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Les Collégiennes 1977, Dir. Claude Pierson DVD available Notes available Les Collégiennes alternative title for Les Collégiennes Notes available Les Friandises musclées alternative title for Hurlements de plaisir Notes available Hard Love - Le Porno adolescenti alternative title for Hurlements de plaisir Notes available Hurlements de plaisir 1976, Dir. Serge Korber as John Thomas Notes available Je suis une petite cochonne 1979, Dir. Claude Pierson Notes available (plays Miss McIntire) Muttchens Mösengestüt 1970s Notes available (plays the cook) Mutti's Mösengestüt alternative title for Muttchens Mösengestüt Notes available (plays the cook)
Paroles & Muse X alternative title for Je suis une petite cochonne Notes available (plays Miss McIntire) Paroles et muse x alternative title for Je suis une petite cochonne Notes available (plays Miss McIntire) Paroles et muse'x alternative title for Je suis une petite cochonne Notes available (plays Miss McIntire) Partouzes suédoises 1977, Dir. Claude Pierson Notes available (plays the visitor) Peccati di una vergine alternative title for Je suis une petite cochonne Notes available (plays Miss McIntire) Schule im Orgasmus-Rausch alternative title for Les Collégiennes Notes available Sex Story alternative title for Hurlements de plaisir Notes available Swedish Emmanuelle alternative title for Partouzes suédoises Notes available (plays the visitor)



A colloquial term for babies conceived as the result of IVF, "test tube babies", refers to the tube-shaped containers of glass or plastic resin, called test tubes, that are commonly used in chemistry and biology labs. However, IVF is usually performed in Petri dishes, which are both wider and shallower and often used to cultivate cultures. In a broader sense, IVF is a form of assisted reproductive technology (ART). Medical uses Indications Further information: Infertility IVF may be used to overcome female infertility when it is due to problems with the fallopian tubes, making in vivo fertilisation difficult. It can also assist in male infertility, in those cases where there is a defect in sperm quality; in such situations intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has difficulty penetrating the egg. In these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. When indicated, the use of ICSI has been found to increase the success rates of IVF. According to UK's NICE guidelines, IVF treatment is appropriate in cases of unexplained infertility for women who have not conceived after 2 years of regular unprotected sexual intercourse.[6] In women with anovulation, it may be an alternative after 7–12 attempted cycles of ovulation induction, since the latter is expensive and more easy to control.[7] Success rates IVF success rates are the percentage of all IVF procedures that result in a favourable outcome. Depending on the type of calculation used, this outcome may represent the number of confirmed pregnancies, called the pregnancy rate, or the number of live births, called the live birth rate. The success rate depends on variable factors such as maternal age, cause of infertility, embryo status, reproductive history, and lifestyle factors. Maternal age: Younger candidates of IVF are more likely to get pregnant. Women older than 41 are more likely to get pregnant with a donor egg.[8] Reproductive history: Women who have been previously pregnant are in many cases more successful with IVF treatments than those who have never been pregnant.[8] Due to advances in reproductive technology, live birth rates by cycle five of IVF have increased from 76% in 2005 to 80% in 2010 despite a reduction in the number of embryos being transferred (which decreased the multiple birth rate from 25% to 8%).[9] Live birth rate The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include miscarriage or stillbirth; multiple-order births, such as twins and triplets, are counted as one pregnancy. A 2017 summary compiled by the Society for Assisted Reproductive Technology (SART) which reports the average IVF success rates in the United States per age group using non-donor eggs compiled the following data:[10] <35 35-37 38-40 41-42 >42 Pregnancy rate (%) 47.1 40.6 30.9 18.8 7.6 Live birth rate (%) 40.5 30.2 18.7 9.1 2.9 In 2006, Canadian clinics reported a live birth rate of 27%.[11] Birth rates in younger patients were slightly higher, with a success rate of 35.3% for those 21 and younger, the youngest group evaluated. Success rates for older patients were also lower and decrease with age, with 37-year-olds at 27.4% and no live births for those older than 48, the oldest group evaluated.[12] Some clinics exceeded these rates, but it is impossible to determine if that is due to superior technique or patient selection, since it is possible to artificially increase success rates by refusing to accept the most difficult patients or by steering them into oocyte donation cycles (which are compiled separately). Further, pregnancy rates can be increased by the placement of several embryos at the risk of increasing the chance for multiples. The live birth rates using donor eggs are also given by the SART and include all age groups using either fresh or thawed eggs:[10] Fresh donor egg embryos Thawed donor egg embryos Live birth rate (%) 40.3 36.3 Because not each IVF cycle that is started will lead to oocyte retrieval or embryo transfer, reports of live birth rates need to specify the denominator, namely IVF cycles started, IVF retrievals, or embryo transfers. The SART summarised 2008–9 success rates for US clinics for fresh embryo cycles that did not involve donor eggs and gave live birth rates by the age of the prospective mother, with a peak at 41.3% per cycle started and 47.3% per embryo transfer for patients under 35 years of age. IVF attempts in multiple cycles result in increased cumulative live birth rates. Depending on the demographic group, one study reported 45% to 53% for three attempts, and 51% to 71% to 80% for six attempts.[13] Pregnancy rate Pregnancy rate may be defined in various ways. In the United States, the pregnancy rate used by the SART and the Centers for Disease Control (and appearing in the table in the Success Rates section above) are based on fetal heart motion observed in ultrasound examinations. The 2017 summary compiled by the SART the following data for the United States:[10] <35 35-37 38-40 41-42 >42 Pregnancy rate (%) 47.1 40.6 30.9 18.8 7.6 In 2006, Canadian clinics reported an average pregnancy rate of 35%.[11] A French study estimated that 66% of patients starting IVF treatment finally succeed in having a child (40% during the IVF treatment at the centre and 26% after IVF discontinuation). Achievement of having a child after IVF discontinuation was mainly due to adoption (46%) or spontaneous pregnancy (42%).[14] Miscarriage Rate According to a study done by the Mayo Clinic miscarriage rates for IVF are somewhere between 15–25%.[15] Predictors of success The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, duration of infertility or subfertility, bFSH and number of oocytes, all reflecting ovarian function.[16] Optimal woman's age is 23–39 years at time of treatment.[17] A triple-line endometrium is associated with better IVF outcomes.[18] Biomarkers that affect the pregnancy chances of IVF include: Antral follicle count, with higher count giving higher success rates.[19] Anti-Müllerian hormone levels, with higher levels indicating higher chances of pregnancy,[19] as well as of live birth after IVF, even after adjusting for age.[20] Factors of semen quality for the sperm provider. Level of DNA fragmentation[21] as measured, e.g. by Comet assay, advanced maternal age and semen quality. Women with ovary-specific FMR1 genotypes including het-norm/low have significantly decreased pregnancy chances in IVF.[22] Progesterone elevation on the day of induction of final maturation is associated with lower pregnancy rates in IVF cycles in women undergoing ovarian stimulation using GnRH analogues and gonadotrophins.[23] At this time, compared to a progesterone level below 0.8 ng/ml, a level between 0.8 and 1.1 ng/ml confers an odds ratio of pregnancy of approximately 0.8, and a level between 1.2 and 3.0 ng/ml confers an odds ratio of pregnancy of between 0.6 and 0.7.[23] On the other hand, progesterone elevation does not seem to confer a decreased chance of pregnancy in frozen–thawed cycles and cycles with egg donation.[23] Characteristics of cells from the cumulus oophorus and the membrana granulosa, which are easily aspirated during oocyte retrieval. These cells are closely associated with the oocyte and share the same microenvironment, and the rate of expression of certain genes in such cells are associated with higher or lower pregnancy rate.[24] An endometrial thickness (EMT) of less than 7 mm decreases the pregnancy rate by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified.[25] Other determinants of outcome of IVF include: As the maternal age increases, the likelihood of conception decreases[26] and the chance of miscarriage increases.[27] With increasing paternal age, especially 50 years and older, the rate of blastocyst formation decreases.[28] Tobacco smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.[29] A body mass index (BMI) over 27 causes a 33% decrease in likelihood to have a live birth after the first cycle of IVF, compared to those with a BMI between 20 and 27.[29] Also, pregnant women who are obese have higher rates of miscarriage, gestational diabetes, hypertension, thromboembolism and problems during delivery, as well as leading to an increased risk of fetal congenital abnormality.[29] Ideal body mass index is 19–30.[17] Salpingectomy or laparoscopic tubal occlusion before IVF treatment increases chances for women with hydrosalpinges.[17][30] Success with previous pregnancy and/or live birth increases chances[17] Low alcohol/caffeine intake increases success rate[17] The number of embryos transferred in the treatment cycle[31] Embryo quality Some studies also suggest that autoimmune disease may also play a role in decreasing IVF success rates by interfering with proper implantation of the embryo after transfer.[22] Aspirin is sometimes prescribed to women for the purpose of increasing the chances of conception by IVF, but as of 2016 there was no evidence to show that it is safe and effective.[32][33] A 2013 review and meta analysis of randomised controlled trials of acupuncture as an adjuvant therapy in IVF found no overall benefit, and concluded that an apparent benefit detected in a subset of published trials where the control group (those not using acupuncture) experienced a lower than average rate of pregnancy requires further study, due to the possibility of publication bias and other factors.[34] A Cochrane review came to the result that endometrial injury performed in the month prior to ovarian induction appeared to increase both the live birth rate and clinical pregnancy rate in IVF compared with no endometrial injury. There was no evidence of a difference between the groups in miscarriage, multiple pregnancy or bleeding rates. Evidence suggested that endometrial injury on the day of oocyte retrieval was associated with a lower live birth or ongoing pregnancy rate.[30] For women, intake of antioxidants (such as N-acetyl-cysteine, melatonin, vitamin A, vitamin C, vitamin E, folic acid, myo-inositol, zinc or selenium) has not been associated with a significantly increased live birth rate or clinical pregnancy rate in IVF according to Cochrane reviews.[30] The review found that oral antioxidants given to men in couples with male factor or unexplained subfertility may improve live birth rates, but more evidence is needed.[30] A Cochrane review in 2015 came to the result that there is no evidence identified regarding the effect of preconception lifestyle advice on the chance of a live birth outcome.[30] Complications Multiple births The major complication of IVF is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. Britain, Belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed IVF pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of less than 2,500 grams (5.5 lb).[35] Sex ratio distortions Certain kinds of IVF, in particular ICSI (first applied in 1991) and blastocyst transfer (first applied in 1984) have been shown to lead to distortions in the sex ratio at birth. ICSI leads to slightly more female births (51.3% female) while blastocyst transfer leads to significantly more boys (56.1% male) being born. Standard IVF done at the second or third day leads to a normal sex ratio. Epigenetic modifications caused by extended culture leading to the death of more female embryos has been theorised as the reason why blastocyst transfer leads to a higher male sex ratio, however adding retinoic acid to the culture can bring this ratio back to normal.[36] Spread of infectious disease By sperm washing, the risk that a chronic disease in the male providing the sperm would infect the female or offspring can be brought to negligible levels. In males with hepatitis B, The Practice Committee of the American Society for Reproductive Medicine advises that sperm washing is not necessary in IVF to prevent transmission, unless the female partner has not been effectively vaccinated.[37][38] In females with hepatitis B, the risk of vertical transmission during IVF is no different from the risk in spontaneous conception.[38] However, there is not enough evidence to say that ICSI procedures are safe in females with hepatitis B in regard to vertical transmission to the offspring.[38] Regarding potential spread of HIV/AIDS, Japan's government prohibited the use of IVF procedures for couples in which both partners are infected with HIV. Despite the fact that the ethics committees previously allowed the Ogikubo, Tokyo Hospital, located in Tokyo, to use IVF for couples with HIV, the Ministry of Health, Labour and Welfare of Japan decided to block the practice. Hideji Hanabusa, the vice president of the Ogikubo Hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove HIV from sperm.[39] Other risks to the egg provider/retriever A risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome, particularly if hCG is used for inducing final oocyte maturation. This results in swollen, painful ovaries. It occurs in 30% of patients. Mild cases can be treated with over the counter medications and cases can be resolved in the absence of pregnancy. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. In severe cases patients have sudden excess abdominal pain, nausea, vomiting and will result in hospitalisation. During egg retrieval, there exists a small chance of bleeding, infection, and damage to surrounding structures such as bowel and bladder (transvaginal ultrasound aspiration) as well as difficulty in breathing, chest infection, allergic reactions to medication, or nerve damage (laparoscopy). Ectopic pregnancy may also occur if a fertilised egg develops outside the uterus, usually in the fallopian tubes and requires immediate destruction of the fetus. IVF does not seem to be associated with an elevated risk of cervical cancer, nor with ovarian cancer or endometrial cancer when neutralising the confounder of infertility itself.[40] Nor does it seem to impart any increased risk for breast cancer.[41] Regardless of pregnancy result, IVF treatment is usually stressful for patients.[42] Neuroticism and the use of escapist coping strategies are associated with a higher degree of distress, while the presence of social support has a relieving effect.[42] A negative pregnancy test after IVF is associated with an increased risk for depression in women, but not with any increased risk of developing anxiety disorders.[43] Pregnancy test results do not seem to be a risk factor for depression or anxiety among men.[43] Studies show that there is an increased risk of venous thrombosis or pulmonary embolism during the first trimester of IVF.[44] When looking at long-term studies comparing women who received or did not receive IVF, there seems to be no correlation with increased risk of cardiac events. There are more ongoing studies to solidify this.[45] Spontaneous pregnancy has occurred after successful and unsuccessful IVF treatments.[46] Within 2 years of delivering an infant conceived through IVF, subfertile couples had a conception rate of 18%.[47] Birth defects A review in 2013 came to the result that infants resulting from IVF (with or without ICSI) have a relative risk of birth defects of 1.32 (95% confidence interval 1.24–1.42) compared to naturally conceived infants.[48] In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia; the mechanism of causality is unclear.[49] However, in a population-wide cohort study of 308,974 births (with 6,163 using assisted reproductive technology and following children from birth to age five) researchers found: "The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors." [50] Parental factors included known independent risks for birth defects such as maternal age, smoking status, etc. Multivariate correction did not remove the significance of the association of birth defects and ICSI (corrected odds ratio 1.57), although the authors speculate that underlying male infertility factors (which would be associated with the use of ICSI) may contribute to this observation and were not able to correct for these confounders. The authors also found that a history of infertility elevated risk itself in the absence of any treatment (odds ratio 1.29), consistent with a Danish national registry study [51] and "implicates patient factors in this increased risk." The authors of the Danish national registry study speculate: "our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants." Risk in singleton pregnancies resulting from IVF (with or without ICSI)[52] Condition Relative risk 95% confidence interval Beckwith–Wiedemann syndrome 3-4 congenital anomalies 1.67 1.33–2.09 ante-partum haemorrhage 2.49 2.30–2.69 hypertensive disorders of pregnancy 1.49 1.39–1.59 preterm rupture of membranes 1.16 1.07–1.26 Caesarean section 1.56 1.51–1.60 gestational diabetes 1.48 1.33–1.66 induction of labour 1.18 1.10–1.28 small for gestational age 1.39 1.27–1.53 preterm birth 1.54 1.47–1.62 low birthweight 1.65 1.56–1.75 perinatal mortality 1.87 1.48–2.37 Other risks to the offspring If the underlying infertility is related to abnormalities in spermatogenesis, it is plausible, but too early to examine that male offspring are at higher risk for sperm abnormalities.[clarification needed] IVF does not seem to confer any risks regarding cognitive development, school performance, social functioning, and behaviour.[53] Also, IVF infants are known to be as securely attached to their parents as those who were naturally conceived, and IVF adolescents are as well-adjusted as those who have been naturally conceived.[54] Limited long-term follow-up data suggest that IVF may be associated with an increased incidence of hypertension, impaired fasting glucose, increase in total body fat composition, advancement of bone age, subclinical thyroid disorder, early adulthood clinical depression and binge drinking in the offspring.[53][55] It is not known, however, whether these potential associations are caused by the IVF procedure in itself, by adverse obstetric outcomes associated with IVF, by the genetic origin of the children or by yet unknown IVF-associated causes.[53][55] Increases in embryo manipulation during IVF result in more deviant fetal growth curves, but birth weight does not seem to be a reliable marker of fetal stress.[56] IVF, including ICSI, is associated with an increased risk of imprinting disorders (including Prader-Willi syndrome and Angelman syndrome), with an odds ratio of 3.7 (95% confidence interval 1.4 to 9.7).[57] An IVF-associated incidence of cerebral palsy and neurodevelopmental delay are believed to be related to the confounders of prematurity and low birthweight.[53] Similarly, an IVF-associated incidence of autism and attention-deficit disorder are believed to be related to confounders of maternal and obstetric factors.[53] Overall, IVF does not cause an increased risk of childhood cancer.[58] Studies have shown a decrease in the risk of certain cancers and an increased risks of certain others including retinoblastoma,[59] hepatoblastoma[58] and rhabdomyosarcoma.[58] Method A depiction of the procedure of in-vitro fertilisation. Theoretically, IVF could be performed by collecting the contents from a woman's fallopian tubes or uterus after natural ovulation, mixing it with sperm, and reinserting the fertilised ova into the uterus. However, without additional techniques, the chances of pregnancy would be extremely small. The additional techniques that are routinely used in IVF include ovarian hyperstimulation to generate multiple eggs, ultrasound-guided transvaginal oocyte retrieval directly from the ovaries, co-incubation of eggs and sperm, as well as culture and selection of resultant embryos before embryo transfer into a uterus. Ovarian hyperstimulation Main article: Controlled ovarian hyperstimulation Ovarian hyperstimulation is the stimulation to induce development of multiple follicles of the ovaries. It should start with response prediction by e.g. age, antral follicle count and level of anti-Müllerian hormone.[60] The resulting prediction of e.g. poor or hyper-response to ovarian hyperstimulation determines the protocol and dosage for ovarian hyperstimulation.[60] Ovarian hyperstimulation also includes suppression of spontaneous ovulation, for which two main methods are available: Using a (usually longer) GnRH agonist protocol or a (usually shorter) GnRH antagonist protocol.[60] In a standard long GnRH agonist protocol the day when hyperstimulation treatment is started and the expected day of later oocyte retrieval can be chosen to conform to personal choice, while in a GnRH antagonist protocol it must be adapted to the spontaneous onset of the previous menstruation. On the other hand, the GnRH antagonist protocol has a lower risk of ovarian hyperstimulation syndrome (OHSS), which is a life-threatening complication.[60] For the ovarian hyperstimulation in itself, injectable gonadotropins (usually FSH analogues) are generally used under close monitoring. Such monitoring frequently checks the estradiol level and, by means of gynecologic ultrasonography, follicular growth. Typically approximately 10 days of injections will be necessary. Natural IVF Main article: Natural cycle in vitro fertilisation There are several methods termed natural cycle IVF:[61] IVF using no drugs for ovarian hyperstimulation, while drugs for ovulation suppression may still be used. IVF using ovarian hyperstimulation, including gonadotropins, but with a GnRH antagonist protocol so that the cycle initiates from natural mechanisms. Frozen embryo transfer; IVF using ovarian hyperstimulation, followed by embryo cryopreservation, followed by embryo transfer in a later, natural, cycle.[62] IVF using no drugs for ovarian hyperstimulation was the method for the conception of Louise Brown. This method can be successfully used when women want to avoid taking ovarian stimulating drugs with its associated side-effects. HFEA has estimated the live birth rate to be approximately 1.3% per IVF cycle using no hyperstimulation drugs for women aged between 40–42.[63] Mild IVF[64] is a method where a small dose of ovarian stimulating drugs are used for a short duration during a woman's natural cycle aimed at producing 2–7 eggs and creating healthy embryos. This method appears to be an advance in the field to reduce complications and side-effects for women and it is aimed at quality, and not quantity of eggs and embryos. One study comparing a mild treatment (mild ovarian stimulation with GnRH antagonist co-treatment combined with single embryo transfer) to a standard treatment (stimulation with a GnRH agonist long-protocol and transfer of two embryos) came to the result that the proportions of cumulative pregnancies that resulted in term live birth after 1 year were 43.4% with mild treatment and 44.7% with standard treatment.[65] Mild IVF can be cheaper than conventional IVF and with a significantly reduced risk of multiple gestation and OHSS.[66] Final maturation induction Further information: Final maturation induction When the ovarian follicles have reached a certain degree of development, induction of final oocyte maturation is performed, generally by an injection of human chorionic gonadotropin (hCG). Commonly, this is known as the "trigger shot."[67] hCG acts as an analogue of luteinising hormone, and ovulation would occur between 38 and 40 hours after a single HCG injection,[68] but the egg retrieval is performed at a time usually between 34 and 36 hours after hCG injection, that is, just prior to when the follicles would rupture. This avails for scheduling the egg retrieval procedure at a time where the eggs are fully mature. HCG injection confers a risk of ovarian hyperstimulation syndrome. Using a GnRH agonist instead of hCG eliminates most of the risk of ovarian hyperstimulation syndrome, but with a reduced delivery rate if the embryos are transferred fresh.[69] For this reason, many centers will freeze all oocytes or embryos following agonist trigger


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