicaux des avortements spontanés à répétition.

Effective proven therapies for recurrent abortions are few. Aspirin, prednisone and heparin are most commonly utilized but are not clearly proven to outperform expectant management except in case of antiphospholipid syndrome. Progesterone supplementation is unproven in effectiveness but of low risk. Therapeutic intervention should be strongly guided by the principle of doing no harm to the patient.

[Comparison of 2 therapeutic strategies in severe endometriosis, in young women consulting for sterility or pain. II. In the case of infertility, value of ovarian stimulation with intrauterine insemination after surgery]. / Comparaison de deux stratégies thérapeutiques dans les endométrioses sévères, chez des femmes jeunes consultant pour stérilité ou douleurs. II. En cas d'infertilité, intérêt des stimulations ovariennes avec inséminations intra-utérines après la chirurgie.

AIM OF THE STUDY: Define the best medico surgical strategy in infertile women with stage III-IV endometriosis. MATERIAL AND METHODS: Two groups, A (N26) and B (N 37), treated for infertility associated or not with pelvic pain, due to stage AFS III or IV endometriosis, were compared. They had similar surgical procedure: operative laparoscopy including resection of endometriotic lesions, more particularly endometriomas and rectovaginal septum nodules. Associated medical strategy was different: group A, operative laparoscopy without preoperative treatment and in 40% a second laparoscopy taking place after 2-3 months of LHRH analogues; no post operative treatment; group B, operative laparoscopy taking place after ovarian blockage with 3-6 weeks of Diane (Androcur + ethinyl estradiol), then 2-3 months of analogue postoperative treatment immediately followed by ovarian stimulation (OS) + intrauterine insemination (IUI) in women more than 30 years old with operative tubes (N 22), no treatment for six months in similar cases less than 30 (N 5), and IVF in women with damaged tubes (N 5) or after OS + IUI failure (N 4). One patient refused two patients with high FSH level had oocyte donation. RESULTS: Two years evolutive pregnancy rate was significantly higher (p < 0.01) in group B (59%) versus group A (23%) and was higher after OS + IUI (68%) than after IVF (55%) or without any treatment in women < 30 (43%). The difference is equally significant by age (p < 0.05), for endometriomas (p < 0.01) and for recurrences (p < 0.01). CONCLUSION: Similar results obtained for pelvic pain (see chapter I) suggest that both strategies are similarly successful in treating endometriosis. These results confirm the interest of an ART after surgery for stage III-IV endometriosis and show that OS + IUI, a less costly than IVF technique, can be used successfully in selected cases with operative tubes.

[Comparison of 2 therapeutic strategies for severe endometriosis, in young women counsulting for sterility or pain. Results in cases of chronic pelvic pain]. / Comparaison de deux stratégies thérapeutiques dans les endométrioses sévères, chez des femmes jeunes consultant pour stérilité ou douleurs. Résultats en cas de douleurs pelviennes chroniques.

AIM OF THE STUDY: Compare two medical strategies associated to surgery in women requiring for chronic pelvic pain due to stage III-IV endometriosis. MATERIAL AND METHODS: Two different patient groups, A (N 27) and B (N 41), requiring for chronic pelvic pain, associated with AFS stage III-IV endometriosis, operated on from 1992 to 1997, were compared. The medium age was 35 and 34 years, respectively. Pelvic pain, classified in three stages, was similar in both groups but they were more AFS stage IV in group A, 67% than in group B, 46% (p < 0.01). Both groups had similar operative procedure: laparoscopic resection of deep endometriotic nodules or endometriomas, plus destruction of small superficial lesions using CO2 laser (A) or bipolar coagulation (B). Associated medical strategy was different: group A: operative laparoscopy without preoperative treatment and in 25% a second laparoscopy taking place after two-three months of LHRH analogues; no postoperative treatment; group B, operative laparoscopy taking place after ovarian blockage with three-six weeks of Diane (Androcur + ethinyl estradiol), then two-three months of analogue postoperative treatment immediately followed by long term progestoid treatment in order to prevent recurrences in women without pregnancy desire. RESULTS: After one year, 6/27 (22%) of A and 3/41 (7%) of B had no follow-up. Of the followed patients, a complete improvement was observed in 18/21 (86%) A, 33/38 (87%) B, moderate pelvic pain continued in 2/21 (10%) A, 4/38 (11%) B, and the treatment was in failure in 1/21 (5%) A, 1/38 (3%) B, without significant difference. After two years, 67% of A and 76% of B had a follow-up and the corresponding rates of complete improvement are 72% (A), 87% (B), incomplete improvement: 22% (A), 10% (B) and failure: 6% (A), 3% (B). The difference is lightly significant (p < 0.05) and remains so if patients without follow-up are considered as failures. There was no persistence nor recurrence of endometriosis nor endometrioma two years after the surgery was completed. CONCLUSION: Since there were more stage IV endometriosis in group A than in B, the different medical strategies and particularly the long term postoperative treatment used in B seem have little influence on results. However, these data was obtained in women of medium age > 30, with a relatively short follow-up. It should be of interest to compare in a prospective multicentric study the long term follow-up of two cohorts of young women operated on for stage III-IV endometriosis, receiving or not a long term medical treatment after surgery in order to prevent recurrences.