(1)Approach to a case of Infertility Dr

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(1)Approach to a case of Infertility Dr. Shaheen Anjum Professor & Incharge ART Unit Department of Obstetrics & Gynaecology JN Medical College, AMU, Aligarh.

(2) OBJECTIVES • To present the recent concepts in the management of infertility • To draw clinically relevant conclusions based on: META-ANALYSIS RANDOMISED CONTROLLED TRIALS GUIDELINES AND PROTOCOLS(NICE, RCOG, ESHRE) • To discuss the best possible clinical management options with local perspective.

(3) BACKGROUND INFORMATION • About 84% of couples would conceive within one year of trying for a pregnancy. • Another 8% would conceive in the next year giving a cumulative pregnancy rate of 92% at the end of two years. • Subfertility or infertility is defined as the inability to conceive after 12 months of regular, unprotected intercourse. • The WHO estimates the overall prevalence of primary infertility in India to be between 3.9 and 16.8%..

(4) BACKGROUND INFORMATION • A woman of reproductive age who has not conceived after. 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner.. • Offer an earlier referral for specialist consultation to discuss the options for attempting conception, further assessment and appropriate treatment where – - the woman is aged 35 years or over - there is a known clinical cause of infertility or a history of predisposing factors for infertility NICE Guidelines 2013.

(5) BACKGROUND INFORMATION • The single most important determinant of a couple’s fertility is the age of the female partner: At the age of up to 25 years CCR is 60% at six months and 85% at one year At the age of 35 years or more the CCR 60% at one year and 85% at two years. is.

(6) Age: Miscarriage • Recognized – – – –. Age 30: 7-15% Age 31-34: 17-21% Age 35-39: 17-28% Age 40: 40-52%. • Unrecognized: 60%.

(7) Types of Infertility . Primary infertility Couple Has Never Produced A pregnancy . . Secondary infertility . Woman has previously been pregnant, regardless of the outcome, and now is unable to conceive Globally, most infertile couples suffer from primary infertility.

(8) Main Causes of Infertility Percentage. 33%. 22% Female factor 30%. Male Factor Combined. 40%. Unexplained.

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(10) Causes of Female infertility Percentage Ovulatory. 7% 25%. 17%. Tubal blockage Pelvic adhesions Other tubal abnormalities. 11%. 11% 11%. Endometriosis & othercauses Hormonal.

(11) EVALUATION OF INFERTILE COUPLE.

(12) • Should be seen together because both partners are affected by decisions surrounding investigation and treatment. • Should be offered counselling.

(13) Evaluating both partners is essential  Couple should be informed about:  different causes of infertility  tests and procedures required to make a diagnosis  various therapeutic possibilities  Couple’s interview is conducted together as well as separately  to obtain confidential information Richard Lord. .

(14) Step1 history: General and Sexual History . General history   . . occupation and background use of tobacco, alcohol and drugs history of abdominal surgery and earlier diseases/infections. Sexual history . . sexual disturbances or dysfunction such as vaginismus, dyspareunia or erectile dysfunction sexually transmitted infections.

(15) Obstetric and Gynecological History    .  . Reproductive history Gynecological history Age at menarche Menstrual periods: duration and intervals Previous contraceptive use Previous testing and treatment for infertility.

(16) Step2 : General and Gynecological Examination Visual evaluation and pelvic exam for women to rule out: Endocrinopathy Tumors PID Uterine hypoplasia Cervical lesions Congenital anomalies.

(17) Step -3 Basic Investigations of Infertility.

(18) Male Factor Semen analysis should be conducted as part of initial investigation The male partner should normally have two semen analyses performed during the initial investigation usually 2 to 3 weeks apart..

(19) Male Factor.

(20) Normal Semen Parametres  WHO Global reference values (fertile men) 2009: • Volume: 1.5 ml or more • pH: >7.2 • Sperm concentration: 15 million spermatozoa per ml or more • Total sperm number: 39 million spermatozoa per ejaculate or more • Motility (PR +NP%): 40% or more motile* • Vitality (%): 58 • White blood cells (106 per ml): < 1.0 • Morphology (%): 4 or more.

(21) Male Factor • If the first sperm analysis result is abnormal, the patient should be offered a repeat test from the same laboratory at least 3 months after the initial analysis • Severe abnormality (azoospermia or severe oligozoospermia) of the initial sperm sample however, warrants an immediate referral to a tertiary centre or uro-gynecologist..

(22) • Sperm function tests, screening for antisperm antibodies and postcoital tests on cervical mucus should not be offered as there is no evidence of effective treatment to improve fertility. • FSH, LH and Testosterone levels • Karyotyping and Y microdeletion test should be considered for men with non-obstructive azoospermia.

(23) Female Factor Test for Ovulation Test for tubal patency Hormonal evaluation Test for Ovarian reserve.

(24) Tests for ovulation • Basal body temperature charts and home ovulation kits should not be recommended. • Mid luteal serum progesterone levels (about 7 days before the expected menstrual cycle) • Folliculometry by TVS.

(25) Test for Tubal patency • Hysterosalpingography (HSG) • Laparoscopy and chromo-pertubation • Sono-salpingography. Nice 2013.

(26) Hormonal assessment TFT Prolactin D2/3 FSH, LH.

(27) If suspecting PCOS • 17 hydroxyprogesterone (only in the presence of clinical or biochemical evidence of hyperandrogenism) • Free/total testosterone • Fasting insulin is not necessary routinely • ACTH stimulation test if 17 hydroxyprogesterone >5nmol/L..

(28) Test for Ovarian reserve FSH >8.9 IU/L AMH < 1 ng/l AFC < 4.

(29) Tests Not Recommended • Endometrial biopsy to evaluate the luteal phase should not be performed as part of the routine investigation of the infertile couple • The postcoital test is not recommended in the routine investigation of the infertile couple. • Operative hysteroscopy should not be offered as an initial investigation • Sonosalpingography should not be offered routinely as an alternative to laparoscopy hydrotubation as their diagnostic accuracy still require further evaluation.

(30) Screening for Chlamydia trachomatis before undergoing instrumentation, If screening for Chlamydia trachomatis has not been carried out, prophylactic antibiotics should be given before uterine instrumentation.

(31) should be offered rubella susceptibility screening so that those who are susceptible to rubella can be offered rubella vaccination and be advised not to become pregnant for at least 1 month following vaccination.. Cervical screening should be offered in accordance with the national cervical screening programme guidance.

(32) When available, transvaginal ultrasound may be used as a screening test for the assessment of uterine cavity.

(33) Treatment offers hope A diagnosis of infertility does not have to mean childlessness. It can often just mean that becoming pregnant is a challenge—one that can be aided significantly by medical treatment. Today's treatments offer a good rate of success, and approximately three out of four women will get pregnant as a result of treatment..

(34) GENERAL ADVICE TO THE COUPLE • Sexual intercourse every 2-3 days • Timed intercourse to coincide with ovulation causes stress and not to be recommended • Smoking reduces both, women’s fertility as well as semen quality • Excessive alcohol is detrimental to semen quality and may cause erectile dysfunction.

(35) GENERAL ADVICE TO THE COUPLE • A body mass index of more than 29 is associated with reduced fertility in both men and women • Life style modification and especially weight reduction exercise in overweight women. • Yoga and meditation to reduce the psychological stress. • Folic acid supplement prior to conception and up to 12 weeks of conception.

(36) Unexplained infertility • Do not offer oral ovarian stimulation agents (such as clomifene citrate, anastrozole or letrozole) to women with unexplained infertility. • Inform women with unexplained infertility that clomifene citrate as a stand-alone treatment does not increase the chances of a pregnancy • Advise them to try to conceive for a total of 2 years (this can include up to 1 year before their fertility investigations) before IUI/IVF will be considered. NICE, RCOG 2013.

(37) TIMELY REFERRAL TO SPECIALIST CARE.

(38) The importance of timely referral to specialist care – It is imperative to discuss the infertility concerns with their patients in a timely manner in order to optimize their patients ability conceive. – Important discussion topics The patient desires pregnancy, What prior methods they have used to become pregnant Whether or not they are interested in pursuing (ART*) in order to achieve pregnancy, if infertility is confirmed Fertil Steril 2004;82 Suppl 1:S24-5. * assisted reproduction technologies. 38.

(39) Assisted Reproductive Techniques (ART) Any treatment that deals with “means of conception other than vaginal intercourse” is termed as ART. NICE guideline 2013.  IUI – Intra Uterine Insemination (Husband / Donor)  IVF + ET – In Vitro Fertilization + Embryo transfer  ICSI – Intra Cytoplasmic Sperm Injection.

(40) Indications for Intra Uterine Insemination (IUI) - At least one Fallopian tube must be normal and patent - Mild male infertility - Unexplained infertility - Ovulatory dysfunction, PCOS - Mild endometriosis - Cervical factors - Coital problems - Immunological factors - HIV, HBs Ag infection - Donor Sperm.

(41) Meta-Analysis of IUI • • • •. Intercourse in natural cycle Intercourse in COH cycle IUI in natural cycle IUI in COH cycles. Pregnancy Rate 2.4% 5.0% 6.5% 12.6%. Cohlen BJ et al Cochrane database Syst Rev 2003.

(42) Indication for IVF I. IVF as first line infertility treatment - Tubal pathology (severe, non-repairable) - Donor Oocyte - Genetic Surrogacy - PGD (Possibility of genetically transmitted disease) - Fertility preservation in cancer patients - Where ICSI is indicated (Azoospermia) II. IVF following failed cycles of IUI - Usually up to six cycles of IUI with controlled ovarian stimulation are recommended, but there are situations where couples should move to IVF earlier..

(43) Indicators for early referral. I. Female age - The biological clock is the major adversary to human reproduction.

(44) II. Diminished Ovarian Reserve at any age - AMH- anti-Mullerian hormone of less than or equal to 5.4pmol/l or <1ng/ml - Antral Follicle Count (AFC) – Less than or equal to 4 - Day 2/3 FSH >8.9 IU/L III. Endometriosis IV. Moderate (more than slightly abnormal) degree of semen quality abnormalities. V. Tubal Compromise NICE Guideline 2013.

(45) P0INT TO REMEMBER ONE SATISFIED PATIENT IS WORTH THOUSANDS OF GUIDELINES AND PROTOCALS.

(46) THANK YOU.

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